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Sample records for absolute treg count

  1. Eosinophil count - absolute

    MedlinePlus

    Eosinophils; Absolute eosinophil count ... the white blood cell count to give the absolute eosinophil count. ... than 500 cells per microliter (cells/mcL). Normal value ranges may vary slightly among different laboratories. Talk ...

  2. Absolute nuclear material assay using count distribution (LAMBDA) space

    SciTech Connect

    Prasad, Mano K.; Snyderman, Neal J.; Rowland, Mark S.

    2015-12-01

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  3. Absolute nuclear material assay using count distribution (LAMBDA) space

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-06-05

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  4. Flow rate calibration for absolute cell counting rationale and design.

    PubMed

    Walker, Clare; Barnett, David

    2006-05-01

    There is a need for absolute leukocyte enumeration in the clinical setting, and accurate, reliable (and affordable) technology to determine absolute leukocyte counts has been developed. Such technology includes single platform and dual platform approaches. Derivations of these counts commonly incorporate the addition of a known number of latex microsphere beads to a blood sample, although it has been suggested that the addition of beads to a sample may only be required to act as an internal quality control procedure for assessing the pipetting error. This unit provides the technical details for undertaking flow rate calibration that obviates the need to add reference beads to each sample. It is envisaged that this report will provide the basis for subsequent clinical evaluations of this novel approach. PMID:18770842

  5. Enumeration of absolute cell counts using immunophenotypic techniques.

    PubMed

    Mandy, F; Brando, B

    2001-05-01

    Absolute counting of cells or cell subsets has a number of significant clinical applications: monitoring the disease status of HIV-infected patients, enumerating residual white blood cells in leukoreduced blood products, and assessing immunodeficiency in a variety of situations. The single-platform method (flow cytometry alone) has emerged as the method of choice for absolute cell enumeration. This technology counts only the cells of interest in a precisely determined blood volume. Exact cell identification is accomplished by a logical electronic gating algorithm capable of identifying lineage-specific immunofluorescent markers. Exclusion of unwanted cells is automatic. This extensive and detailed unit presents protocols for both volumetric and flow-rate determination of residual white blood cells and of leukocyte subsets. PMID:18770719

  6. Absolute lymphocyte count is not a suitable alternative to CD4 count for determining initiation of antiretroviral therapy in fiji.

    PubMed

    Balak, Dashika A; Bissell, Karen; Roseveare, Christine; Ram, Sharan; Devi, Rachel R; Graham, Stephen M

    2014-01-01

    Introduction. An absolute lymphocyte count is commonly used as an alternative to a CD4 count to determine initiation of antiretroviral therapy for HIV-infected individuals in Fiji when a CD4 count is unavailable. Methods. We conducted a retrospective analysis of laboratory results of HIV-infected individuals registered at all HIV clinics in Fiji. Results. Paired absolute lymphocyte and CD4 counts were available for 101 HIV-infected individuals, and 96% had a CD4 count of ≤500 cells/mm(3). Correlation between the counts in individuals was poor (Spearman rank correlation r = 0.5). No absolute lymphocyte count could be determined in this population as a suitable surrogate for a CD4 count of either 350 cells/mm(3) or 500 cells/mm(3). The currently used absolute lymphocyte count of ≤2300 cells/μL had a positive predictive value of 87% but a negative predictive value of only 17% for a CD4 of ≤350 cells/mm(3) and if used as a surrogate for a CD4 of ≤500 cells/mm(3) it would result in all HIV-infected individuals receiving ART including those not yet eligible. Weight, CD4 count, and absolute lymphocyte count increased significantly at 3 months following ART initiation. Conclusions. Our findings do not support the use of absolute lymphocyte count to determine antiretroviral therapy initiation in Fiji.

  7. Predicting AIDS-related events using CD4 percentage or CD4 absolute counts

    PubMed Central

    Pirzada, Yasmin; Khuder, Sadik; Donabedian, Haig

    2006-01-01

    Background The extent of immunosuppression and the probability of developing an AIDS-related complication in HIV-infected people is usually measured by the absolute number of CD4 positive T-cells. The percentage of CD4 positive cells is a more easily measured and less variable number. We analyzed sequential CD4 and CD8 numbers, percentages and ratios in 218 of our HIV infected patients to determine the most reliable predictor of an AIDS-related event. Results The CD4 percentage was an unsurpassed predictor of the occurrence of AIDS-related events when all subsets of patients are considered. The CD4 absolute count was the next most reliable, followed by the ratio of CD4/CD8 percentages. The value of CD4 percentage over the CD4 absolute count was seen even after the introduction of highly effective HIV therapy. Conclusion The CD4 percentage is unsurpassed as a parameter for predicting the onset of HIV-related diseases. The extra time and expense of measuring the CD4 absolute count may be unnecessary. PMID:16916461

  8. Tissue Tregs.

    PubMed

    Panduro, Marisella; Benoist, Christophe; Mathis, Diane

    2016-05-20

    The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3(+)CD4(+) regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. This review focuses on so-called tissue Tregs. We first survey existing information on the phenotype, function, sustaining factors, and human equivalents of the three best-characterized tissue-Treg populations-those operating in visceral adipose tissue, skeletal muscle, and the colonic lamina propria. We then attempt to distill general principles from this body of work-as concerns the provenance, local adaptation, molecular sustenance, and targets of action of tissue Tregs, in particular.

  9. Characterizing absolute lymphocyte count profiles in dimethyl fumarate–treated patients with MS

    PubMed Central

    Chan, Andrew; Gold, Ralf; Phillips, J. Theodore; Selmaj, Krzysztof; Chang, Ih; Novas, Mark; Rana, Jitesh; Marantz, Jing L.

    2016-01-01

    Abstract Background: Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment. Methods: We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N = 2,470) to characterize ALC profiles. Results: Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm3 persisting ≥6 months. ALCs remained ≥LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs <500 mm3 persisting ≥6 months at any time. Evidence of ALC improvement following DMF discontinuation was observed. DMF efficacy was not substantially different in patients with and without lymphopenia. Conclusion: Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia. PMID:27347439

  10. Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project.

    PubMed

    Rosenthal, Elisabeth A; Makaryan, Vahagn; Burt, Amber A; Crosslin, David R; Kim, Daniel Seung; Smith, Joshua D; Nickerson, Deborah A; Reiner, Alex P; Rich, Stephen S; Jackson, Rebecca D; Ganesh, Santhi K; Polfus, Linda M; Qi, Lihong; Dale, David C; Jarvik, Gail P

    2016-09-01

    Neutrophils are a key component of innate immunity. Individuals with low neutrophil count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower absolute neutrophil count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC. PMID:27229898

  11. Elevated absolute monocyte count predicts unfavorable outcomes in patients with angioimmunoblastic T-cell lymphoma.

    PubMed

    Yang, Yu-Qiong; Liang, Jin-Hua; Wu, Jia-Zhu; Wang, Li; Qu, Xiao-Yan; Cao, Lei; Zhao, Xiao-Li; Huang, Dong-Ping; Fan, Lei; Li, Jian-Yong; Xu, Wei

    2016-03-01

    This study was aimed at investigating the prognostic significance of the absolute monocyte count (AMC) in peripheral blood in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). AMC was performed in 73 therapy-naive patients with AITL in 2 institutions during 2008-2015, and higher AMC was observed in those with extranodal sites >1, bone marrow involvement, high lactate dehydrogenase level, the EBV infection, no response to treatment and high IPI, PIT, PIAI score group. The best AMC cut-off level at diagnosis was 0.8 × 10(9)/L and the 3-year overall survival (OS) was 64% for patients with low AMC group (≤ 0.8 × 10(9)/L) compared to 10% in high AMC group (>0.8 × 10(9)/L) (P<0.001). Multivariate analysis showed that elevated AMC remained an adverse prognostic parameter. Our results suggest that AMC is an independent prognostic parameter for OS in patients with AITL, and AMC >0.8 × 10(9)/L can routinely be used to identify high-risk patients with unfavorable survival.

  12. Initial Characterization of Unequal-Length, Low-Background Proportional Counters for Absolute Gas-Counting Applications

    SciTech Connect

    Mace, Emily K.; Aalseth, Craig E.; Bonicalzi, Ricco; Day, Anthony R.; Fuller, Erin S.; Hayes, James C.; Hoppe, Eric W.; LaFerriere, Brian D.; Merriman, Jason H.; Overman, Cory T.; Seifert, Allen; Williams, Richard M.

    2013-08-31

    Abstract. Characterization of two sets of custom unequal length proportional counters is underway at Pacific Northwest National Laboratory (PNNL). These detectors will be used in measurements to determine the absolute activity concentration of gaseous radionuclides (e.g., 37Ar). A set of three detectors has been fabricated based on previous PNNL ultra-low-background proportional counters (ULBPC) designs and now operate in PNNL’s shallow underground counting laboratory. A second set of four counters has also been fabricated using clean assembly of OFHC copper components for use in an above-ground counting laboratory. Characterization of both sets of detectors is underway with measurements of background rates, gas gain, energy resolution, and shielding considerations. These results will be presented along with uncertainty estimates of future absolute gas counting measurements.

  13. Prognostic significance of the absolute monocyte counts in lung cancer patients with venous thromboembolism.

    PubMed

    Go, Se-Il; Kim, Rock Bum; Song, Haa-Na; Kang, Myoung Hee; Lee, Un Seok; Choi, Hye Jung; Jo, Wonyong; Lee, Seung Jun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Seok-Hyun; Kang, Jung-Hun; Lee, Gyeong-Won

    2015-09-01

    We investigated the clinical significance of the absolute monocyte count (AMC) as a predictor of the response to anticoagulation and survival in lung cancer patients with venous thromboembolism (VTE). We retrospectively reviewed 1707 patients with pathologically proven lung cancer who visited the hospital between July 2008 and May 2014. Among them, the clinical data of patients newly diagnosed with VTE and treated with anticoagulation were compared between the low and high AMC groups according to the median value of AMC (640/μL) at the time of VTE diagnosis. The incidence of VTE was 7.9 % during the study period. Most of the patients had non-small-cell lung cancer (82.1 %), stage IV (64.2 %), and pulmonary thromboembolism (76.1 %) and were incidentally diagnosed with VTE (76.9 %). The patients' characteristics and laboratory values were not significantly different between the low and high AMC groups. Among patients available for evaluation of the response to anticoagulation, the high AMC group was significantly more refractory to anticoagulation than the low AMC group (no response to anticoagulation, 21.7 vs. 6.8 %, respectively; p = 0.044). Additionally, the high AMC group showed worse overall survival (OS) than the low AMC group (median, 9.6 vs. 5.9 months; p = 0.038). On multivariate analysis, high AMC, low albumin, and advanced stage were independent poor prognostic factors for OS. High AMC is associated with refractoriness to anticoagulation and poor prognosis in lung cancer patients with VTE.

  14. Absolute monocyte count predicts overall survival in mantle cell lymphomas: correlation with tumour-associated macrophages.

    PubMed

    Koh, Young Wha; Shin, Su-Jin; Park, Chansik; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2014-12-01

    Mantle cell lymphoma (MCL) is characterized by a variable clinical course in which patients can experience indolent disease or frequent relapses despite a good initial response to conventional therapy. Risk stratification of MCL is most frequently performed using the MCL International Prognostic Index (MIPI). Recent studies indicate that the peripheral blood absolute monocyte count (AMC) and tumour-associated macrophages may reflect the state of the tumour microenvironment in lymphomas. The significance of AMC and tumour-associated macrophages in the clinical course of MCL is unknown. The prognostic impact of the AMC, of CD68 expression and of CD163 expression was retrospectively examined in 103 MCL samples using the receiver operating characteristic curved. Patients with an AMC ≥ 375 cells/μL at diagnosis were more likely to present with advanced-stage disease (p = 0.026), leukocytosis (p < 0.001), lymphocytosis (p = 0.01) and granulocytosis (p = 0.003). On univariate analysis, a high AMC (≥375 cells/μL) correlated with poorer overall survival (OS) (p = 0.01). Neither CD68 nor CD163 expression was significantly associated with either OS or event-free survival. Multivariate analysis showed that a high AMC was a prognostic factor for OS, independent of the MIPI [hazards ratio (HR), 1.811; 95% confidence interval, 1.018-3.223; p = 0.043]. This study demonstrates that the AMC at the time of diagnosis is an independent prognostic factor for OS in MCL, which suggests the possibility that AMC may be used in addition to the MIPI to predict outcome in patients with MCL.

  15. Pachyman treatment improves CD4+CD25+ Treg counts and serum interleukin 4 and interferon γ levels in a mouse model of Kawasaki disease.

    PubMed

    Chu, Mao-Ping; Wang, Dan; Zhang, Ying-Ying; Li, Bao-Qing; Zhou, Ai-Hua; Chen, Xi-Wen; Qian, Yan

    2012-05-01

    The aim of this study was to explore the effect of pachyman, a mushroom extract, on CD4+CD25+ regulatory T cells (Tregs), serum interleukin 4 (IL-4) and interferon γ (IFN-γ) levels in a mouse model of Kawasaki disease. Lactobacillus casei cell wall extract was diluted to 1 mg/ml in PBS and administered to mice by intraperitoneal injection to establish a model of Kawasaki disease. Sixty female mice were used in this study, 40 of which were randomly assigned to a model (normal saline by gavage, n=20) or experimental group (200 mg/kg/day pachyman by gavage, n=20). The remaining 20 mice were disease and treatment-free, and were used as the control group. Compared to the control mice, mice in the model group exhibited a significantly lower percentage of CD4+CD25+ Tregs and significantly higher serum IL-4 and IFN-γ levels (P<0.05). However, CD4+CD25+ Tregs significantly increased and IL-4 and IFN-γ levels significantly decreased in experimental mice following pachyman treatment (P<0.05). Further analysis showed a negative correlation between CD4+CD25+ Tregs and IL-4/IFN-γ levels (P<0.05). In conclusion, pachyman improves immune function in a mouse model of Kawasaki disease by upregulating CD4+CD25+ Tregs, which may inhibit the cytokine secretion of Th1 and Th2 cells. PMID:22367425

  16. Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation, disease progression and poor survival.

    PubMed

    Herishanu, Yair; Kay, Sigi; Sarid, Nadav; Kohan, Pedram; Braunstein, Rony; Rotman, Rachel; Deutsch, Varda; Ben-Ezra, Jonathan; Naparstek, Elizabeth; Perry, Chava; Katz, Ben-Zion

    2013-10-01

    Peripheral absolute monocyte count (AMC) has been reported to correlate with clinical outcome in different types of cancers. This association may relate to alteration in circulating monocytic subpopulations and tumor infiltrating macrophages. In this study we evaluated the clinical significance of peripheral AMC in 80 treatment naive patients with CLL. Measurement of AMC was based on direct morphological enumeration, due to our findings that complete blood count data may yield incorrect monocytes enumeration values in CLL. The median AMC in patients with CLL was within normal limits, however the AMC range exceeded the values of healthy individuals. The AMC trichotomized patients into 3 distinct sub-groups with different characteristics and outcomes. High AMC patients were younger and had higher absolute lymphocytes count, while patients with low AMC had prominent immune dysregulation (lower serum IgA levels, susceptibility to infections and a tendency for positive direct anti-globulin test). The low and high AMC patients had a shorter time to treatment compared to the intermediates AMC subgroups, whereas low AMC was associated with increased mortality caused by infectious complications. In conclusion, AMC quantification during the disease course classifies CLL patients into subgroups with unique clinical features and outcomes.

  17. Initial characterization of unequal-length, low-background proportional counters for absolute gas-counting applications

    NASA Astrophysics Data System (ADS)

    Mace, E. K.; Aalseth, C. E.; Bonicalzi, R.; Day, A. R.; Fuller, E. S.; Hayes, J. C.; Hoppe, E. W.; LaFerriere, B. D.; Merriman, J. H.; Overman, C. T.; Seifert, A.; Williams, R. M.

    2013-08-01

    Characterization of two sets of custom unequal length proportional counters is underway at Pacific Northwest National Laboratory (PNNL). These detectors will be used in measurements to determine the absolute activity concentration of gaseous radionuclides (e.g., 37Ar). A set of three detectors has been fabricated based on previous PNNL ultra-low-background proportional counter designs and now operate in PNNL's shallow underground counting laboratory. A second set of four counters has also been fabricated using clean assembly of Oxygen-Free High-Conductivity copper components for use in a shielded above-ground counting laboratory. Characterization of both sets of detectors is underway with measurements of background rates, gas gain, and energy resolution. These results will be presented along with a shielding study for the above-ground cave.

  18. Initial characterization of unequal-length, low-background proportional counters for absolute gas-counting applications

    SciTech Connect

    Mace, E. K.; Aalseth, C. E.; Bonicalzi, R.; Day, A. R.; Fuller, E. S.; Hayes, J. C.; Hoppe, E. W.; LaFerriere, B. D.; Merriman, J. H.; Overman, C. T.; Seifert, A.; Williams, R. M.

    2013-08-08

    Characterization of two sets of custom unequal length proportional counters is underway at Pacific Northwest National Laboratory (PNNL). These detectors will be used in measurements to determine the absolute activity concentration of gaseous radionuclides (e.g., {sup 37}Ar). A set of three detectors has been fabricated based on previous PNNL ultra-low-background proportional counter designs and now operate in PNNL's shallow underground counting laboratory. A second set of four counters has also been fabricated using clean assembly of Oxygen-Free High-Conductivity copper components for use in a shielded above-ground counting laboratory. Characterization of both sets of detectors is underway with measurements of background rates, gas gain, and energy resolution. These results will be presented along with a shielding study for the above-ground cave.

  19. Prognostic Implication of the Absolute Lymphocyte to Absolute Monocyte Count Ratio in Patients With Classical Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine or Equivalent Regimens.

    PubMed

    Vassilakopoulos, Theodoros P; Dimopoulou, Maria N; Angelopoulou, Maria K; Petevi, Kyriaki; Pangalis, Gerassimos A; Moschogiannis, Maria; Dimou, Maria; Boutsikas, George; Kanellopoulos, Alexandros; Gainaru, Gabriella; Plata, Eleni; Flevari, Pagona; Koutsi, Katerina; Papageorgiou, Loula; Telonis, Vassilios; Tsaftaridis, Panayiotis; Sachanas, Sotirios; Yiakoumis, Xanthoula; Tsirkinidis, Pantelis; Viniou, Nora-Athina; Siakantaris, Marina P; Variami, Eleni; Kyrtsonis, Marie-Christine; Meletis, John; Panayiotidis, Panayiotis; Konstantopoulos, Kostas

    2016-03-01

    Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker. PMID:26921291

  20. Prognostic Implication of the Absolute Lymphocyte to Absolute Monocyte Count Ratio in Patients With Classical Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine or Equivalent Regimens.

    PubMed

    Vassilakopoulos, Theodoros P; Dimopoulou, Maria N; Angelopoulou, Maria K; Petevi, Kyriaki; Pangalis, Gerassimos A; Moschogiannis, Maria; Dimou, Maria; Boutsikas, George; Kanellopoulos, Alexandros; Gainaru, Gabriella; Plata, Eleni; Flevari, Pagona; Koutsi, Katerina; Papageorgiou, Loula; Telonis, Vassilios; Tsaftaridis, Panayiotis; Sachanas, Sotirios; Yiakoumis, Xanthoula; Tsirkinidis, Pantelis; Viniou, Nora-Athina; Siakantaris, Marina P; Variami, Eleni; Kyrtsonis, Marie-Christine; Meletis, John; Panayiotidis, Panayiotis; Konstantopoulos, Kostas

    2016-03-01

    Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker.

  1. Procoagulant and platelet-derived microvesicle absolute counts determined by flow cytometry correlates with a measurement of their functional capacity

    PubMed Central

    Ayers, Lisa; Harrison, Paul; Kohler, Malcolm; Ferry, Berne

    2014-01-01

    Background Flow cytometry is the most commonly used technology to measure microvesicles (MVs). Despite reported limitations of this technique, MV levels obtained using conventional flow cytometry have yielded many clinically relevant findings, such as associations with disease severity and ability to predict clinical outcomes. This study aims to determine if MV enumeration by flow cytometry correlates with a measurement of their functional capacity, as this may explain how flow cytometry generates clinically relevant results. Methods One hundred samples from healthy individuals and patients with obstructive sleep apnoea were analysed by conventional flow cytometry (FACSCalibur) and by three functional MV assays: Zymuphen MP-activity in which data were given as phosphatidylserine equivalent, STA® Phospholipid Procoag Assay expressed as clotting time and Endogenous Thrombin Potential (ETP) reflecting in vitro thrombin generation. Correlations were determined by Spearman correlation. Results Absolute counts of lactadherin+ procoagulant MVs generated by flow cytometry weakly correlated with the results obtained from the Zymuphen MP-activity (r=0.5370, p<0.0001); correlated with ETP (r=0.7444, p<0.0001); negatively correlated with STA® Phospholipid Procoag Assay clotting time (−0.7872, p<0.0001), reflecting a positive correlation between clotting activity and flow cytometry. Levels of Annexin V+ procoagulant and platelet-derived MVs were also associated with functional assays. Absolute counts of MVs derived from other cell types were not correlated with the functional results. Conclusions Quantitative results of procoagulant and platelet-derived MVs from conventional flow cytometry are associated with the functional capability of the MVs, as defined by three functional MV assays. Flow cytometry is a valuable technique for the quantification of MVs from different cellular origins; however, a combination of several analytical techniques may give the most comprehensive

  2. Prognostic Impact of Absolute Lymphocyte Counts at the End of Remission Induction in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rubnitz, Jeffrey E.; Campbell, Patrick; Zhou, Yinmei; Sandlund, John T.; Jeha, Sima; Ribeiro, Raul C.; Inaba, Hiroto; Bhojwani, Deepa; Relling, Mary V.; Howard, Scott C.; Campana, Dario; Pui, Ching-Hon

    2013-01-01

    Background Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. Methods Outcomes of 399 patients ≤ 18 years of age with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children’s Research Hospital were analyzed according to ALC at the end of remission induction therapy. Results ALC ≥ 500 cell/μL was significantly more prevalent among patients with B-lineage ALL, favorable presenting features and in those who achieved minimal residual disease (MRD) negativity on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD at the end of induction (p > 0.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS of 84.2% ± 8.9% versus 97.3 ± 1.0 for patients with higher ALC (P = .036). Conclusion ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided, therapy. PMID:23456849

  3. Digital encoding of cellular mRNAs enabling precise and absolute gene expression measurement by single-molecule counting.

    PubMed

    Fu, Glenn K; Wilhelmy, Julie; Stern, David; Fan, H Christina; Fodor, Stephen P A

    2014-03-18

    We present a new approach for the sensitive detection and accurate quantitation of messenger ribonucleic acid (mRNA) gene transcripts in single cells. First, the entire population of mRNAs is encoded with molecular barcodes during reverse transcription. After amplification of the gene targets of interest, molecular barcodes are counted by sequencing or scored on a simple hybridization detector to reveal the number of molecules in the starting sample. Since absolute quantities are measured, calibration to standards is unnecessary, and many of the relative quantitation challenges such as polymerase chain reaction (PCR) bias are avoided. We apply the method to gene expression analysis of minute sample quantities and demonstrate precise measurements with sensitivity down to sub single-cell levels. The method is an easy, single-tube, end point assay utilizing standard thermal cyclers and PCR reagents. Accurate and precise measurements are obtained without any need for cycle-to-cycle intensity-based real-time monitoring or physical partitioning into multiple reactions (e.g., digital PCR). Further, since all mRNA molecules are encoded with molecular barcodes, amplification can be used to generate more material for multiple measurements and technical replicates can be carried out on limited samples. The method is particularly useful for small sample quantities, such as single-cell experiments. Digital encoding of cellular content preserves true abundance levels and overcomes distortions introduced by amplification.

  4. Digital Encoding of Cellular mRNAs Enabling Precise and Absolute Gene Expression Measurement by Single-Molecule Counting

    PubMed Central

    2014-01-01

    We present a new approach for the sensitive detection and accurate quantitation of messenger ribonucleic acid (mRNA) gene transcripts in single cells. First, the entire population of mRNAs is encoded with molecular barcodes during reverse transcription. After amplification of the gene targets of interest, molecular barcodes are counted by sequencing or scored on a simple hybridization detector to reveal the number of molecules in the starting sample. Since absolute quantities are measured, calibration to standards is unnecessary, and many of the relative quantitation challenges such as polymerase chain reaction (PCR) bias are avoided. We apply the method to gene expression analysis of minute sample quantities and demonstrate precise measurements with sensitivity down to sub single-cell levels. The method is an easy, single-tube, end point assay utilizing standard thermal cyclers and PCR reagents. Accurate and precise measurements are obtained without any need for cycle-to-cycle intensity-based real-time monitoring or physical partitioning into multiple reactions (e.g., digital PCR). Further, since all mRNA molecules are encoded with molecular barcodes, amplification can be used to generate more material for multiple measurements and technical replicates can be carried out on limited samples. The method is particularly useful for small sample quantities, such as single-cell experiments. Digital encoding of cellular content preserves true abundance levels and overcomes distortions introduced by amplification. PMID:24579851

  5. Evaluation of the FACSPresto, a New Point of Care Device for the Enumeration of CD4% and Absolute CD4+ T Cell Counts in HIV Infection

    PubMed Central

    Makadzange, Azure Tariro; Bogezi, Carola; Boyd, Kathryn; Gumbo, Anesu; Mukura, Dorinda; Matubu, Allen; Ndhlovu, Chiratidzo Ellen

    2016-01-01

    Introduction Enumeration of CD4+ T lymphocytes is important for pre-ART disease staging and screening for opportunistic infections, however access to CD4 testing in resource limited settings is poor. Point of care (POC) technologies can facilitate improved access to CD4 testing. We evaluated the analytical performance of a novel POC device the FACSPresto compared to the FACSCalibur as a reference standard and to the PIMA, a POC device in widespread use in sub-Saharan Africa. Method Specimens were obtained from 253 HIV infected adults. Venous blood samples were analyzed on the FACSPresto and the FACSCalibur, in a subset of 41 samples additional analysis was done on the PIMA. Results The absolute CD4 count results obtained on the FACSPresto were comparable to those on the FACSCalibur with low absolute (9.5cells/μl) and relative bias (3.2%). Bias in CD4% values was also low (1.06%) with a relative bias of 4.9%. The sensitivity was lower at a CD4 count threshold of ≤350cells/μl compared with ≤500cells/μl (84.9% vs. 92.8%) resulting in a high upward misclassification rate at low CD4 counts. Specificity at thresholds of ≤350cells/μl and ≤500cells/μl were 96.6% and 96.8% respectively. The PIMA had a high absolute (-68.6cells/μl) and relative bias (-10.5%) when compared with the FACSCalibur. At thresholds of ≤350cells/μl and ≤500cells/μl the sensitivity was 100% and 95.5% respectively; specificity was 85.7% and 84.2% respectively. The coefficients of repeatability were 4.13%, 5.29% and 9.8% respectively. Discussion The analytic performance of the FACSPresto against the reference standard was very good with better agreement and precision than the PIMA. The FACSPresto had comparable sensitivity at a threshold of 500 cells/μl and better specificity than the PIMA. However the FACSPresto showed reduced sensitivity at low CD4 count thresholds. Conclusion The FACSPresto can be reliably used as a POC device for enumerating absolute CD4 count and CD4% values

  6. Targeted absolute quantification of intact proteins by reversed phase liquid chromatography-mass spectrometry, charge reduced electrospray, and condensation particle counting.

    PubMed

    Adou, Kouame; Johnston, Murray V; Dykins, John L

    2012-08-21

    A novel approach involving the use of reversed phase liquid chromatography-mass spectrometry (RPLC-MS), charge reduced electrospray (CRES), and condensation particle counting (CPC) for the absolute quantification of intact proteins in liquid solutions is introduced. Under analysis conditions optimized for the quantification of select proteins within their predetermined linear ranges, a set of at least five protein standards with molecular weights (MW) spanning the dynamic ranges of both a quadrupole time-of-flight (QTOF) MS and a suitably selected RPLC column is used to generate a calibration curve of CPC detection efficiency (DE) as a function of the square root of MW. Next, the sample of interest is analyzed, and from the MS-generated MW data, the DE of each target protein is determined from the calibration curve. On the basis of MW, DE, and number concentration (molecules/unit volume), absolute quantification is achieved for each protein of interest. Application of this approach to the absolute quantification of cytochrome C (as target compound) in a commercial protein mixture is demonstrated with a deviation of 8%, a coefficient of variation (CV) of 5%, and a quantification limit of 432 fmol. For nontarget components of the mixture (ribonuclease A, holotransferrin, and apomyoglobin), the percent deviation from the stated concentrations and the CV varied from 0.20 to 23 and from 4.1 to 18, respectively. Performance of the method was further assessed by analyzing a laboratory quality control mixture comprising 0.33 μM of cytochrome C. The calculated value was 0.34 (CV: 5.1%). Universal in essence, the new technique holds strong promise for the absolute quantification of select proteins in liquid samples under conditions of good peak resolution and stable baseline.

  7. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-05-15

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  8. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2010-07-13

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  9. Chinese herbal medicine formula Gu-Ben-Fang-Xiao-Tang attenuates airway inflammation by modulating Th17/Treg balance in an ovalbumin-induced murine asthma model

    PubMed Central

    Ruan, Guiying; Tao, Baohong; Wang, Dongguo; Li, Yong; Wu, Jingyi; Yin, Genquan

    2016-01-01

    Gu-Ben-Fang-Xiao-Tang (GBFXT) is a traditional Chinese medicine formula consisting of 11 medicinal plants, which has been used in the treatment of asthma. The present study aimed to determine the protective effects and the underlying mechanisms of GBFXT on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. A total of 50 mice were randomly assigned to the following five experimental groups: Normal, model, montelukast (2.6 mg/kg), 12 g/kg GBFXT and 36 g/kg GBFXT groups. Airway responsiveness was measured using the forced oscillation technique, while differential cell count in the bronchoalveolar lavage fluid (BALF) was measured by Wright-Giemsa staining. Histological assessment was performed by hematoxylin and eosin staining, while BALF levels of Th17/Treg cytokines were measured by enzyme-linked immunosorbent assay, and the proportions of Th17 and Treg cells were evaluated by flow cytometry. The results showed that GBFXT suppressed airway hyperresponsiveness during methacholine-induced constriction, reduced the percentage of leukocytes and eosinophils, and resulted in decreased absolute neutrophil infiltration in lung tissue. In addition, GBFXT treatment significantly decreased the IL-17A cytokine level and increased the IL-10 cytokine level in the BALF. Furthermore, GBFXT significantly suppressed Th17 cells and increased Treg cells in asthmatic mice. In conclusion, the current results demonstrated that GBFXT may effectively inhibit the progression of airway inflammation in allergic asthma, partially by modulating the Th17/Treg cell balance. PMID:27588063

  10. Low absolute lymphocyte count and addition of rituximab confer high risk for interstitial pneumonia in patients with diffuse large B-cell lymphoma.

    PubMed

    Huang, Yu-Chung; Liu, Chia-Jen; Liu, Chun-Yu; Pai, Jih-Tung; Hong, Ying-Chung; Teng, Hao-Wei; Hsiao, Liang-Tsai; Chao, Ta-Chung; Gau, Jyh-Pyng; Liu, Jin-Hwang; Hsu, Hui-Chi; Chiou, Tzeon-Jye; Chen, Po-Min; Yu, Yuan-Bin; Tzeng, Cheng-Hwai

    2011-10-01

    Several small-scale studies have reported pulmonary toxicity among patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy, though whether the use of rituximab predisposes to interstitial pneumonia (IP) remains unclear. This retrospective study was intended to identify the characteristics and risk factors of IP in patients with DLBCL. Between 2000 and 2009, 529 consecutive patients with DLBCL receiving first-line tri-weekly COP- or CHOP-based chemotherapy with or without rituximab were enrolled as subjects. IP was defined as diffuse pulmonary interstitial infiltrates found on computed tomography scans in conjunction with respiratory symptoms. IP was observed in 26 patients (4.9%), six of whom were confirmed with Pneumocystis jirovecii pneumonia. The median number of chemotherapy courses before IP was four cycles. Using multivariate analysis, absolute lymphocyte count less than 1×10(9)/l at diagnosis [odds ratio (OR) 2.75, p=0.014] and the addition of rituximab to chemotherapy (OR 4.56, p=0.003) were identified as independent risk factors for IP. In conclusion, the incidence of IP is increased in patients with DLBCL receiving rituximab-containing chemotherapy. Specific subgroups with lymphopenia at diagnosis may justify close scrutiny to detect pulmonary complications. PMID:21647583

  11. iNKT cell frequency in peripheral blood of Caucasian children and adolescent: the absolute iNKT cell count is stable from birth to adulthood.

    PubMed

    Bienemann, K; Iouannidou, K; Schoenberg, K; Krux, F; Reuther, S; Feyen, O; Bienemann, K; Schuster, F; Uhrberg, M; Laws, H-J; Borkhardt, A

    2011-10-01

    Human invariant natural killer T cells (iNKT cells) are a unique population of T cells that express a semi-invariantly rearranged T cell receptor (TCR) and are involved in a variety of immunoregulatory processes. We assessed the frequency of peripheral blood iNKT cells in 64 healthy Caucasian children from 7 months to 18 years of age and five cord blood samples by flow cytometry. iNKT cells were measured as CD3(+) cells co-expressing TCRVα24 and TCRVβ11 and using the monoclonal antibody 6B11, which recognizes specifically their invariant TCR rearrangement. The absolute number of iNKT cells ranged from 86 to 10,499 (CD3(+) /TCRVα24(+) / TCRVβ11(+)) and 233 to 11,167 (CD3(+) /6B11(+)) iNKT cells per millilitre of blood. This range is stable from birth to adulthood. The relative iNKT cell count was found to be 0.003-0.71% (CD3(+) /TCRVα24/TCRVβ11) and 0.019-0.776% (CD3/6B11) of peripheral blood T cells and shows only a slight increase with age.

  12. Effect of initial absolute monocyte count on survival outcome of patients with de novo non-M3 acute myeloid leukemia.

    PubMed

    Feng, Jianhua; Zhang, Wei; Wu, Junqing; Gao, Shenmeng; Ye, Haige; Sun, Lan; Chen, Yi; Yu, Kang; Xing, Chong-Yun

    2016-11-01

    Increased absolute monocyte count (AMC) at presentation has recently been associated with clinical outcome in different types of hematological malignancies. This study aimed to assess the prognostic value of AMC on survival in 193 adult patients with de novo non-M3 acute myeloid leukemia (AML). The median AMC for all patients at diagnosis was 0.26 × 10(9)/L, with 41.4, 31.1 and 27.5% of patients showed low (<0.12 × 10(9)/L), normal (0.12-0.80 × 10(9)/L), and high AMC (>0.80 × 10(9)/L), respectively. Univariate analysis revealed that high AMC appeared as a poor prognostic factor for overall survival (OS) (p = 0.0055), but not for disease free survival (DFS) (p = 0.1195). On multivariate analysis, initial high AMC remained an independent predictor of OS (hazard ratio 2.01, p = 0.017). Our results suggest that AMC at diagnosis, which provides additional prognostic information independently from conventional factors related to patient clinical characteristics or tumor biological features, could be a novel prognostic marker for AML.

  13. Easy Absolute Values? Absolutely

    ERIC Educational Resources Information Center

    Taylor, Sharon E.; Mittag, Kathleen Cage

    2015-01-01

    The authors teach a problem-solving course for preservice middle-grades education majors that includes concepts dealing with absolute-value computations, equations, and inequalities. Many of these students like mathematics and plan to teach it, so they are adept at symbolic manipulations. Getting them to think differently about a concept that they…

  14. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury

    PubMed Central

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin

    2016-01-01

    T helper (Th) 17 cells and CD4+ CD25+ regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  15. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury.

    PubMed

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin

    2016-02-17

    T helper (Th) 17 cells and CD4(+) CD25(+) regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease.

  16. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury.

    PubMed

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin

    2016-01-01

    T helper (Th) 17 cells and CD4(+) CD25(+) regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  17. Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance.

    PubMed

    Pilat, Nina; Klaus, Christoph; Hock, Karin; Baranyi, Ulrike; Unger, Lukas; Mahr, Benedikt; Farkas, Andreas M; Wrba, Fritz; Wekerle, Thomas

    2015-01-01

    Induction of donor-specific tolerance is still considered as the "Holy Grail" in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4(+)CD25(+) in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 10(6) cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting.

  18. Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance

    PubMed Central

    Pilat, Nina; Klaus, Christoph; Hock, Karin; Baranyi, Ulrike; Unger, Lukas; Mahr, Benedikt; Farkas, Andreas M.; Wrba, Fritz; Wekerle, Thomas

    2015-01-01

    Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+ in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 106 cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting. PMID:26273682

  19. T(reg) stability: to be or not to be.

    PubMed

    Overacre, Abigail E; Vignali, Dario Aa

    2016-04-01

    Regulatory T cell (T(reg)) stability has been primarily determined by the maintained expression of the transcription factor Forkhead box P3 (Foxp3). However, T(regs) can exhibit instability while maintaining Foxp3 expression, requiring a re-examination of what defines T(reg) stability. Recent work suggests that the establishment and stability of T(regs) is mediated by a number of mechanisms besides Foxp3 expression, such as epigenetic modifications, Foxo1/3a localization, expression of Eos and signaling via Neuropilin-1. Additional studies may help to define approaches that can undermine T(reg) stability in cancer or enhance T(reg) stability in transplantation, autoimmune or inflammatory diseases and therefore have substantial therapeutic utility. In this review, we will discuss how T(reg) stability is defined and the mechanisms utilized to maintain stability.

  20. Absolute Summ

    NASA Astrophysics Data System (ADS)

    Phillips, Alfred, Jr.

    Summ means the entirety of the multiverse. It seems clear, from the inflation theories of A. Guth and others, that the creation of many universes is plausible. We argue that Absolute cosmological ideas, not unlike those of I. Newton, may be consistent with dynamic multiverse creations. As suggested in W. Heisenberg's uncertainty principle, and with the Anthropic Principle defended by S. Hawking, et al., human consciousness, buttressed by findings of neuroscience, may have to be considered in our models. Predictability, as A. Einstein realized with Invariants and General Relativity, may be required for new ideas to be part of physics. We present here a two postulate model geared to an Absolute Summ. The seedbed of this work is part of Akhnaton's philosophy (see S. Freud, Moses and Monotheism). Most important, however, is that the structure of human consciousness, manifest in Kenya's Rift Valley 200,000 years ago as Homo sapiens, who were the culmination of the six million year co-creation process of Hominins and Nature in Africa, allows us to do the physics that we do. .

  1. Treg functional stability and its responsiveness to the microenvironment

    PubMed Central

    Barbi, Joseph; Pardoll, Drew M.; Pan, Fan

    2014-01-01

    Summary Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability. PMID:24712463

  2. Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors

    PubMed Central

    Ku, Manching; Chang, Shih-En; Hernandez, Julio; Abadejos, Justin R.; Sabouri-Ghomi, Mohsen; Muenchmeier, Niklas J.; Schwarz, Anna; Valencia, Anna M.; Kirak, Oktay

    2016-01-01

    To study the development and function of “natural-arising” T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) β-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR β-chain was able to provide stronger TCR signals. This TCR-β–driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3− CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. PMID:27044095

  3. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    PubMed Central

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  4. Low white blood cell count and cancer

    MedlinePlus

    Neutropenia and cancer; Absolute neutrophil count and cancer; ANC and cancer ... A person with cancer can get a low white blood cell count from the cancer or from treatment for the cancer. Cancer may ...

  5. CD8+ Tregs in Lupus, Autoimmunity, and Beyond

    PubMed Central

    Dinesh, Ravi K; Skaggs, Brian J; Cava, Antonio La; Hahn, Bevra H.; Singh, Ram Pyare

    2010-01-01

    While CD4+CD25high regulatory T cells (Tregs) have garnered much attention for their role in the maintenance of immune homeostasis, recent findings have shown that subsets of CD8+ T cells (CD8+ Tregs) display immunoregulatory functions as well. Both CD4+ Tregs and CD8+ Tregs appear impaired in number and/or function in several autoimmune diseases and in experimental animal models of autoimmunity, suggesting the possibility of immunotherapeutic targeting of these cells for improved management of autoimmune conditions. Our group has developed a strategy to induce CD8+ Tregs in autoimmune mice through the use of a tolerogenic self-peptide, and new information has been gained on the phenotype, function and role of induced CD8+ Tregs in autoimmunity. Here we present an overview of the role and mechanisms of action of CD8+ Tregs in autoimmunity, with a special focus on lupus. We also discuss the potential role of CD8+ Tregs in other diseases, including chronic infection and cancer. PMID:20385256

  6. Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

    PubMed Central

    Falivene, Juliana; Ghiglione, Yanina; Laufer, Natalia; Eugenia Socías, María; Pía Holgado, María; Julia Ruiz, María; Maeto, Cynthia; Inés Figueroa, María; Giavedoni, Luis D.; Cahn, Pedro; Salomón, Horacio; Sued, Omar; Turk, Gabriela; Magdalena Gherardi, María

    2015-01-01

    The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection. PMID:26099972

  7. Inducing and Administering Tregs to Treat Human Disease

    PubMed Central

    Perdigoto, Ana Luisa; Chatenoud, Lucienne; Bluestone, Jeffrey A.; Herold, Kevan C.

    2016-01-01

    Regulatory T cells (Tregs) control unwanted immune responses, including those that mediate tolerance to self as well as to foreign antigens. Their mechanisms of action include direct and indirect effects on effector T cells and important functions in tissue repair and homeostasis. Tregs express a number of cell surface markers and transcriptional factors that have been instrumental in defining their origins and potentially their function. A number of immune therapies, such as rapamycin, IL-2, and anti-T cell antibodies, are able to induce Tregs and are being tested for their efficacy in diverse clinical settings with exciting preliminary results. However, a balance exists with the use of some, such as IL-2, that may have effects on unwanted populations as well as promoting expansion and survival of Tregs requiring careful selection of dose for clinical use. The use of cell surface markers has enabled investigators to isolate and expand ex vivo Tregs more than 500-fold routinely. Clinical trials have begun, administering these expanded Tregs to patients as a means of suppressing autoimmune and alloimmune responses and potentially inducing immune tolerance. Studies in the future are likely to build on these initial technical achievements and use combinations of agents to improve the survival and functional capacity of Tregs. PMID:26834735

  8. FOXP3+ Treg Cells and Gender Bias in Autoimmune Diseases

    PubMed Central

    Nie, Jia; Li, Yang Yang; Zheng, Song Guo; Tsun, Andy; Li, Bin

    2015-01-01

    CD4+CD25+ regulatory T (Treg) cells play a pivotal role in the maintenance of immune homeostasis, where the X-linked master transcription factor forkhead box P3 (FOXP3) determines Treg cell development and function. Genetic deficiency of foxp3 induces dysfunction of Treg cells and immuno-dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome in humans. Functionally deficient Treg cells or the development of exTreg cells positively correlate with autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), and ankylosing spondylitis (AS). In general, females are more susceptible to SLE and MS but less susceptible to AS, where the expression of FOXP3 and its protein complex are perturbed by multiple factors, including hormonal fluctuations, inflammatory cytokines, and danger signals. Therefore, it is critical to explore the potential molecular mechanisms involved and these differences linked to gender. Here, we review recent findings on the regulation of FOXP3 activity in Treg cells and also discuss gender difference in the determination of Treg cell function in autoimmune diseases. PMID:26441996

  9. Ex vivo expansion of human Tregs specific for alloantigens presented directly or indirectly

    PubMed Central

    Veerapathran, Anandharaman; Pidala, Joseph; Beato, Francisca; Yu, Xue-Zhong

    2011-01-01

    Adoptive transfer of regulatory T cells (Tregs) prevents GVHD in experimental animals. Because antigen activation drives Treg function, we measured the frequency, growth requirements, and function of alloantigen-specific (allospecific) Tregs from human blood. When alloantigen was presented directly, the precursor frequency of allo-specific Tregs in normal individuals was 1.02% (95% confidence interval [95% CI]: 0.65-1.59) and non-Tregs 1.56% (95% CI: 0.94-2.55). When alloantigen was presented indirectly, the frequency of specific Tregs was approximately 100-fold less. Purified Tregs were expanded with APCs, rapamycin, IL-2, and IL-15. In 12 days, allo-specific Tregs expanded 793-fold (95% CI: 480-1107), with duplication approximately every 24 hours. Purified allo-specific Tregs suppressed responses to specific alloantigen selectively and were approximately 100-fold more potent than polyspecific Tregs and nonexpanded Tregs. Allo-specific Tregs maintained high expression of Foxp3, Bcl-2, lymphoid homing receptor CD62L, and chemokine receptor CCR7, predicting sustained function and migration to lymphoid tissues in vivo. Allo-specific Tregs produced TGF-β and IL-10 and expressed more cytoplasmic CTLA-4 compared with non-Tregs. These data provide a platform for the selective expansion of Tregs against major and possibly minor histocompatibility antigens and predict the feasibility of adoptive immunotherapy trials using Tregs with indirect allo-recognition for preventing GVHD while sparing GVL effects. PMID:21948174

  10. Counting carbohydrates

    MedlinePlus

    Carb counting; Carbohydrate-controlled diet; Diabetic diet; Diabetes-counting carbohydrates ... Many foods contain carbohydrates (carbs), including: Fruit and fruit juice Cereal, bread, pasta, and rice Milk and milk products, soy milk Beans, legumes, ...

  11. Cell counting.

    PubMed

    Phelan, M C; Lawler, G

    2001-05-01

    This unit presents protocols for counting cells using either a hemacytometer or electronically using a Coulter counter. Cell counting with a hemacytometer permits effective discrimination of live from dead cells using trypan blue exclusion. In addition, the procedure is less subject to errors arising from cell clumping or size heterogeneity. Counting cells is more quickly and easily performed using an electronic counter, but live-dead discrimination is unreliable. Cell populations containing large numbers of dead cells and/or cell clumps are difficult to count accurately. In addition, electronic counting requires resetting of the instrument for cell populations of different sizes; heterogeneous populations can give rise to inaccurate counts, and resting and activated cells may require counting at separate settings. In general, electronic cell counting is best performed on fresh peripheral blood cells. PMID:18770655

  12. Teaching Absolute Value Meaningfully

    ERIC Educational Resources Information Center

    Wade, Angela

    2012-01-01

    What is the meaning of absolute value? And why do teachers teach students how to solve absolute value equations? Absolute value is a concept introduced in first-year algebra and then reinforced in later courses. Various authors have suggested instructional methods for teaching absolute value to high school students (Wei 2005; Stallings-Roberts…

  13. Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases.

    PubMed

    Keijzer, Chantal; van der Zee, Ruurd; van Eden, Willem; Broere, Femke

    2013-01-01

    Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation and the observed side effects of these therapies illustrate the pressing need for more specific interventions. Regulatory T-cells (Treg) are pivotal controllers of (auto-aggressive) immune responses and inflammation, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Therefore, Treg became frequently studied targets for more specific immunotherapy. Especially antigen-specific targeting of Treg would enable local and tailor made interventions, while obviating the negative side effect of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for antigen-specific interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory-site. In this perspective heat shock proteins (Hsp) have several characteristics that make them highly attractive targets for antigen-specific Treg inducing therapy. The development of an antigen-specific Treg inducing vaccine is a major novel goal in the field of immunotherapy in autoimmune diseases. However, progress is hampered not only by the lack of effective antigens, but also by the fact that other factors such as dose, route, and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to the effective induction of Treg. In addition, the use of a Treg inducing adjuvant might be required to achieve an effective regulatory response, in the case of ongoing inflammation. Future goals in clinical trials will be the optimization of natural Treg expansion (or

  14. Tregs and kidney: From diabetic nephropathy to renal transplantation.

    PubMed

    Dousdampanis, Periklis; Trigka, Kostantina; Mouzaki, Athanasia

    2016-09-24

    Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs. PMID:27683634

  15. Tregs and kidney: From diabetic nephropathy to renal transplantation.

    PubMed

    Dousdampanis, Periklis; Trigka, Kostantina; Mouzaki, Athanasia

    2016-09-24

    Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs.

  16. Erythropoietin regulates Treg cells in asthma through TGFβ receptor signaling.

    PubMed

    Wan, Guoshi; Wei, Bing

    2015-01-01

    Asthma is a chronic inflammatory disorder of the airways, the development of which is suppressed by regulatory T cells (Treg). Erythropoietin (EPO) is originally defined as a hematopoietic growth factor. Recently, the anti-inflammatory effects of EPO in asthma have been acknowledged. However, the underlying mechanisms remain ill-defined. Here, we showed that EPO treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice, seemingly through promoting Foxp3-mediated activation of Treg cells in OVA-treated mouse lung. The activation of Treg cells resulted from increases in transforming growth factor β1 (TGFβ1), which were mainly produced by M2 macrophages (M2M). In vitro, Co-culture with M2M increased Foxp3 levels in Treg cells and the Treg cell number, in a TGFβ receptor signaling dependent manner. Moreover, elimination of macrophages abolished the therapeutic effects of EPO in vivo. Together, our data suggest that EPO may increase M2M, which activate Treg cells through TGFβ receptor signaling to mitigate the severity of asthma.

  17. Erythropoietin regulates Treg cells in asthma through TGFβ receptor signaling

    PubMed Central

    Wan, Guoshi; Wei, Bing

    2015-01-01

    Asthma is a chronic inflammatory disorder of the airways, the development of which is suppressed by regulatory T cells (Treg). Erythropoietin (EPO) is originally defined as a hematopoietic growth factor. Recently, the anti-inflammatory effects of EPO in asthma have been acknowledged. However, the underlying mechanisms remain ill-defined. Here, we showed that EPO treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice, seemingly through promoting Foxp3-mediated activation of Treg cells in OVA-treated mouse lung. The activation of Treg cells resulted from increases in transforming growth factor β1 (TGFβ1), which were mainly produced by M2 macrophages (M2M). In vitro, Co-culture with M2M increased Foxp3 levels in Treg cells and the Treg cell number, in a TGFβ receptor signaling dependent manner. Moreover, elimination of macrophages abolished the therapeutic effects of EPO in vivo. Together, our data suggest that EPO may increase M2M, which activate Treg cells through TGFβ receptor signaling to mitigate the severity of asthma. PMID:26807178

  18. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

    PubMed Central

    Wen, Zhenke; Shimojima, Yasuhiro; Shirai, Tsuyoshi; Li, Yinyin; Ju, Jihang; Yang, Zhen; Tian, Lu; Goronzy, Jörg J.

    2016-01-01

    Immune aging results in progressive loss of both protective immunity and T cell–mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive CD8+CCR7+ Tregs, a defect that is even more pronounced in the age-related vasculitic syndrome giant cell arteritis. In young, healthy individuals, CD8+CCR7+ Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis. PMID:27088800

  19. Tregs and kidney: From diabetic nephropathy to renal transplantation

    PubMed Central

    Dousdampanis, Periklis; Trigka, Kostantina; Mouzaki, Athanasia

    2016-01-01

    Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs. PMID:27683634

  20. Tregs and kidney: From diabetic nephropathy to renal transplantation

    PubMed Central

    Dousdampanis, Periklis; Trigka, Kostantina; Mouzaki, Athanasia

    2016-01-01

    Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs.

  1. The relation of plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) with HPV persistence in HIV-infected and HIV-uninfected women.

    PubMed

    Strickler, Howard D; Martinson, Jeffrey; Desai, Seema; Xie, Xianhong; Burk, Robert D; Anastos, Kathryn; Massad, L Stewart; Minkoff, Howard; Xue, Xiaonan; D'Souza, Gypsyamber; Levine, Alexandra M; Colie, Christine; Watts, D Heather; Palefsky, Joel M; Landay, Alan

    2014-02-01

    Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.

  2. Nanotechnology as a New Therapeutic Approach to Prevent the HIV-Infection of Treg Cells

    PubMed Central

    Jaramillo-Ruiz, Didiana; De La Mata, Francisco Javier; Gómez, Rafael; Correa-Rocha, Rafael; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Background HIV-1 has proved to infect regulatory T cells (Treg) modifying their phenotype and impairing their suppressive capacity. As Treg cells are a crucial component in the preservation of the immune homeostasis, we researched that the antiviral capacity of carboxilan dendrimers prevents the HIV-1 infection of Treg and their effects. The phenotype and suppressive capacity of Treg treated or non-treated with carbosilane dendrimers were studied by flow cytometry. Treated and non-treated Treg from healthy donors were infected with HIV-1NL4.3. The infection of Treg cells by HIV-1, and protective effect of two dendrimers were determined by measuring antigen p24gag in the supernatant of the culture and intracellular. Results The Treg cells were treated with cationic and anionic carbosilane dendrimers. The results showed that both dendrimers did not modify the phenotype and functionality of Treg cells compared with non- treated Treg cells. Anionic dendrimers showed high biocompatibility with normal activity of the Treg cells and in antiviral assays. These dendrimers were highly active against HIV-1 preventing the infection of Treg, and were able to protect the Treg from the Foxp3 downregulation induced by the HIV-1 infection. Conclusions This is the first work showing that the in vitro use of anionic dendrimers prevent the HIV-1 replication and the infection of expanded Treg cells in culture, which raises the possibility to use Treg cells therapeutically in HIV-1-infected subjects. PMID:26785250

  3. Rapid Rebound of the Treg Compartment in DEREG Mice Limits the Impact of Treg Depletion on Mycobacterial Burden, but Prevents Autoimmunity

    PubMed Central

    Varela, Filipa; Behrends, Jochen; Swallow, Maxine; Kruse, Friederike; Krull, Freyja; Ghorbani, Peyman; Mayer, Christian T.

    2014-01-01

    The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3+ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity

  4. Tregs Are Regulated by Cytokines: Implications for Autoimmunity

    PubMed Central

    La Cava, Antonio

    2008-01-01

    Several immune cell subsets contribute to the maintenance of peripheral tolerance by taking active participation in the networks that suppress autoreactive immune responses. There is ample evidence that CD4+CD25+Foxp3+ regulatory T cells (Tregs) can have an important role in suppressing the production of autoimmune responses in animal models and in humans. This review describes the influences that specific cytokines have on the differentiation, maintenance and survival of Tregs, and how these effects can ultimately directly influence both number and functional activity of these cells in autoimmune disease. PMID:18771756

  5. Multiplicity Counting

    SciTech Connect

    Geist, William H.

    2015-12-01

    This set of slides begins by giving background and a review of neutron counting; three attributes of a verification item are discussed: 240Pueff mass; α, the ratio of (α,n) neutrons to spontaneous fission neutrons; and leakage multiplication. It then takes up neutron detector systems – theory & concepts (coincidence counting, moderation, die-away time); detector systems – some important details (deadtime, corrections); introduction to multiplicity counting; multiplicity electronics and example distributions; singles, doubles, and triples from measured multiplicity distributions; and the point model: multiplicity mathematics.

  6. Reticulocyte count

    MedlinePlus

    ... radiation therapy, or infection) Cirrhosis of the liver Anemia caused by low iron levels, or low levels of vitamin B12 or folate Chronic kidney disease Reticulocyte count may be higher during pregnancy.

  7. Tower counts

    USGS Publications Warehouse

    Woody, Carol Ann; Johnson, D.H.; Shrier, Brianna M.; O'Neal, Jennifer S.; Knutzen, John A.; Augerot, Xanthippe; O'Neal, Thomas A.; Pearsons, Todd N.

    2007-01-01

    Counting towers provide an accurate, low-cost, low-maintenance, low-technology, and easily mobilized escapement estimation program compared to other methods (e.g., weirs, hydroacoustics, mark-recapture, and aerial surveys) (Thompson 1962; Siebel 1967; Cousens et al. 1982; Symons and Waldichuk 1984; Anderson 2000; Alaska Department of Fish and Game 2003). Counting tower data has been found to be consistent with that of digital video counts (Edwards 2005). Counting towers do not interfere with natural fish migration patterns, nor are fish handled or stressed; however, their use is generally limited to clear rivers that meet specific site selection criteria. The data provided by counting tower sampling allow fishery managers to determine reproductive population size, estimate total return (escapement + catch) and its uncertainty, evaluate population productivity and trends, set harvest rates, determine spawning escapement goals, and forecast future returns (Alaska Department of Fish and Game 1974-2000 and 1975-2004). The number of spawning fish is determined by subtracting subsistence, sport-caught fish, and prespawn mortality from the total estimated escapement. The methods outlined in this protocol for tower counts can be used to provide reasonable estimates ( plus or minus 6%-10%) of reproductive salmon population size and run timing in clear rivers. 

  8. A TNFR2-Agonist Facilitates High Purity Expansion of Human Low Purity Treg Cells.

    PubMed

    He, Xuehui; Landman, Sija; Bauland, Stijn C G; van den Dolder, Juliette; Koenen, Hans J P M; Joosten, Irma

    2016-01-01

    Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plus anti-CD28 monoclonal antibody (mAb) stimulation in the presence of rhIL-2, with or without rapamycin. However, the resultant Treg population is often heterogeneous and pro-inflammatory cytokines like IFNγ and IL-17A can be produced. Hence, it is crucial to search for expansion protocols that not only maximize ex vivo Treg proliferative rates, but also maintain Treg stability and preserve their suppressive function. Here, we show that ex vivo expansion of low purity magnetic bead isolated Treg in the presence of a TNFR2 agonist mAb (TNFR2-agonist) together with rapamycin, results in a homogenous stable suppressive Treg population that expresses FOXP3 and Helios, shows low expression of CD127 and hypo-methylation of the FOXP3 gene. These cells reveal a low IL-17A and IFNγ producing potential and hardly express the chemokine receptors CCR6, CCR7 and CXCR3. Restimulation of cells in a pro-inflammatory environment did not break the stability of this Treg population. In a preclinical humanized mouse model, the TNFR2-agonist plus rapamycin expanded Treg suppressed inflammation in vivo. Importantly, this Treg expansion protocol enables the use of less pure, but more easily obtainable cell fractions, as similar outcomes were observed using either FACS-sorted or MACS-isolated Treg. Therefore, this protocol is of great interest for the ex vivo expansion of Treg for clinical immunotherapy. PMID:27224512

  9. A TNFR2-Agonist Facilitates High Purity Expansion of Human Low Purity Treg Cells

    PubMed Central

    Landman, Sija; Bauland, Stijn C. G.; van den Dolder, Juliette

    2016-01-01

    Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plus anti-CD28 monoclonal antibody (mAb) stimulation in the presence of rhIL-2, with or without rapamycin. However, the resultant Treg population is often heterogeneous and pro-inflammatory cytokines like IFNγ and IL-17A can be produced. Hence, it is crucial to search for expansion protocols that not only maximize ex vivo Treg proliferative rates, but also maintain Treg stability and preserve their suppressive function. Here, we show that ex vivo expansion of low purity magnetic bead isolated Treg in the presence of a TNFR2 agonist mAb (TNFR2-agonist) together with rapamycin, results in a homogenous stable suppressive Treg population that expresses FOXP3 and Helios, shows low expression of CD127 and hypo-methylation of the FOXP3 gene. These cells reveal a low IL-17A and IFNγ producing potential and hardly express the chemokine receptors CCR6, CCR7 and CXCR3. Restimulation of cells in a pro-inflammatory environment did not break the stability of this Treg population. In a preclinical humanized mouse model, the TNFR2-agonist plus rapamycin expanded Treg suppressed inflammation in vivo. Importantly, this Treg expansion protocol enables the use of less pure, but more easily obtainable cell fractions, as similar outcomes were observed using either FACS-sorted or MACS-isolated Treg. Therefore, this protocol is of great interest for the ex vivo expansion of Treg for clinical immunotherapy. PMID:27224512

  10. Restoring host-microbe homeostasis via selective chemoattraction of Tregs.

    PubMed

    Garlet, G P; Sfeir, C S; Little, S R

    2014-09-01

    The disruption of host-microbe homeostasis at the site of periodontal disease is considered a key factor for disease initiation and progress. While the downstream mechanisms responsible for the tissue damage per se are relatively well-known (involving various patterns of immune response operating toward periodontal tissue destruction), we are only beginning to understand the complexity of host-microbe interactions in the periodontal environment. Unfortunately, most of the research has been focused on the disruption of host-microbe homeostasis instead of focusing on the factors responsible for maintaining homeostasis. In this context, regulatory T-cells (Tregs) comprise a CD4+FOXp3 +T-cell subset with a unique ability to regulate other leukocyte functions to avoid excessive immune activation and its pathological consequences. Tregs act as critical determinants of host-microbe homeostasis, as well as determinants of a balanced host response after the disruption of host-microbe homeostasis by pathogens. In periodontitis, Tregs play a protective role, with their natural recruitment being responsible for conversion of active into inactive lesions. With controlled-release technology, it is now possible to achieve a selective chemoattraction of Tregs to periodontal tissues, attenuating experimental periodontitis evolution due to the local control of inflammatory immune response and the generation of a pro-reparative environment.

  11. NKT cells, Treg, and their interactions in bone marrow transplantation

    PubMed Central

    Kohrt, Holbrook E.; Pillai, Asha B.; Lowsky, Robert; Strober, Samuel

    2010-01-01

    Bone marrow transplantation (BMT) is a potentially curative treatment for patients with leukemia and lymphoma. Tumor eradication is promoted by the anti-tumor activity of donor T cells contained in the transplant; however, donor T cells also mediate the serious side effect of graft-versus-host disease (GVHD). Separation of GVHD from graft anti-tumor activity is an important goal of research in improving transplant outcome. One approach is to take advantage of the immunomodulatory activity of regulatory NKT cells and CD4+ CD25+ Treg of host and/or donor origin. Both host and donor NKT cells and donor Treg are able to prevent GVHD in murine models. In this review, we summarize the mechanisms of NKT cell- and Treg-mediated protection against GVHD in mice while maintaining graft anti-tumor activity. In addition, we also examine the interactions between NKT cells and Treg in the context of BMT, and integrate the data from murine experimental models with the observations made in humans. PMID:20583031

  12. Depletion of Fat Tregs Prevents Age-Associated Insulin Resistance

    PubMed Central

    Bapat, Sagar P.; Suh, Jae Myoung; Fang, Sungsoon; Liu, Sihao; Zhang, Yang; Cheng, Albert; Zhou, Carmen; Liang, Yuqiong; LeBlanc, Mathias; Liddle, Christopher; Atkins, Annette R.; Yu, Ruth T.; Downes, Michael; Evans, Ronald M.; Zheng, Ye

    2015-01-01

    Age-associated insulin resistance (IR) and obesity-associated IR are two physiologically distinct forms of adult onset diabetes. While macrophage-driven inflammation is a core driver of obesity-associated IR1–6, the underlying mechanisms of the obesity-independent yet highly prevalent age-associated IR7 are largely unexplored. Comparative adipo-immune profiling (AIP) reveals that fat-resident regulatory T cells, termed fTregs, accumulate in adipose tissue as a function of age, but not obesity. Supporting the existence of two distinct mechanisms underlying IR, mice deficient in fTregs are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. In contrast, selective depletion of fTregs via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. These findings establish that distinct immune cell populations within adipose tissue underlie aging- and obesity-associated IR and implicate fTregs as adipo-immune drivers and potential therapeutic targets in the treatment of age-associated IR. PMID:26580014

  13. Women Count

    NASA Astrophysics Data System (ADS)

    Hurley, Dana M.

    2014-11-01

    I am a counter by nature. I count things as an effective way to occupy my mind. How many people are in this room? How many are women? How many are wearing glasses? How many people are using a Mac versus a PC?

  14. Counting Populations

    ERIC Educational Resources Information Center

    Damonte, Kathleen

    2004-01-01

    Scientists use sampling to get an estimate of things they cannot easily count. A population is made up of all the organisms of one species living together in one place at the same time. All of the people living together in one town are considered a population. All of the grasshoppers living in a field are a population. Scientists keep track of the…

  15. Counting Penguins.

    ERIC Educational Resources Information Center

    Perry, Mike; Kader, Gary

    1998-01-01

    Presents an activity on the simplification of penguin counting by employing the basic ideas and principles of sampling to teach students to understand and recognize its role in statistical claims. Emphasizes estimation, data analysis and interpretation, and central limit theorem. Includes a list of items for classroom discussion. (ASK)

  16. Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

    PubMed Central

    Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

    2012-01-01

    Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

  17. [Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia].

    PubMed

    Szerafin, László; Jakó, János; Riskó, Ferenc

    2015-04-01

    Bevezetés: Az alacsony perifériás lymphocyta- és magas monocytaszám kedvezőtlen prognózisra utal különböző típusú lymphomákban és egyéb daganatos megbetegedésekben. Krónikus lymphoid leukaemiában azonban az abszolút monocytaszám prognosztikus értékéről csak kevés adat ismert. Célkitűzés: A szerzők krónikus lymphoid leukaemiás betegeik diagnóziskor mért abszolút monocytaszámának hatását vizsgálták a kezelésig eltelt időre és a túlélésre. Módszer: 2005. január 1. és 2012. december 31. között diagnosztizált 223 krónikus lymphoid leukaemiás beteg adatait rögzítették. Értékelték a kezelést igénylő betegek arányát, a kezelésig eltelt idő és a túlélés relatív kockázatát, valamint a halálokokat a Rai-stádiumtól függően, a CD38-, ZAP-70-pozitivitásnak és az abszolút monocytaszámnak megfelelően. Eredmények: Rai 0, I., II., III. és IV. stádiumban a betegek 21,1%-a, 57,4%-a, 88,9%-a, 88,9%-a és 100%-a, CD38-, illetve ZAP-70-pozitivitás esetén a betegek 61,9%-a, illetve 60,8%-a, továbbá, ha az abszolút monocytaszámuk <0,25 G/l, 0,25–0,75 G/l és >0,75 G/l volt, akkor a betegek 76,9%-a, 21,2%-a és 66,2%-a szorult kezelésre. A kezelés elkezdéséig tartó medián idő, illetve a túlélés medián ideje a monocytaszámtól függően 19,5, 65 és 35,5 hónap, illetve 41,5, 65 és 49,5 hónap volt. A kezelésmegkezdés szükségességének relatív kockázata, RR = 1,62 (p<0,01) volt a 0,25 G/l alatti vagy 0,75 G/l feletti és a 0,25–0,75 G/l abszolút monocytaszámú betegek összehasonlításakor, míg a túlélésé RR = 2,41 (p<0,01) volt, ha a 0,25 G/l alatti és feletti abszolút monocytaszámú betegeket hasonlították össze. A relatív kockázatok Rai 0 stádiumú betegekben vizsgálva is szignifikánsak maradtak. A fő halálokok alacsony abszolút monocytaszám esetén fertőzések (41,7%) és a krónikus lymphoid leukaemia (58,3%), míg közepes és magas monocytaszámnál elsősorban egyéb daganatok (25,9% és 35,3%) és egyéb kórokok (48,1% és 11,8%) voltak. Következtetések: Az alacsony és a magas abszolút monocytaszámú betegek kezeléséig eltelt időtartam rövidebb, mint a köztes alcsoportba tartozóké. Az alacsony abszolút monocytaszám – a fertőzéses szövődmények és a krónikus lymphoid leukaemia miatt – megnövekedett halálozással társul. Az abszolút monocytaszám Rai 0 stádiumban is többlet prognosztikus információt tud adni. Orv. Hetil., 2015, 156(15), 592–597.

  18. Absolute neutrophil values in malignant patients on cytotoxic chemotherapy.

    PubMed

    Madu, A J; Ibegbulam, O G; Ocheni, S; Madu, K A; Aguwa, E N

    2011-01-01

    A total of eighty patients with various malignancies seen between September 2008 and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed of various malignancies, consisting of Breast cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%), Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1 (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil count was done using Turks solution and improved Neubauer counting chamber and Galen 2000 Olympus microscope. The socio demographic data of the patients were assessed from a questionnaire. There were 27 males (33.75%) and 53 females (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The mean absolute neutrophil count of the respondents pre-and post chemotherapy was 3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were significant differences in both the absolute neutrophil count (p=0.00) compared to the pre-chemotherapy values. Chemotherapeutic combinations containing cyclophosphamide and Adriamycin were observed to cause significant reduction in absolute neutrophil.

  19. Absolute biological needs.

    PubMed

    McLeod, Stephen

    2014-07-01

    Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb 'need' has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind-dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of 'normative' are distinguished. On two of these, to describe a phenomenon or claim as 'normative' is to describe it as value-dependent. A description of a phenomenon or claim as 'normative' in the third sense does not entail such value-dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses. PMID:23586876

  20. Absolute biological needs.

    PubMed

    McLeod, Stephen

    2014-07-01

    Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb 'need' has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind-dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of 'normative' are distinguished. On two of these, to describe a phenomenon or claim as 'normative' is to describe it as value-dependent. A description of a phenomenon or claim as 'normative' in the third sense does not entail such value-dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses.

  1. Dendritic cells decreased the concomitant expanded Tregs and Tregs related IL-35 in cytokine-induced killer cells and increased their cytotoxicity against leukemia cells.

    PubMed

    Pan, Ying; Tao, Qianshan; Wang, Huiping; Xiong, Shudao; Zhang, Rui; Chen, Tianping; Tao, Lili; Zhai, Zhimin

    2014-01-01

    Regulatory T cells (Tregs) are potent immunosuppressive cells and essential for inducing immune tolerance. Recent studies have reported that Tregs and Tregs related cytokines can inhibit the antitumor activity of cytokine-induced killer (CIK) cells, but dendritic cells co-cultured CIK (DC-CIK) cells can be used for induction of a specific immune response by blocking of Tregs and TGF-β, IL-10. As a novel identified cytokine, IL-35 is specially produced by Tregs and plays an essential role in immune regulation. However, it remains unknown whether IL-35 roles in tumor immunotherapy mediated by CIK and DC-CIK cells. In this study, we cultured CIK and DC-CIK cells from the same healthy adult samples, and investigated their phenotype, proliferation, cytotoxic activity against leukemia cell lines K562 and NB4 by FCM and CCK-8, measured IL-35, TGF-β and IL-10 protein by ELISA, detected Foxp3, IL-35 and IL-35 receptor mRNA by Real-time PCR, respectively. We found Tregs and IL-35 concomitantly expanded by a time-dependent way during the generation of CIK cells, but DC significantly down-regulated the expression of them and simultaneously up-regulated the proliferation ability as well as cytotoxic activity of CIK cells against leukemia cell lines. Therefore, our data suggested that DC decreased concomitant expanded Tregs and Tregs related IL-35 in CIK cells and might contribute to improve their cytotoxicity against leukemia cells in vitro.

  2. Novel Foxo1–dependent transcriptional programs control Treg cell function

    PubMed Central

    Ouyang, Weiming; Liao, Will; Luo, Chong T.; Yin, Na; Huse, Morgan; Kim, Myoungjoo V.; Peng, Min; Chan, Pamela; Ma, Qian; Mo, Yifan; Meijer, Dies; Zhao, Keji; Rudensky, Alexander Y.; Atwal, Gurinder; Zhang, Michael Q.; Li, Ming O.

    2013-01-01

    Regulatory T (Treg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses1–4. Foxp3 operates as a late-acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6–10. However, whether Foxo proteins act beyond the Treg-cell-commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulatorof Treg cell function. Treg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with Treg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt–Foxo1 signalling module controls a novel genetic program indispensable for Treg cell function. PMID:23135404

  3. Glycogen synthase kinase 3β inhibition promotes human iTreg differentiation and suppressive function.

    PubMed

    Xia, Yongxiang; Zhuo, Han; Lu, Yunjie; Deng, Lei; Jiang, Runqiu; Zhang, Long; Zhu, Qin; Pu, Liyong; Wang, Xuehao; Lu, Ling

    2015-05-01

    Induced regulatory T cells (iTregs) are essential to maintain immunological tolerance, immune homeostasis and prevention of autoimmunity. Some studies suggest that glycogen synthase kinase 3β (GSK3β) is involved in the mouse iTreg differentiation; however, whether GSK3β inhibits or enhances iTreg differentiation is still a matter of controversy. To address this issue, we have utilized human naïve CD4(+) T cells and investigated whether GSK3 activity changes during iTreg differentiation and whether altering GSK3 activity influences the development of iTregs and its suppressive function. As a constitutively activated kinase, during iTreg differentiation GSK3β became quickly deactivated (phosphorylated at serine 9), which is dependent on MAPK pathway rather than PI3-kinase/Akt pathway. Our results indicated that inhibition of GSK3β by specific inhibitors, SB216763 or TDZD-8, promoted the differentiation of iTreg and increased their suppressive activity. In contrast, overexpression of GSK3β significantly inhibited iTreg differentiation. Furthermore, GSK3β inhibition enhanced iTreg differentiation through the TGF-β/Smad3 pathway. Taken together, this study demonstrates that inhibition of GSK3β enhances human iTreg differentiation and its suppressive activity, and provides a rationale to target GSK3β as a novel immunotherapeutic strategy.

  4. Characterization of regulatory T cell (Treg) function in patients infected with Leishmania braziliensis.

    PubMed

    Costa, Diego L; Guimarães, Luiz H; Cardoso, Thiago M; Queiroz, Adriano; Lago, Ednaldo; Roselino, Ana M; Bacellar, Olívia; Carvalho, Edgar M; Silva, João S

    2013-12-01

    Th1 immune responses are crucial for eliminating Leishmania parasites. However, despite strong Th1 responses, cutaneous leishmaniasis (CL) patients infected with Leishmania braziliensis develop the disease, while milder Th1 responses are found in sub-clinical (SC) infections. Therefore, CL patients may experience impaired regulatory T cell (Treg) function, causing excessive Th1 responses and tissue damage. To address this hypothesis, we characterized the function of circulating Tregs in L. braziliensis infected CL patients and compared them to Tregs from uninfected controls (UC) and SC subjects. The frequency of circulating Tregs was similar in CL patients, UC and SC subjects. Moreover, CL patients Tregs suppressed lymphocyte proliferation and PBMC pro-inflammatory cytokine production more efficiently than UC Tregs, and also produced higher levels of IL-10 than UC and SC Tregs. Furthermore, PBMC and mononuclear cells from lesions of CL patients responded normally to Treg-induced suppression. Therefore, the lesion development in CL patients infected with L. braziliensis is not associated with impairment in Treg function or failure of cells to respond to immunomodulation. Rather, the increased Treg activation in CL patients may impair parasite elimination, resulting in establishment of chronic infection. Thus, immunological strategies that interfere with this response may improve leishmaniasis treatment.

  5. Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3+ Treg cells

    PubMed Central

    Verhagen, Johan; Wraith, David C.

    2014-01-01

    Adoptive transfer of antigen-specific, in vitro-induced Foxp3+ Treg (iTreg) cells protects against autoimmune disease. To generate antigen-specific iTreg cells at high purity, however, remains a challenge. Whereas polyclonal T cell stimulation with anti-CD3 and anti-CD28 antibody yields Foxp3+ iTreg cells at a purity of 90–95%, antigen-induced iTreg cells typically do not exceed a purity of 65–75%, even in a TCR-transgenic model. In a similar vein to thymic Treg cell selection, iTreg cell differentiation is influenced not only by antigen recognition and the availability of TGF-β but also by co-factors including costimulation and adhesion molecules. In this study, we demonstrate that blockade of the T cell integrin Leukocyte Function-associated Antigen-1 (LFA-1) during antigen-mediated iTreg cell differentiation augments Foxp3 induction, leading to approximately 90% purity of Foxp3+ iTreg cells. This increased efficacy not only boosts the yield of Foxp3+ iTreg cells, it also reduces contamination with activated effector T cells, thus improving the safety of adoptive transfer immunotherapy. PMID:25108241

  6. Reticulocyte Count Test

    MedlinePlus

    ... Reticulocyte Count Related tests: Red Blood Cell Count ; Hemoglobin ; Hematocrit ; Complete Blood Count ; Blood Smear ; Erythropoietin ; Vitamin ... on a complete blood count (CBC) , RBC count , hemoglobin or hematocrit , to help determine the cause To ...

  7. White Blood Cell Count

    MedlinePlus

    ... Home Visit Global Sites Search Help? White Blood Cell Count Share this page: Was this page helpful? Also ... Leukocyte Count; White Count Formal name: White Blood Cell Count Related tests: Complete Blood Count , Blood Smear , White ...

  8. The absolute path command

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it canmore » provide the absolute path to a relative directory from the current working directory.« less

  9. The absolute path command

    SciTech Connect

    Moody, A.

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it can provide the absolute path to a relative directory from the current working directory.

  10. Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces.

    PubMed

    Nakahashi-Oda, Chigusa; Udayanga, Kankanam Gamage Sanath; Nakamura, Yoshiyuki; Nakazawa, Yuta; Totsuka, Naoya; Miki, Haruka; Iino, Shuichi; Tahara-Hanaoka, Satoko; Honda, Shin-ichiro; Shibuya, Kazuko; Shibuya, Akira

    2016-04-01

    Epithelial tissues continually undergo apoptosis. Commensal organisms that inhabit the epithelium influence tissue homeostasis, in which regulatory T cells (Treg cells) have a central role. However, the physiological importance of epithelial cell apoptosis and how the number of Treg cells is regulated are both incompletely understood. Here we found that apoptotic epithelial cells negatively regulated the commensal-stimulated proliferation of Treg cells. Gut commensals stimulated CX3CR1(+)CD103(-)CD11b(+) dendritic cells (DCs) to produce interferon-β (IFN-β), which augmented the proliferation of Treg cells in the intestine. Conversely, phosphatidylserine exposed on apoptotic epithelial cells suppressed IFN-β production by the DCs via inhibitory signaling mediated by the cell-surface glycoprotein CD300a and thus suppressed Treg cell proliferation. Our findings reveal a regulatory role for apoptotic epithelial cells in maintaining the number of Treg cell and tissue homeostasis. PMID:26855029

  11. Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia.

    PubMed

    Wu, Hao; Li, Peng; Shao, Na; Ma, Jingjing; Ji, Min; Sun, Xiulian; Ma, Daoxin; Ji, Chunyan

    2012-05-01

    Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and the development of myeloid cells and their precursors in the blood and bone marrow. Interleukin 35 (IL-35), a novel inhibitory cytokine secreted by regulatory T (Treg) cells is a novel potential target used for the therapeutic manipulation of Treg activity in order to treat cancer and autoimmune diseases. To investigate the role and imbalance of Treg-related cytokines in the pathogenesis of AML, we measured the plasma concentration of three Treg-associated cytokines [IL-35, IL-10 and transforming growth factor-β (TGF-β)] and evaluated their clinical relevance. The concentration of IL-35, IL-10 and TGF-β in plasma specimens from 55 patients with AML [27 newly diagnosed (ND) patients and 28 in complete remission (CR)] and 24 controls was analyzed using the enzyme-linked immunosorbent assay method. Significantly higher levels of plasma IL-35 and IL-10 were observed in AML ND patients compared with healthy controls or AML CR patients. IL-10 concentrations were positively correlated with TGF-β, whereas no correlations were found between the other cytokines. IL-10 levels were positively correlated with white blood cell (WBC) and neutrophil (NEU) count but there were no correlations between IL-35 and TGF-β with WBC and NEU count. In conclusion, we demonstrated for the first time that AML ND patients have increased plasma concentrations of IL-35, suggesting that this cytokine is involved in the pathophysiological process of the disease, and that further research is required to address this issue.

  12. Disturbed Th17/Treg Balance in Patients with Non-small Cell Lung Cancer.

    PubMed

    Duan, Min-Chao; Han, Wei; Jin, Pei-Wen; Wei, Yu-Ping; Wei, Qiu; Zhang, Liang-Ming; Li, Jun-Chen

    2015-12-01

    The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction. The concentrations of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-23, and transforming growth factor-beta (TGF-β1) were also measured by enzyme-linked immunosorbent assay analysis (ELISA). The frequency of circulating Th17 cells and Treg cells was increased in samples derived from patients with NSCLC, accompanied by the upregulation of Foxp3 and RORγt. However, a negative correlation between Treg cells and Th17 cells was found in patients with NSCLC. Additionally, the Th17/Treg ratio and the related cytokines were also significantly higher in patients with NSCLC than in healthy controls. Furthermore, the frequency of Th17 cells was positively correlated with IL-1β, IL-6, and IL-23 in patients with NSCLC, and the frequency of Treg cells was positively correlated with TGF-β1 and IL-10. More importantly, the Th17/Treg ratio was positively correlated with the CEA concentrations in patients with NSCLC. Our data indicated that Th17 and Treg subset are involved in the immunopathology of NSCLC. Distinct cytokine environment might play a key role in the differentiation of the Th17 and Treg cells in NSCLC. Reconstituting an adequate balance between Th17 and Treg may be beneficial in the treatment of NSCLC.

  13. mTORC1 couples immune signals and metabolic programming to establish Treg cell function

    PubMed Central

    Zeng, Hu; Yang, Kai; Cloer, Caryn; Neale, Geoffrey; Vogel, Peter; Chi, Hongbo

    2013-01-01

    The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct T cell fate decisions1. Activation of mTOR, comprised of mTORC1 and mTORC2 complexes, delivers an obligatory signal for proper activation and differentiation of effector CD4+ T cells2,3, whereas in the regulatory T cell (Treg) compartment, the Akt-mTOR axis is widely acknowledged as a crucial negative regulator of Treg de novo differentiation4–8 and population expansion9. However, whether mTOR signaling affects the homeostasis and function of Tregs remains largely unexplored. Here we show that mTORC1 signaling is a pivotal positive determinant of Treg function. Tregs have elevated steady-state mTORC1 activity compared to naïve T cells. Signals via T cell receptor (TCR) and IL-2 provide major inputs for mTORC1 activation, which in turn programs suppressive function of Tregs. Disruption of mTORC1 through Treg-specific deletion of the essential component Raptor leads to a profound loss of Treg suppressive activity in vivo and development of a fatal early-onset inflammatory disorder. Mechanistically, Raptor/mTORC1 signaling in Tregs promotes cholesterol/lipid metabolism, with the mevalonate pathway particularly important for coordinating Treg proliferation and upregulation of suppressive molecules CTLA-4 and ICOS to establish Treg functional competency. In contrast, mTORC1 does not directly impact the expression of Foxp3 or anti- and pro-inflammatory cytokines in Tregs, suggesting a non-conventional mechanism for Treg functional regulation. Lastly, we provide evidence that mTORC1 maintains Treg function partly through inhibiting the mTORC2 pathway. Our results demonstrate that mTORC1 acts as a fundamental ‘rheostat’ in Tregs to link immunological signals from TCR and IL-2 to lipogenic pathways and functional fitness, and highlight a central role of metabolic programming of Treg suppressive activity in immune

  14. Characterization of Th17 and FoxP3(+) Treg Cells in Paediatric Psoriasis Patients.

    PubMed

    Zhang, L; Li, Y; Yang, X; Wei, J; Zhou, S; Zhao, Z; Cheng, J; Duan, H; Jia, T; Lei, Q; Huang, J; Feng, C

    2016-03-01

    Psoriasis is one of the most common inflammatory skin conditions affecting both children and adults. Growing evidence indicates that T-helper 17 (Th17) cells and CD4(+) CD25(+) regulatory T (Treg) cells play an important role in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in paediatric psoriasis remain unclear. In this study, we found that both Th17 and FoxP3(+) Treg cells and the ratio of Th17 to Treg cell frequency in the peripheral circulation were increased in patients with paediatric psoriasis and were positively correlated with the disease severity. The function of Treg to suppress CD4(+) CD25(-) T cell proliferation and IFN-γ secretion was impaired during the onset of psoriasis. After disease remission, both the Th17 and Treg cell frequencies were decreased, and the suppressive function of the Treg cells was obviously restored. However, neither Treg cells from the disease onset nor those after remission can regulate IL-17 secretion by CD4(+) T cells. These findings will further our understanding of the associations between Th17 and Treg cells in paediatric psoriasis and their influence on disease severity.

  15. HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection

    PubMed Central

    Kared, Hassen; Lelièvre, Jean-Daniel; Donkova-Petrini, Vladimira; Aouba, Albertine; Melica, Giovanna; Balbo, Michèle; Weiss, Laurence; Lévy, Yves

    2008-01-01

    Objective Expansion of Regulatory T (Treg) cells has been described in chronically HIV-infected subjects. We investigated whether HIV-suppressive Treg could be detected during primary HIV infection (PHI). Methods Seventeen patients diagnosed early after PHI (median: 13 days; 1–55) were studied. Median CD4 cell count was 480 cells/μl (33–1306) and plasma HIV RNA levels ranged between 3.3 to 5.7 log10 cp/mL. Suppressive capacity of blood purified CD4+CD25+ was evaluated in a co-culture assay. Fox-p3, IL-2 and IL-10 were quantified by RT-PCR and intra-cellular staining of ex vivo and activated CD4+CD25high T cells. Results The frequency of CD4+CD127lowCD25high T cells among CD4 T cells was lower in PHI compared to chronic patients (n=19). They exhibited a phenotype of memory T cells and expressed constitutively FoxP3. Similarly to chronic patients, Treg from PHI patients inhibited the proliferation of PPD and HIV p24 activated CD4+CD25− T cells. CD4+CD25high T cells from PHI patients responded specifically to p24 stimulation by expressing IL-10. In untreated PHI patients, the frequency, as well as HIV-specific activity of Treg decreased during a 24-month follow up. A positive correlation between percentages of Treg and both CD4 cell counts and the magnitude of p24-specific suppressive activity at diagnosis of PHI was found. Conclusions Our data showed that HIV drives Treg since PHI and that these cells persist throughout the course of the infection. A correlation between the frequency of Treg and CD4 T cell counts suggest that these cells may impact on the immune activation set point at PHI diagnosis. PMID:19005268

  16. Metabolic control of the Treg/Th17 axis

    PubMed Central

    Barbi, Joseph; Pardoll, Drew; Pan, Fan

    2012-01-01

    Summary The interplay of the immune system with other aspects of physiology is continually being revealed and in some cases studied in considerable mechanistic detail. A prime example is the influence of metabolic cues on immune responses. It is well appreciated that upon activation, T cells take on a metabolic profile profoundly distinct from that of their quiescent and anergic counterparts; however, a number of recent breakthroughs have greatly expanded our knowledge of how aspects of cellular metabolism can shape a T-cell response. Particularly important are findings that certain environmental cues can tilt the delicate balance between inflammation and immune tolerance by skewing T-cell fate decisions toward either the T-helper 17 (Th17) or T-regulatory (Treg) cell lineage. Recognizing the unappreciated immune modifying potential of metabolic factors and particularly those involved in the generation of these functionally opposing T-cell subsets will likely add new and potent therapies to our repertoire for treating immune mediated pathologies. In this review, we summarize and discuss recent findings linking certain metabolic pathways, enzymes, and byproducts to shifts in the balance between Th17 and Treg cell populations. These advances highlight numerous opportunities for immune modulation. PMID:23405895

  17. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice

    PubMed Central

    Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

  18. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice.

    PubMed

    Yan, Chao; Zhang, Bei-Bei; Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

  19. MHC-derived allopeptide activates TCR-biased CD8+ Tregs and suppresses organ rejection

    PubMed Central

    Picarda, Elodie; Bézie, Séverine; Venturi, Vanessa; Echasserieau, Klara; Mérieau, Emmanuel; Delhumeau, Aurélie; Renaudin, Karine; Brouard, Sophie; Bernardeau, Karine; Anegon, Ignacio; Guillonneau, Carole

    2014-01-01

    In a rat heart allograft model, preventing T cell costimulation with CD40Ig leads to indefinite allograft survival, which is mediated by the induction of CD8+CD45RClo regulatory T cells (CD8+CD40Ig Tregs) interacting with plasmacytoid dendritic cells (pDCs). The role of TCR-MHC-peptide interaction in regulating Treg activity remains a topic of debate. Here, we identified a donor MHC class II–derived peptide (Du51) that is recognized by TCR-biased CD8+CD40Ig Tregs and activating CD8+CD40Ig Tregs in both its phenotype and suppression of antidonor alloreactive T cell responses. We generated a labeled tetramer (MHC-I RT1.Aa/Du51) to localize and quantify Du51-specific T cells within rat cardiac allografts and spleen. RT1.Aa/Du51-specific CD8+CD40Ig Tregs were the most suppressive subset of the total Treg population, were essential for in vivo tolerance induction, and expressed a biased, restricted Vβ11-TCR repertoire in the spleen and the graft. Finally, we demonstrated that treatment of transplant recipients with the Du51 peptide resulted in indefinite prolongation of allograft survival. These results show that CD8+CD40Ig Tregs recognize a dominant donor antigen, resulting in TCR repertoire alterations in the graft and periphery. Furthermore, this allopeptide has strong therapeutic activity and highlights the importance of TCR-peptide-MHC interaction for Treg generation and function. PMID:24789907

  20. BRG1-mediated immune tolerance: facilitation of Treg activation and partial independence of chromatin remodelling

    PubMed Central

    Chaiyachati, Barbara H; Jani, Anant; Wan, Yisong; Huang, Haichang; Flavell, Richard; Chi, Tian

    2013-01-01

    Treg activation in response to environmental cues is necessary for regulatory T cells (Tregs) to suppress inflammation, but little is known about the transcription mechanisms controlling Treg activation. We report that despite the known proinflammatory role of the chromatin-remodelling factor BRG1 in CD4 cells, deleting Brg1 in all αβ T cell lineages led to fatal inflammation, which reflected essential roles of BRG1 in Tregs. Brg1 deletion impaired Treg activation, concomitant with the onset of the inflammation. Remarkably, as the inflammation progressed, Tregs became increasingly activated, but the activation levels could not catch up with the severity of inflammation. In vitro assays indicate that BRG1 regulates a subset of TCR target genes including multiple chemokine receptor genes. Finally, using a method that can create littermates bearing either a tissue-specific point mutation or deletion, we found the BRG1 ATPase activity partially dispensable for BRG1 function. Collectively, these data suggest that BRG1 acts in part via remodelling-independent functions to sensitize Tregs to inflammatory cues, thus allowing Tregs to promptly and effectively suppress autoimmunity. PMID:23321680

  1. Driving allotolerance: CAR-expressing Tregs for tolerance induction in organ and stem cell transplantation.

    PubMed

    Edinger, Matthias

    2016-04-01

    Regulatory T cells (Tregs) modulate the function of a variety of immune cells and are critical for maintaining self-tolerance and preventing the development of autoimmune disease. Due to their ability to suppress effector T cells, Tregs have been increasingly explored for clinical use to suppress alloresponses. While this approach has been promising in preclinical models and early clinical trials, widespread clinical use of Tregs has been limited by the low number of these cells in the periphery and the unknown frequency of allo-responsive Tregs. In this issue of the JCI, MacDonald and colleagues transduced human Tregs with a chimeric antigen receptor (CAR) that targets the HLA class I molecule A2. These CAR-expressing T cells were readily activated via CAR stimulation and exerted potent immunosuppressive effects when stimulated in vitro. In a murine model of hematopoietic stem cell transplantation, CAR-modified Tregs were more effective in preventing the development of graft-versus-host disease compared with polyclonal Tregs. The results of this study lay the groundwork for the further evaluation of CAR-expressing Tregs in the prevention or treatment of transplant complications. PMID:26999608

  2. Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice

    PubMed Central

    Serr, Isabelle; Fürst, Rainer W.; Achenbach, Peter; Scherm, Martin G.; Gökmen, Füsun; Haupt, Florian; Sedlmeier, Eva-Maria; Knopff, Annette; Shultz, Leonard; Willis, Richard A.; Ziegler, Anette-Gabriele; Daniel, Carolin

    2016-01-01

    Immune tolerance is executed partly by Foxp3+regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3+Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3+Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4+T cells and demonstrate efficient human insulin-specific Foxp3+Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2Rα and TIGIT and can efficiently suppress effector T cells. Such Foxp3+Treg-induction does not trigger any effector T cells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3+Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D. PMID:26975663

  3. Affinity for self antigen selects Treg cells with distinct functional properties.

    PubMed

    Wyss, Lena; Stadinski, Brian D; King, Carolyn G; Schallenberg, Sonja; McCarthy, Nicholas I; Lee, Jun Young; Kretschmer, Karsten; Terracciano, Luigi M; Anderson, Graham; Surh, Charles D; Huseby, Eric S; Palmer, Ed

    2016-09-01

    The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities. PMID:27478940

  4. Measurement of Disintegration Rates and Absolute {gamma}-ray Intensities

    SciTech Connect

    DeVries, Daniel J.; Griffin, Henry C.

    2006-03-13

    The majority of practical radioactive materials decay by modes that include {gamma}-ray emission. For questions of 'how much' or 'how pure', one must know the absolute intensities of the major radiations. We are using liquid scintillation counting (LSC) to measurements of disintegration rates, coupled with {gamma}-ray spectroscopy to measure absolute {gamma}-ray emission probabilities. Described is a study of the 227Th chain yielding absolute {gamma}-ray intensities with {approx}0.5% accuracy and information on LSC efficiencies.

  5. Absolute radiometric calibration of the Thematic Mapper

    NASA Technical Reports Server (NTRS)

    Slater, P. N.; Biggar, S. F.; Holm, R. G.; Jackson, R. D.; Mao, Y.

    1986-01-01

    Calibration data for the solar reflective bands of the Landsat-5 TM obtained from five in-flight absolute radiometric calibrations from July 1984-November 1985 at White Sands, New Mexico are presented and analyzed. Ground reflectance and atmospheric data were utilized to predict the spectral radiance at the entrance pupil of the TM and the average number of digital counts in each TM band. The calibration of each of the TM solar reflective bands was calculated in terms of average digital counts/unit spectral radiance for each band. It is observed that for the 12 reflectance-based measurements the rms variation from the means as a percentage of the mean is + or - 1.9 percent; for the 11 measurements in the IR bands, it is + or - 3.4 percent; and the rms variation for all 23 measurements is + or - 2.8 percent.

  6. ABSOLUTE POLARIMETRY AT RHIC.

    SciTech Connect

    OKADA; BRAVAR, A.; BUNCE, G.; GILL, R.; HUANG, H.; MAKDISI, Y.; NASS, A.; WOOD, J.; ZELENSKI, Z.; ET AL.

    2007-09-10

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy Of {Delta}P{sub beam}/P{sub beam} < 5%. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detectors and was installed in the RHIC-ring in 2004. This system features proton-proton elastic scattering in the Coulomb nuclear interference (CNI) region. Precise measurements of the analyzing power A{sub N} of this process has allowed us to achieve {Delta}P{sub beam}/P{sub beam} = 4.2% in 2005 for the first long spin-physics run. In this report, we describe the entire set up and performance of the system. The procedure of beam polarization measurement and analysis results from 2004-2005 are described. Physics topics of AN in the CNI region (four-momentum transfer squared 0.001 < -t < 0.032 (GeV/c){sup 2}) are also discussed. We point out the current issues and expected optimum accuracy in 2006 and the future.

  7. Absolute Equilibrium Entropy

    NASA Technical Reports Server (NTRS)

    Shebalin, John V.

    1997-01-01

    The entropy associated with absolute equilibrium ensemble theories of ideal, homogeneous, fluid and magneto-fluid turbulence is discussed and the three-dimensional fluid case is examined in detail. A sigma-function is defined, whose minimum value with respect to global parameters is the entropy. A comparison is made between the use of global functions sigma and phase functions H (associated with the development of various H-theorems of ideal turbulence). It is shown that the two approaches are complimentary though conceptually different: H-theorems show that an isolated system tends to equilibrium while sigma-functions allow the demonstration that entropy never decreases when two previously isolated systems are combined. This provides a more complete picture of entropy in the statistical mechanics of ideal fluids.

  8. Altered connexin 43 expression underlies age dependent decrease of Treg cell suppressor function in NOD mice

    PubMed Central

    Kuczma, Michal; Wang, Cong-Yi; Ignatowicz, Leszek; Gourdie, Robert; Kraj, Piotr

    2015-01-01

    Type I diabetes (T1D) is one of the most extensively studied autoimmune diseases but the cellular and molecular mechanisms leading to T cell-mediated destruction of insulin-producing β-cells are still not well understood. Here we show that Treg cells in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Treg cells in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in Treg cells and restore the ability of conventional CD4+ T cells to upregulate Foxp3 and generate peripherally derived Treg cells. Moreover, we demonstrate that suppression mediated by Treg cells from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction-mediated intercellular communication as an important component of the Treg cell suppression mechanism compromised in NOD mice and suggests how Treg mediated immune regulation can be improved. PMID:25911751

  9. Cysticerci Drive Dendritic Cells to Promote In Vitro and In Vivo Tregs Differentiation

    PubMed Central

    Adalid-Peralta, Laura; Arce-Sillas, Asiel; Fragoso, Gladis; Cárdenas, Graciela; Rosetti, Marcos; Casanova-Hernández, Didier; Rangel-Escareño, Claudia; Uribe-Figueroa, Laura; Fleury, Agnes; Sciutto, Edda

    2013-01-01

    Regulatory T cells (Tregs) play a crucial role in immune homeostasis. Treg induction is a strategy that parasites have evolved to modulate the host's inflammatory environment, facilitating their establishment and permanence. In human Taenia solium neurocysticercosis (NC), the concurrence of increased peripheral and central Treg levels and their capacity to inhibit T cell activation and proliferation support their role in controlling neuroinflammation. This study is aimed at identifing possible mechanisms of Treg induction in human NC. Monocyte-derived dendritic cells (DC) from healthy human donors, cocultivated with autologous CD4+ naïve cells either in the presence or absence of cysticerci, promoted CD25highFoxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. Moreover, an augmentation of suppressive-related molecules (SLAMF1, B7-H1, and CD205) was found in parasite-induced DC differentiation. Increased Tregs and a higher in vivo DC expression of the regulatory molecules SLAMF1 and CD205 in NC patients were also found. SLAMF1 gene was downregulated in NC patients with extraparenchymal cysticerci, exhibiting higher inflammation levels than patients with parenchymal parasites. Our findings suggest that cysticerci may modulate DC to favor a suppressive environment, which may help parasite establishment, minimizing the excessive inflammation, which may lead to tissue damage. PMID:23762101

  10. T-cell count

    MedlinePlus

    Thymus derived lymphocyte count; T-lymphocyte count; T cell count ... T cells are a type of lymphocyte. Lymphocytes are white blood cells. They make up part of the immune system. T cells help the body fight diseases or harmful ...

  11. Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

    PubMed

    Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

    2013-01-01

    A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

  12. Absolute neutrino mass measurements

    SciTech Connect

    Wolf, Joachim

    2011-10-06

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2{beta}) searches, single {beta}-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy.Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium {beta}-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope ({sup 137}Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R and D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2{beta} decay and single {beta}-decay.

  13. Analysis of subsets of B cells, Breg, CD4Treg and CD8Treg cells in adult patients with primary selective IgM deficiency

    PubMed Central

    Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2016-01-01

    Primary selective IgM deficiency (SIGMD) is a rare and recently IUIS-recognized primary immunodeficiency disease with increased susceptibility to infections, allergy, and autoimmune diseases. The pathogenesis of selective IgM remains unclear. The objective of the study was to understand the pathogenesis of selective IgM deficiency via a comprehensive analysis of subsets of B cells, naïve and memory subsets of CD4+ and CD8+ T cells, and Breg, CD4Treg, and CD8Treg cells. Twenty adult patients with SIGMD (serum IgM 4 mg/dl-32 mg/dl) and age-and gender-matched healthy controls were studied. Naïve B cells, transitional B cells, marginal zone B cells, germinal center B cells, IgM memory B cells, switched memory B cells, plasmablasts, CD21low B cells, B1 cells, CXCR3+ naive and memory B cells; naïve, central memory, and effector memory subsets of CD4+ and CD8+ T cells, and CD4Treg, CD8Treg and Breg were phenotypically analyzed using multicolor flow cytometry. A significant increase in CD21low, IgM memory B cells, Breg and CD8Treg, and a significant decreased in germinal center B cells, and CXCR3+ naïve and memory B cells were observed in SIGMD. These alterations in subsets of B cells, and Breg and CD8Treg cells may play a role in the pathogenesis of SIGMD. PMID:27168952

  14. GITR subverts Foxp3+ Tregs to boost Th9 immunity through regulation of histone acetylation

    PubMed Central

    Xiao, Xiang; Shi, Xiaomin; Fan, Yihui; Zhang, Xiaolong; Wu, Minhao; Lan, Peixiang; Minze, Laurie; Fu, Yang-Xin; Ghobrial, Rafik M.; Liu, Wentao; Li, Xian Chang

    2015-01-01

    Glucocorticoid-induced TNFR-related protein (GITR) is a costimulatory molecule with diverse effects on effector T cells and regulatory T cells (Tregs), but the underlying mechanism remains poorly defined. Here we demonstrate that GITR ligation subverts the induction of Foxp3+ Tregs and directs the activated CD4+ T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumour immunity in vivo. Mechanistically, GITR upregulates the NF-κB family member p50, which recruits histone deacetylases to the Foxp3 locus to produce a ‘closed' chromatin structure. Furthermore, GITR ligation also activates STAT6, and STAT6 renders Il9 locus accessible via recruitment of histone acetyltransferase p300, and together with inhibition of Foxp3, GITR induces strong Th9 responses. Thus, Th9 cells and iTregs are developmentally linked and GITR can subvert tolerogenic conditions to boost Th9 immunity. PMID:26365427

  15. IL-34 is a Treg-specific cytokine and mediates transplant tolerance

    PubMed Central

    Bézie, Séverine; Picarda, Elodie; Ossart, Jason; Tesson, Laurent; Usal, Claire; Renaudin, Karine; Anegon, Ignacio; Guillonneau, Carole

    2015-01-01

    Cytokines and metabolic pathway–controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non–IL-34–expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg–specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance. PMID:26389674

  16. Low-dose IL-2 selectively activates subsets of CD4+ Tregs and NK cells

    PubMed Central

    Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye; Koreth, John; Kim, Haesook T.; Paul, Nicole E.; Murase, Kazuyuki; Whangbo, Jennifer; Alho, Ana C.; Nikiforow, Sarah; Cutler, Corey; Ho, Vincent T.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.; Blazar, Bruce R.; Lacerda, Joao F.; Soiffer, Robert J.

    2016-01-01

    CD4+ regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood. Using mass cytometry, we demonstrate that low concentrations of IL-2 selectively induce STAT5 phosphorylation in Helios+ CD4Tregs and CD56brightCD16– NK cells in vitro. Preferential activation and expansion of Helios+ CD4Tregs and CD56brightCD16– NK cells was also demonstrated in patients with chronic GVHD receiving low-dose IL-2. With prolonged IL-2 treatment for 48 weeks, phenotypic changes were also observed in Helios– CD4Tregs. The effects of low-dose IL-2 therapy on conventional CD4+ T cells and CD8+ T cells were limited to increased expression of PD-1 on effector memory T cells. These studies reveal the selective effects of low-dose IL-2 therapy on Helios+ CD4Tregs and CD56bright NK cells that constitutively express high-affinity IL-2 receptors as well as the indirect effects of prolonged exposure to low concentrations of IL-2 in vivo. PMID:27812545

  17. The roles of serum CXCL16 in circulating Tregs and gastrointestinal stromal tumor cells

    PubMed Central

    Xing, Ya-Nan; Zhang, Jun-Yan; Xu, Hui-Mian

    2016-01-01

    Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the digestive system. Abnormal expression of CXCL16 and its sole receptor, CXCR6, has been demonstrated in many cancers. However, no studies have shown the relationship between CXCL16 or CXCR6 expression and GIST. In this study, we detected CXCL16 and CXCR6 expression in GIST patient samples by using immunohistochemistry analysis and Western blot analysis. Serum CXCL16 level was determined by using enzyme-linked immunosorbent assay. Circulating Tregs were isolated by using flow cytometry. MTT assay, cell cycle assay, and transwell assay were used to test the effects of recombinant CXCL16 on Tregs and GIST cells in vitro. The levels of CXCL16 and CXCR6 protein were higher in cancer tissues than in normal tissues. Serum CXCL16 level and circulating Tregs were higher in GIST patients than that in the healthy volunteers. CXCL16, CXCR6, serum CXCL16, and circulating Tregs were significantly associated with a decreased survival time of patients. Relative to control cells, high concentration recombinant CXCL16 treated Tregs and GIST cells exhibited lower proliferation and mobility rates as assessed by MTT assay and transwell assay, respectively. Taken together, CXCL16 was observed to mediate the inhibitory effects in Tregs and GIST cells, and these involved suppression of the MEK/ERK signaling pathway. PMID:27418838

  18. Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets.

    PubMed

    Montane, Joel; Bischoff, Loraine; Soukhatcheva, Galina; Dai, Derek L; Hardenberg, Gijs; Levings, Megan K; Orban, Paul C; Kieffer, Timothy J; Tan, Rusung; Verchere, C Bruce

    2011-08-01

    Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the CD4+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells and CD8+ IFN-γ–producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes. PMID:21737880

  19. Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg function

    PubMed Central

    Xiao, Yan; Li, Bin; Zhou, Zhaocai; Hancock, Wayne W.; Zhang, Hongtao; Greene, Mark I.

    2010-01-01

    Regulatory T cells (Tregs) are required for the maintenance of immune homeostasis as first clearly described by Herman Waldmann’s laboratory. Dysfunction of Treg cells also leads to fatal autoimmunity in humans and mice. Conversely, the activation of different classes of Tregs operative systemically and within the cancer microenvironment can suppress host anti-tumor immune responses and promote tumor progression. Therefore, the development of new therapeutic approaches to regulate the activity of Treg cells may have considerable clinical potential. FOXP3 is the key transcriptional regulator of Treg development and function. The activity of FOXP3 is regulated by acetylation, a process catalyzed by distinct types of histone/protein acetyltransferases (HATs) that regulate the functions of many transcription factors, independently of FOXP3, as well as non-histone proteins, in addition to their effects on chromatin accessibility. Interactions between FOXP3 and these enzymes determine the suppressive function of FOXP3. Clearly, small molecules targeting these enzymes are candidates for the regulation of Treg function in vaccines and tumor therapies. PMID:20869864

  20. Tregs control the development of symptomatic West Nile virus infection in humans and mice.

    PubMed

    Lanteri, Marion C; O'Brien, Katie M; Purtha, Whitney E; Cameron, Mark J; Lund, Jennifer M; Owen, Rachel E; Heitman, John W; Custer, Brian; Hirschkorn, Dale F; Tobler, Leslie H; Kiely, Nancy; Prince, Harry E; Ndhlovu, Lishomwa C; Nixon, Douglas F; Kamel, Hany T; Kelvin, David J; Busch, Michael P; Rudensky, Alexander Y; Diamond, Michael S; Norris, Philip J

    2009-11-01

    West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection. Here, we show that in 32 blood donors with acute WNV infection, Tregs expanded significantly in the 3 months after index (RNA+) donations in all subjects. Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year after index donation yet did not show differences in systemic T cell or generalized inflammatory responses. In parallel prospective experimental studies, symptomatic WNV-infected mice also developed lower Treg frequencies compared with asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice developed lethal WNV infection at a higher rate than controls. Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans.

  1. Expanded Non-human Primate Tregs Exhibit A Unique Gene Expression Signature and Potently Downregulate Allo-immune Responses

    PubMed Central

    Anderson, Alan; Martens, Christine; Hendrix, Rose; Stempora, Linda; Miller, Wes; Hamby, Kelly; Russell, Maria; Strobert, Elizabeth; Blazar, Bruce R.; Pearson, Thomas C.; Larsen, Christian P.; Kean, Leslie S.

    2009-01-01

    We have established two complementary strategies for purifying naturally occurring regulatory T cells (Tregs) from rhesus macaques in quantities which would be sufficient for use as an in vivo cellular therapeutic. The first identified Tregs based on their being CD4+/CD25bright. The second incorporated CD127, and purified Tregs based on their expression of CD4 and CD25 and their low expression of CD127. Using these purification strategies, we were able to purify as many as 1×106 Tregs from 120cc of peripheral blood. Culture of these cells with anti-CD3, anti-CD28 and IL-2 over 21 days yielded as much as 450-fold expansion, ultimately producing as many as 4.7×108 Tregs. Expanded Treg cultures potently inhibited alloimmune proliferation as measured by a CFSE-MLR assay even at a 1:100 ratio with responder T cells. Furthermore, both responder-specific and third-party Tregs downregulated alloproliferation similarly. Both freshly isolated and cultured Tregs had gene expression signatures distinguishable from concurrently isolated bulk CD4+ T cell populations, as measured by single-plex RT-PCR and gene array. Moreover, an overlapping yet distinct gene expression signature seen in freshly isolated compared to expanded Tregs identifies a subset of Treg genes likely to be functionally significant. PMID:18801023

  2. Absolute Identification by Relative Judgment

    ERIC Educational Resources Information Center

    Stewart, Neil; Brown, Gordon D. A.; Chater, Nick

    2005-01-01

    In unidimensional absolute identification tasks, participants identify stimuli that vary along a single dimension. Performance is surprisingly poor compared with discrimination of the same stimuli. Existing models assume that identification is achieved using long-term representations of absolute magnitudes. The authors propose an alternative…

  3. Be Resolute about Absolute Value

    ERIC Educational Resources Information Center

    Kidd, Margaret L.

    2007-01-01

    This article explores how conceptualization of absolute value can start long before it is introduced. The manner in which absolute value is introduced to students in middle school has far-reaching consequences for their future mathematical understanding. It begins to lay the foundation for students' understanding of algebra, which can change…

  4. RA8, A human anti-CD25 antibody against human treg cells

    SciTech Connect

    Arias, Robyn; Flanagan, Meg; Miller, Keith D.; Nien, Yu-Chih; Hu, Peisheng; Gray, Dixon; Khawli, Leslie A.; Epstein, Alan L.

    2007-06-01

    Although anti-CD25 antibodies exist for clinical use in patients, there is a need for the development of a human Treg antibody that will abrogate the immunosuppressive function of this small but critical T cell subtype. Based upon mounting evidence that the level of Treg cells in the tumor microenvironment correlates with clinical prognosis and stage in man, it appears that Treg cells play an important role in the tumor's ability to overcome host immune responses. In mice, the rat anti-mouse CD25 antibody PC61 causes depletion of CD25-bearing Treg cells both peripherally in lymphatic tissues and in the tumor microenvironment, without inducing symptoms of autoimmunity. A similar antibody, though with the ability to delete Treg cells specifically, would be an important new tool for reversing tumor escape associated with Treg immunosuppression in man. To begin to generate such a reagent, we now describe the development of a human anti-CD25 antibody using a novel yeast display library. The target antigen CD25-Fc was constructed and used for five rounds of selection using a non-immune yeast display library that contained as many as 109 single chain variable fragments (scFv). Two unique clones with low KD values (RA4 and RA8) were then selected to construct fully human anti-CD25 antibodies (IgG1/kappa) for stable expression. One antibody, RA8, showed excellent binding to human CD25+ cell lines and to human Treg cells and appears to be an excellent candidate for the generation of a human reagent that may be used in man for the immunotherapy of cancer.

  5. Absolute calibration of ultraviolet filter photometry

    NASA Technical Reports Server (NTRS)

    Bless, R. C.; Fairchild, T.; Code, A. D.

    1972-01-01

    The essential features of the calibration procedure can be divided into three parts. First, the shape of the bandpass of each photometer was determined by measuring the transmissions of the individual optical components and also by measuring the response of the photometer as a whole. Secondly, each photometer was placed in the essentially-collimated synchrotron radiation bundle maintained at a constant intensity level, and the output signal was determined from about 100 points on the objective. Finally, two or three points on the objective were illuminated by synchrotron radiation at several different intensity levels covering the dynamic range of the photometers. The output signals were placed on an absolute basis by the electron counting technique described earlier.

  6. Heat Shock Protein 60 in Eggs Specifically Induces Tregs and Reduces Liver Immunopathology in Mice with Schistosomiasis Japonica

    PubMed Central

    Zhou, Sha; Jin, Xin; Chen, Xiaojun; Zhu, Jifeng; Xu, Zhipeng; Wang, Xuefeng; Liu, Feng; Hu, Wei; Zhou, Liang; Su, Chuan

    2015-01-01

    Background Parasitic helminths need to suppress the host immune system to establish chronic infections. Paradoxically, immunosuppression induced by the worm also benefits the host by limiting excessive inflammation and tissue damage, which remains the major cause leading to serious morbidity and mortality. Regulatory T cells (Tregs) are key immune regulators of this mutualism. The successive rise in Tregs during schistosome infection plays a critical role in immunoregulation. We and others previously showed that Schistosoma japonicum (S. japonicum) egg antigens (SEA) induce Tregs both in vitro and in vivo. In addition, we identified that SjHSP60 derived from SEA significantly induces Tregs in vivo and in vitro. However, the contribution of SjHSP60 in SEA to Treg induction and the related mechanisms of the Treg induction have not yet been identified. Methodology/Principal Findings In this study, we showed that S. japonicum stress protein HSP60 (SjHSP60) was constitutively and extensively expressed in eggs of S. japonicum. SjHSP60 specially induced Tregs in vivo and in vitro without inducing other CD4+ T sub-populations including Th1, Th2 and Th17 cells. Furthermore, we showed that the SjHSP60-depleted SEA almost lost the ability in vitro and displayed a significant impaired ability to induce Tregs in vivo. Finally, our study illustrated that the mechanisms of SjHSP60-mediated induction of Tregs are through both conversion of CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs and expansion of preexisting CD4+CD25+Foxp3+ Tregs in a TLR4-dependent manner. Conclusions/Significance Collectively, our findings identify SjHSP60 as a major parasitic contributor of Treg induction in S. japonicum egg antigens, which not only contributes to the better understanding of the mechanism of immunoregulation during helminth infection, but also suggests its potential as a therapeutic target for control of immunopathology, allergic and autoimmune diseases. PMID:26418003

  7. The Big Pumpkin Count.

    ERIC Educational Resources Information Center

    Coplestone-Loomis, Lenny

    1981-01-01

    Pumpkin seeds are counted after students convert pumpkins to jack-o-lanterns. Among the activities involved, pupils learn to count by 10s, make estimates, and to construct a visual representation of 1,000. (MP)

  8. miR-146b antagomir-treated human Tregs acquire increased GVHD inhibitory potency.

    PubMed

    Lu, Yunjie; Hippen, Keli L; Lemire, Amanda L; Gu, Jian; Wang, Weizhi; Ni, Xuhao; Ranganathan, Parvathi; Levine, Bruce L; Riley, James L; June, Carl H; Turka, Laurence A; Munn, David H; Garzon, Ramiro; Lu, Ling; Blazar, Bruce R

    2016-09-01

    CD4(+)CD25(+)FoxP3(+) thymic-derived regulatory T cells (tTregs) are indispensable for maintaining immune system equilibrium. Adoptive transfer of tTregs is an effective means of suppressing graft-versus-host disease (GVHD) in murine models and in early human clinical trials. Tumor necrosis factor receptor-associated factor 6 (TRAF6), an ubiquitin-conjugating enzyme that mediates nuclear factor κB (NF-κB) activation, plays an essential role in modulating regulatory T cell survival and function. MicroRNAs (miRNAs) are noncoding RNAs, which mediate RNA silencing and posttranscriptional gene repression. By performing comprehensive TaqMan Low Density Array miRNA assays, we identified 10 miRNAs differentially regulated in human tTreg compared with control T cells. One candidate, miR-146b, is preferentially and highly expressed in human naive tTregs compared with naive CD4 T cells. miRNA prediction software revealed that TRAF6 was the one of the top 10 scored mRNAs involved tTreg function with the highest probability as a potential miR-146b target. Antagomir-mediated knockdown of miRNA-146b, but not another miRNA-146 family member (miRNA-146a), enhanced TRAF6 expression. TRAF6, in turn, increases NF-κB activation, which is essential for tTreg function as well as Foxp3 protein and antiapoptotic gene expression, and downregulates proapoptotic gene expression. miR-146b knockdown increased the nuclear localization and expression of genes regulated by NF-κB, which was associated with enhanced tTreg survival, proliferation, and suppressive function measured in vitro and in vivo. TRAF6 inhibition had the opposite effects. We conclude that an miR-146b-TRAF6-NF-κB-FoxP3 signaling pathway restrains regulatory T cell survival, proliferation, and suppressor function. In vitro exposure of human tTregs to miR-146b antagomirs can be exploited to improve the clinical efficacy of human adoptive tTreg transfer in a GVHD setting. PMID:27485827

  9. Singular perturbation of absolute stability.

    NASA Technical Reports Server (NTRS)

    Siljak, D. D.

    1972-01-01

    It was previously shown (author, 1969) that the regions of absolute stability in the parameter space can be determined when the parameters appear on the right-hand side of the system equations, i.e., the regular case. Here, the effect on absolute stability of a small parameter attached to higher derivatives in the equations (the singular case) is studied. The Lur'e-Postnikov class of nonlinear systems is considered.

  10. Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans

    PubMed Central

    Luo, Tao; Ji, Wen-jie; Yuan, Fei; Guo, Zhao-zeng; Li, Yun-xiao; Dong, Yan; Ma, Yong-qiang; Zhou, Xin; Li, Yu-ming

    2016-01-01

    The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2* signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk. PMID:27353721

  11. IL-10 regulate decidual Tregs apoptosis contributing to the abnormal pregnancy with Toxoplasma gondii infection.

    PubMed

    Lao, Kaixue; Zhao, Mingdong; Li, Zhidan; Liu, Xianbing; Zhang, Haixia; Jiang, Yuzhu; Wang, Yanlin; Hu, Xuemei

    2015-12-01

    This study aims to investigate whether IL-10 regulate decidual Treg cells apoptosis to reverse the abnormal pregnancy outcomes with Toxoplasma gondii (T. gondii) infection. Recombinant mouse IL-10 (rIL-10) treatment and IL-10 deficiency (IL-10(-/-)) abnormal pregnancy animal models with T. gondii infection were established. Apoptosis related molecules cleaved Caspase-3 and Caspase-8 in decidual Treg cells were examined using flow cytometry. The levels of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were up-regulated with T. gondii infection. Compared to infected group, the expressions of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were down-regulated in rIL-10-treated group, while up-regulated in infected IL-10(-/-) group. In addition, pregnant outcomes were improved in rIL-10-treated group, while worse in IL-10(-/-) group compared to infected group. These findings revealed that IL-10 reduced the decidual Treg cells apoptosis contributing to improving adverse pregnant outcomes following T. gondii infection.

  12. New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression.

    PubMed

    Valverde-Villegas, Jacqueline María; Matte, Maria Cristina Cotta; de Medeiros, Rúbia Marília; Chies, José Artur Bogo

    2015-01-01

    Treg and Th17 cell subsets are characterized by the expression of specific transcriptional factors and chemokine receptor as well as by secretion of specific cytokine and chemokines. These subsets are important to the differentiation, expansion, homing capacity, and recruitment of several different immune cell populations to the site of infection. Whereas Treg cells maintain self-tolerance and control the activation and expansion of autoreactive CD4(+) T effector cells through an anti-inflammatory response, Th17 cells, in an exacerbated unregulated proinflammatory response, can promote autoimmunity. Despite such apparently opposite functions, Th17 and Treg cells share common characteristics, and their differentiation pathways are interconnected. Recent studies have revealed quite intricate relations between Treg and Th17 cells in HIV infection and progression to AIDS. Considering Treg cells, different subsets were already investigated in the context of HIV infection, indicating a fluctuation in the total number and frequency throughout the disease course. This review focuses on the recent findings regarding the role of regulatory T and Th17 cells in the context of HIV infection, highlighting the importance of the balance between these two subsets on disease progression.

  13. Cyclic AMP Represents a Crucial Component of Treg Cell-Mediated Immune Regulation

    PubMed Central

    Klein, Matthias; Bopp, Tobias

    2016-01-01

    T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, two different scenarios of cAMP-mediated suppression. In one scenario, Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication directly to the effector T cells (Teff) leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine, which trigger the adenylate cyclases in Teff cells via A2A and A2B receptors, thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation. PMID:27621729

  14. Cyclic AMP Represents a Crucial Component of Treg Cell-Mediated Immune Regulation.

    PubMed

    Klein, Matthias; Bopp, Tobias

    2016-01-01

    T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, two different scenarios of cAMP-mediated suppression. In one scenario, Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication directly to the effector T cells (Teff) leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine, which trigger the adenylate cyclases in Teff cells via A2A and A2B receptors, thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation.

  15. Cyclic AMP Represents a Crucial Component of Treg Cell-Mediated Immune Regulation

    PubMed Central

    Klein, Matthias; Bopp, Tobias

    2016-01-01

    T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, two different scenarios of cAMP-mediated suppression. In one scenario, Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication directly to the effector T cells (Teff) leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine, which trigger the adenylate cyclases in Teff cells via A2A and A2B receptors, thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation.

  16. Altered expression and editing of miRNA-100 regulates iTreg differentiation

    PubMed Central

    Negi, Vinny; Paul, Deepanjan; Das, Sudipta; Bajpai, Prashant; Singh, Suchita; Mukhopadhyay, Arijit; Agrawal, Anurag; Ghosh, Balaram

    2015-01-01

    RNA editing of miRNAs, especially in the seed region, adds another layer to miRNA mediated gene regulation which can modify its targets, altering cellular signaling involved in important processes such as differentiation. In this study, we have explored the role of miRNA editing in CD4+ T cell differentiation. CD4+ T cells are an integral component of the adaptive immune system. Naïve CD4+ T cells, on encountering an antigen, get differentiated either into inflammatory subtypes like Th1, Th2 or Th17, or into immunosuppressive subtype Treg, depending on the cytokine milieu. We found C-to-U editing at fifth position of mature miR-100, specifically in Treg. The C-to-U editing of miR-100 is functionally associated with at least one biologically relevant target change, from MTOR to SMAD2. Treg cell polarization by TGFβ1 was reduced by both edited and unedited miR-100 mimics, but percentage of Treg in PBMCs was only reduced by edited miR-100 mimics, suggesting a model in which de-repression of MTOR due to loss of unedited mir-100, promotes tolerogenic signaling, while gain of edited miR-100 represses SMAD2, thereby limiting the Treg. Such delicately counterbalanced systems are a hallmark of immune plasticity and we propose that miR-100 editing is a novel mechanism toward this end. PMID:26209130

  17. Adenoviral transduction of naive CD4 T cells to study Treg differentiation.

    PubMed

    Warth, Sebastian C; Heissmeyer, Vigo

    2013-08-13

    Regulatory T cells (Tregs) are essential to provide immune tolerance to self as well as to certain foreign antigens. Tregs can be generated from naive CD4 T cells in vitro with TCR- and co-stimulation in the presence of TGFβ and IL-2. This bears enormous potential for future therapies, however, the molecules and signaling pathways that control differentiation are largely unknown. Primary T cells can be manipulated through ectopic gene expression, but common methods fail to target the most important naive state of the T cell prior to primary antigen recognition. Here, we provide a protocol to express ectopic genes in naive CD4 T cells in vitro before inducing Treg differentiation. It applies transduction with the replication-deficient adenovirus and explains its generation and production. The adenovirus can take up large inserts (up to 7 kb) and can be equipped with promoters to achieve high and transient overexpression in T cells. It effectively transduces naive mouse T cells if they express a transgenic Coxsackie adenovirus receptor (CAR). Importantly, after infection the T cells remain naive (CD44(low), CD62L(high)) and resting (CD25(-), CD69(-)) and can be activated and differentiated into Tregs similar to non-infected cells. Thus, this method enables manipulation of CD4 T cell differentiation from its very beginning. It ensures that ectopic gene expression is already in place when early signaling events of the initial TCR stimulation induces cellular changes that eventually lead into Treg differentiation.

  18. Cyclic AMP Represents a Crucial Component of Treg Cell-Mediated Immune Regulation.

    PubMed

    Klein, Matthias; Bopp, Tobias

    2016-01-01

    T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, two different scenarios of cAMP-mediated suppression. In one scenario, Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication directly to the effector T cells (Teff) leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine, which trigger the adenylate cyclases in Teff cells via A2A and A2B receptors, thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation. PMID:27621729

  19. The Absolute Radiometric Calibration of Space - Sensors.

    NASA Astrophysics Data System (ADS)

    Holm, Ronald Gene

    1987-09-01

    The need for absolute radiometric calibration of space-based sensors will continue to increase as new generations of space sensors are developed. A reflectance -based in-flight calibration procedure is used to determine the radiance reaching the entrance pupil of the sensor. This procedure uses ground-based measurements coupled with a radiative transfer code to characterize the effects the atmosphere has on the signal reaching the sensor. The computed radiance is compared to the digital count output of the sensor associated with the image of a test site. This provides an update to the preflight calibration of the system and a check on the on-board internal calibrator. This calibration procedure was used to perform a series of five calibrations of the Landsat-5 Thematic Mapper (TM). For the 12 measurements made in TM bands 1-3, the RMS variation from the mean as a percentage of the mean is (+OR-) 1.9%, and for measurements in the IR, TM bands 4,5, and 7, the value is (+OR-) 3.4%. The RMS variation for all 23 measurements is (+OR-) 2.8%. The absolute calibration techniques were put to another test with a series of three calibration of the SPOT-1 High Resolution Visible, (HRV), sensors. The ratio, HRV-2/HRV-1, of absolute calibration coefficients compared very well with ratios of histogrammed data obtained when the cameras simultaneously imaged the same ground site. Bands PA, B1 and B3 agreed to within 3%, while band B2 showed a 7% difference. The procedure for performing a satellite calibration was then used to demonstrate how a calibrated satellite sensor can be used to quantitatively evaluate surface reflectance over a wide range of surface features. Predicted reflectance factors were compared to values obtained from aircraft -based radiometer data. This procedure was applied on four dates with two different surface conditions per date. A strong correlation, R('2) = .996, was shown between reflectance values determined from satellite imagery and low-flying aircraft

  20. TLR4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation.

    PubMed

    Cao, Anthony T; Yao, Suxia; Stefka, Andrew T; Liu, Zhanju; Qin, Hongwei; Liu, Houpu; Evans-Marin, Heather L; Elson, Charles O; Nagler, Cathryn R; Cong, Yingzi

    2014-11-01

    Tregs play a crucial role in the maintenance of intestinal immune homeostasis. However, significant numbers of Foxp3(+) Tregs accumulate in the inflamed lesions in experimental colitis and in IBD patients. Treg production of the proinflammatory cytokines IFN-γ and/or IL-17 may arguably explain their ineffectiveness in suppressing intestinal inflammation. However, it remains unknown whether iTreg and tTreg produce proinflammatory cytokines and how TLR signaling regulates this process. Here, we found that Foxp3(+)Tregs were increased in the intestines of B6.TLR4(-/-) and B6.IL-10(-/-) mice when compared with WT B6 mice. TLR4(-/-) and IL-10(-/-) resulted in more Tregs within inflamed intestines. The majority of Foxp3(+) Tregs in the spleen was Helios(+)Nrp1(+), whereas most Foxp3(+) Tregs in the intestinal LP were Helios(-)Nrp1(-). More Helios(+)Nrp1(+) Tregs expressed IFN-γ and/or IL-17 than did Helios(-)Nrp1(-) Tregs in the spleen and intestine, which was increased with TLR4(-/-). TLR4 signaling in T cells and APCs inhibited Foxp3(+) induction via MyD88-dependent, TRIF-independent pathways, which was negatively regulated by SOCS3. Collectively, these data demonstrate Helios(+)Nrp1(+) tTregs and Helios(-)Nrp1(-) iTregs produce proinflammatory cytokines in the intestines during inflammation, which was regulated by TLR4 signaling.

  1. Differential Responses of Human Regulatory T Cells (Treg) and Effector T Cells to Rapamycin

    PubMed Central

    Strauss, Laura; Czystowska, Malgorzata; Szajnik, Marta; Mandapathil, Magis; Whiteside, Theresa L.

    2009-01-01

    Background The immunosuppressive drug rapamycin (RAPA) promotes the expansion of CD4+ CD25highFoxp3+ regulatory T cells via mechanisms that remain unknown. Here, we studied expansion, IL-2R-γ chain signaling, survival pathways and resistance to apoptosis in human Treg responding to RAPA. Methodology/Principal Findings CD4+CD25+ and CD4+CD25neg T cells were isolated from PBMC of normal controls (n = 21) using AutoMACS. These T cell subsets were cultured in the presence of anti-CD3/CD28 antibodies and 1000 IU/mL IL-2 for 3 to 6 weeks. RAPA (1–100 nM) was added to half of the cultures. After harvest, the cell phenotype, signaling via the PI3K/mTOR and STAT pathways, expression of survival proteins and Annexin V binding were determined and compared to values obtained with freshly-separated CD4+CD25high and CD4+CD25neg T cells. Suppressor function was tested in co-cultures with autologous CFSE-labeled CD4+CD25neg or CD8+CD25neg T-cell responders. The frequency and suppressor activity of Treg were increased after culture of CD4+CD25+ T cells in the presence of 1–100 nM RAPA (p<0.001). RAPA-expanded Treg were largely CD4+CD25highFoxp3+ cells and were resistant to apoptosis, while CD4+CD25neg T cells were sensitive. Only Treg upregulated anti-apoptotic and down-regulated pro-apoptotic proteins. Treg expressed higher levels of the PTEN protein than CD4+CD25neg cells. Activated Treg±RAPA preferentially phosphorylated STAT5 and STAT3 and did not utilize the PI3K/mTOR pathway. Conclusions/Significance RAPA favors Treg expansion and survival by differentially regulating signaling, proliferation and sensitivity to apoptosis of human effector T cells and Treg after TCR/IL-2 activation. PMID:19543393

  2. Absolute flux scale for radioastronomy

    SciTech Connect

    Ivanov, V.P.; Stankevich, K.S.

    1986-07-01

    The authors propose and provide support for a new absolute flux scale for radio astronomy, which is not encumbered with the inadequacies of the previous scales. In constructing it the method of relative spectra was used (a powerful tool for choosing reference spectra). A review is given of previous flux scales. The authors compare the AIS scale with the scale they propose. Both scales are based on absolute measurements by the ''artificial moon'' method, and they are practically coincident in the range from 0.96 to 6 GHz. At frequencies above 6 GHz, 0.96 GHz, the AIS scale is overestimated because of incorrect extrapolation of the spectra of the primary and secondary standards. The major results which have emerged from this review of absolute scales in radio astronomy are summarized.

  3. Scutellaria flavonoids inhibit tumor-mediated induction of Treg cells via inhibition of TGF-ß1 activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has become evident that tumor-induced Treg cell activity is mostly responsible for the sub-optimal response to therapeutic vaccines. Development of neo-adjuvant strategies targeting TGF-ß and Treg cell activity is therefore imperative. Scutellaria extracts or constituent flavonoids have shown e...

  4. Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated with a reduction in Tim-3 expression.

    PubMed

    Li, Shufeng; Wan, Jinliang; Anderson, William; Sun, Huaqiang; Zhang, Hu; Peng, Xianbo; Yu, Zhaolong; Wang, Teng; Yan, Xinfeng; Smith, Wendy

    2016-04-01

    Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.

  5. Functional Mechanisms of Treg in the Context of HIV Infection and the Janus Face of Immune Suppression

    PubMed Central

    López-Abente, Jacobo; Correa-Rocha, Rafael; Pion, Marjorie

    2016-01-01

    Regulatory T cells (Tregs) play an important role in infections, by modulating host immune responses and avoiding the overreactive immunity that in the case of human immunodeficiency virus (HIV) infection leads to a marked erosion and deregulation of the entire immune system. Therefore, the suppressive function of Treg in HIV-infected patients is critical because of their implication on preventing the immune hyperactivation, even though it could also have a detrimental effect by suppressing HIV-specific immune responses. In recent years, several studies have shown that HIV-1 can directly infect Treg, disturbing their phenotype and suppressive capacity via different mechanisms. These effects include Foxp3 and CD25 downregulation, and the impairment of suppressive capacity. This review describes the functional mechanisms of Treg to modulate immune activation during HIV infection, and how such control is no longer fine-tune orchestrated once Treg itself get infected. We will review the current knowledge about the HIV effects on the Treg cytokine expression, on pathways implying the participation of different ectoenzymes (i.e., CD39/CD73 axis), transcription factors (ICER), and lastly on cyclic adenosine monophosphate (cAMP), one of the keystones in Treg-suppressive function. To define which are the HIV effects upon these regulatory mechanisms is crucial not only for the comprehension of immune deregulation in HIV-infected patients but also for the correct understanding of the role of Tregs in HIV infection. PMID:27242797

  6. Methionine enkephalin (MENK) inhibits tumor growth through regulating CD4+Foxp3+ regulatory T cells (Tregs) in mice.

    PubMed

    Li, Xuan; Meng, Yiming; Plotnikoff, Nicolas P; Youkilis, Gene; Griffin, Noreen; Wang, Enhua; Lu, Changlong; Shan, Fengping

    2015-01-01

    Methionine enkephalin (MENK), an endogenous neuropeptide, plays an crucial role in both neuroendocrine and immune systems. CD4+Foxp3+ regulatory T cells (Tregs) are identified as a major subpopulation of T lymphocytes in suppressing immune system to keep balanced immunity. The aim of this research work was to elucidate the mechanisms via which MENK interacts with Tregs in cancer situation. The influence of MENK on transforming growth factor-β (TGF-β) mediated conversion from naïve CD4+CD25- T cells to CD4+CD25+ Tregs was determined and the data from flow cytometry (FCM) analysis indicated that MENK effectively inhibited the expression of Foxp3 during the process of TGF-βinduction. Furthermore, this inhibiting process was accompanied by diminishing phosphorylation and nuclear translocation of Smad2/3, confirmed by western blot (WB) analysis and immunofluorescence (IF) at molecular level. We established sarcoma mice model with S180 to investigate whether MENK could modulate Tregs in tumor circumstance. Our findings showed that MENK delayed the development of tumor in S180 tumor bearing mice and down-regulated level of Tregs. Together, these novel findings reached a conclusion that MENK could inhibit Tregs activity directly and retard tumor development through down-regulating Tregs in mice. This work advances the deepening understanding of the influence of MENK on Tregs in cancer situation, and relation of MENK with immune system, supporting the implication of MENK as a new strategy for cancer immunotherapy.

  7. Methionine Enkephalin (MENK) Inhibits tumor growth through regulating CD4+Foxp3+ Regulatory T cells (Tregs) in mice

    PubMed Central

    Li, Xuan; Meng, Yiming; Plotnikoff, Nicolas P; Youkilis, Gene; Griffin, Noreen; Wang, Enhua; Lu, Changlong; Shan, Fengping

    2015-01-01

    Methionine enkephalin (MENK), an endogenous neuropeptide, plays an crucial role in both neuroendocrine and immune systems. CD4+Foxp3+ regulatory T cells (Tregs) are identified as a major subpopulation of T lymphocytes in suppressing immune system to keep balanced immunity. The aim of this research work was to elucidate the mechanisms via which MENK interacts with Tregs in cancer situation. The influence of MENK on transforming growth factor-β (TGF-β) mediated conversion from naïve CD4+CD25- T cells to CD4+CD25+ Tregs was determined and the data from flow cytometry (FCM) analysis indicated that MENK effectively inhibited the expression of Foxp3 during the process of TGF-βinduction. Furthermore, this inhibiting process was accompanied by diminishing phosphorylation and nuclear translocation of Smad2/3, confirmed by western blot (WB) analysis and immunofluorescence (IF) at molecular level. We established sarcoma mice model with S180 to investigate whether MENK could modulate Tregs in tumor circumstance. Our findings showed that MENK delayed the development of tumor in S180 tumor bearing mice and down-regulated level of Tregs. Together, these novel findings reached a conclusion that MENK could inhibit Tregs activity directly and retard tumor development through down-regulating Tregs in mice. This work advances the deepening understanding of the influence of MENK on Tregs in cancer situation, and relation of MENK with immune system, supporting the implication of MENK as a new strategy for cancer immunotherapy. PMID:25701137

  8. Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment.

    PubMed

    Govindaraj, Chindu; Scalzo-Inguanti, Karen; Madondo, Mutsa; Hallo, Julene; Flanagan, Katie; Quinn, Michael; Plebanski, Magdalena

    2013-10-01

    Ovarian cancer is a prevalent gynecological malignancy with potent immune-suppression capabilities; regulatory T cells (Tregs) are significant contributors to this immune-suppression. As ovarian cancer patients present with high levels of TNF and Tregs expressing TNFR2 are associated with maximal suppressive capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+ Tregs from tumor-associated ascites were the most potent suppressor T cell fraction. They were abundantly present within the ascites and more suppressive than peripheral blood TNFR2+ Tregs in patients. The increased suppressive capacity can be explained by a distinct cell surface expression profile, which includes high levels of CD39, CD73, TGF-β and GARP. Additionally, CD73 expression level on TNFR2+ Tregs was inversely correlated with IFN-γ production by effector T cells. This Treg fraction can be selectively recruited into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs may offer new approaches to enhance the poor survival rates of ovarian cancer.

  9. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy

    PubMed Central

    2014-01-01

    Background Several types of T cells have been associated with the pathogenesis of unexplained recurrent spontaneous abortion (URSA), including Th1/Th2/Th17/Tregs cell. It has been appreciated that immunotherapy with paternal or third party lymphocytes is an effective method of treatment for URSA patients. The balance of Th1/Th2 cells could be maintained and an increase of Treg cells would be beneficial after immunotherapy; however, the mechanism by which the Th17/Treg balance affects URSA has not yet been fully elucidated. Methods Here, we used flow cytometry, liquid chip technology and quantitative real-time PCR (qPCR) methods to characterize Th17/Treg cell populations after immunotherapy. We found that after immunotherapy in URSA patients, the percentage of Th17 cells decreased and the percentage of Treg cells in peripheral blood mononuclear cells (PBMC) increased, as detected by flow cytometry. Results Immunotherapy may induce a decrease in the Th17/Treg ratio and the Treg bias, which may be beneficial for the maintenance of pregnancy. The expression level of ROR gamma t, a transcription factor found in Th17 cells, decreased and the expression of the Treg-specific transcription factor Foxp3 increased in peripheral blood as detected by qPCR. Immunotherapy may induce a decrease in the ratio of ROR gamma t to Foxp3 and a Treg cell bias, which would be beneficial for pregnancy maintenance. The secretion of the Treg-associated cytokine TGF-beta, as well as Th2 cytokines, was increased in serum, while the secretion of Th17-associated cytokine IL-17A and Th1 cytokine production was decreased. The Th1/Th2 cytokine ratio significantly decreased. Similarly, the Th17/Treg ratio significantly decreased in the total patient after immunotherapy. Conclusions These results indicate that in patients with URSA, immunotherapy with mononuclear cells derived from the baby’s father could affect both Th1/Th2 and Th17/Treg balance, and we found that the Th2 and Treg bias would be

  10. Citrate Attenuates Adenine-Induced Chronic Renal Failure in Rats by Modulating the Th17/Treg Cell Balance.

    PubMed

    Ou, Yan; Li, Shuiqin; Zhu, Xiaojing; Gui, Baosong; Yao, Ganglian; Ma, Liqun; Zhu, Dan; Fu, Rongguo; Ge, Heng; Wang, Li; Jia, Lining; Tian, Lifang; Duan, Zhaoyang

    2016-02-01

    Citrate is commonly used as an anticoagulant in hemodialysis for chronic renal failure (CRF) and for the regulation of the immune dysfunction in CRF patients. The objective of this study was to investigate the effect of citrate on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in CRF. The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were significantly increased in the CRF model group compared to the control group, and were decreased in the citrate-treated groups. Citrate treatment inhibited the viability of Th17 cells while elevating the viability of Treg cells in CRF rats. Moreover, Th17-related cytokines significantly decreased while the Treg-related cytokines significantly increased with citrate treatment. Moreover, citrate had a negative influence on the deviation of Th17/Treg cells in CRF rats. Therefore, our study suggests that citrate had an anti-inflammatory effect on CRF through the modulation of the Th17/Treg balance.

  11. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin

    PubMed Central

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-01-01

    Abstract Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4+CD25hiCD127−/low cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment. PMID:26844452

  12. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

    PubMed

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-02-01

    Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment.

  13. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

    PubMed

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-02-01

    Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment. PMID:26844452

  14. Relativistic Absolutism in Moral Education.

    ERIC Educational Resources Information Center

    Vogt, W. Paul

    1982-01-01

    Discusses Emile Durkheim's "Moral Education: A Study in the Theory and Application of the Sociology of Education," which holds that morally healthy societies may vary in culture and organization but must possess absolute rules of moral behavior. Compares this moral theory with current theory and practice of American educators. (MJL)

  15. Absolute transition probabilities of phosphorus.

    NASA Technical Reports Server (NTRS)

    Miller, M. H.; Roig, R. A.; Bengtson, R. D.

    1971-01-01

    Use of a gas-driven shock tube to measure the absolute strengths of 21 P I lines and 126 P II lines (from 3300 to 6900 A). Accuracy for prominent, isolated neutral and ionic lines is estimated to be 28 to 40% and 18 to 30%, respectively. The data and the corresponding theoretical predictions are examined for conformity with the sum rules.-

  16. A tax on luxury: HTLV-I infection of CD4+CD25+ Tregs.

    PubMed

    Fujinami, Robert S

    2005-05-01

    Almost a quarter of a century ago, Oldstone and colleagues proposed that infection of cells by noncytopathic viruses may lead to an alteration of the cells' ability to produce certain products or perform certain tasks, i.e., inhibition of "luxury function." In this issue of the JCI, this topic has been revisited by Yamano et al., who demonstrate that human T cell lymphotropic virus type I (HTLV-I) infection of CD4(+)CD25(+) Tregs in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) results in a decrease in FOXP3 mRNA and protein expression. This leads to the inability of HTLV-I-infected CD4(+)CD25(+) Tregs to inhibit the proliferation of CD4(+)CD25(-) Tregs, due to the effect of the HTLV-I tax gene. Defects in the Treg population could be responsible for the large numbers of virus-specific T cells and occurrence of lymphoproliferation and inflammatory autoimmune disease in HAM/TSP patients.

  17. Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

    PubMed Central

    Feng, Ting; Elson, Charles O.; Cong, Yingzi

    2010-01-01

    The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis. PMID:21111079

  18. Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis.

    PubMed

    Huang, Zhuochun; Yang, Bin; Shi, Yunying; Cai, Bei; Li, Yi; Feng, Weihua; Fu, Yang; Luo, Limei; Wang, Lanlan

    2012-09-01

    Anti-TNF-α therapies have been applied in RA treatment, but the regulatory effect of the drug on immune system is not clear. In this study, we included 33 active RA patients and divided them into two groups. One group received anti-TNF-α mAb+methotrexate for 24 weeks, the other group got placebo+methotrexate for the first 12 weeks and anti-TNF-α mAb+methotrexate for another 12 weeks. Circulatory regulatory T cell (Treg) and effector T cell (Teff) frequency was analyzed pre-therapy and week 12 and week 24 for both group patients by flowcytometry. Our results indicated significantly elevated Treg and decreased Teff at week 24 compared with pre-therapy and week 12 for both group patients, and a little higher Treg and lower Teff frequency in anti-TNF-α therapy group than in placebo therapy patients. Our results demonstrated anti-TNF-α therapy has regulatory effect on immune system of RA patients by promoting Treg proportion increase and suppressing Teff.

  19. T regulatory (Treg) and T helper 17 (Th17) lymphocytes in thyroid autoimmunity.

    PubMed

    González-Amaro, Roberto; Marazuela, Mónica

    2016-04-01

    Different immune cell subsets have a relevant role in the pathogenesis of and tissue damage seen in autoimmune thyroid diseases (AITD), including T regulatory (Treg) lymphocytes and T helper (Th) 17 cells. There are several types of CD4+ Treg cells (Foxp3+, CD69+, Tr1), which are able to prevent the appearance of autoimmune diseases, down regulating the immune response and the inflammatory phenomenon. However, despite their presence in peripheral blood and thyroid tissue from patients with AITD, these cells are apparently unable to put down the autoimmune process. Moreover, many reports indicate the involvement of Th17 cells in chronic inflammatory diseases, including AITD. Nevertheless, it is now evident that these lymphocytes show a remarkable plasticity, giving rise to anti-inflammatory (including Treg lymphocytes) and pro-inflammatory cell subtypes. Nowadays, both Treg and Th17 cells must be considered as key elements in the pathogenesis of AITD as well as plausible potential targets for the next generation of therapeutic options of this condition.

  20. Depletion of fat-resident Treg cells prevents age-associated insulin resistance.

    PubMed

    Bapat, Sagar P; Myoung Suh, Jae; Fang, Sungsoon; Liu, Sihao; Zhang, Yang; Cheng, Albert; Zhou, Carmen; Liang, Yuqiong; LeBlanc, Mathias; Liddle, Christopher; Atkins, Annette R; Yu, Ruth T; Downes, Michael; Evans, Ronald M; Zheng, Ye

    2015-12-01

    Age-associated insulin resistance (IR) and obesity-associated IR are two physiologically distinct forms of adult-onset diabetes. While macrophage-driven inflammation is a core driver of obesity-associated IR, the underlying mechanisms of the obesity-independent yet highly prevalent age-associated IR are largely unexplored. Here we show, using comparative adipo-immune profiling in mice, that fat-resident regulatory T cells, termed fTreg cells, accumulate in adipose tissue as a function of age, but not obesity. Supporting the existence of two distinct mechanisms underlying IR, mice deficient in fTreg cells are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. By contrast, selective depletion of fTreg cells via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. These findings establish that distinct immune cell populations within adipose tissue underlie ageing- and obesity-associated IR, and implicate fTreg cells as adipo-immune drivers and potential therapeutic targets in the treatment of age-associated IR.

  1. Selective Sparing of Human Tregs by Pharmacologic Inhibitors of the Phosphatidylinositol 3-Kinase and MEK Pathways

    PubMed Central

    Zwang, N. A.; Zhang, R.; Germana, S.; Fan, M. Y.; Hastings, W. D.; Cao, A.; Turka, L. A.

    2016-01-01

    Phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated (MEK) signaling are central to the survival and proliferation of many cell types. Multiple lines of investigation in murine models have shown that control of the PI3K pathway is particularly important for regulatory T cell (Treg) stability and function. PI3K and MEK inhibitors are being introduced into the clinic, and we hypothesized that pharmacologic inhibition of PI3K, and possibly MEK, in mixed cultures of human mononuclear cells would preferentially affect CD4+ and CD8+ lymphocytes compared with Tregs. We tested this hypothesis using four readouts: proliferation, activation, functional suppression, and signaling. Results showed that Tregs were less susceptible to inhibition by both δ and α isoform–specific PI3K inhibitors and by an MEK inhibitor compared with their conventional CD4+ and CD8+ counterparts. These studies suggest less functional reliance on PI3K and MEK signaling in Tregs compared with conventional CD4+ and CD8+ lymphocytes. Therefore, the PI3K and MEK pathways are attractive pharmacologic targets for transplantation and treatment of autoimmunity. PMID:27017850

  2. In vivo imaging of Tregs providing immune privilege to the hematopoietic stem cell niche

    PubMed Central

    Fujisaki, Joji; Wu, Juwell; Carlson, Alicia L.; Silberstein, Lev; Putheti, Prabhakar; Larocca, Rafael; Gao, Wenda; Saito, Toshiki I.; Celso, Cristina Lo; Tsuyuzaki, Hitoshi; Sato, Tatsuyuki; Côté, Daniel; Sykes, Megan; Strom, Terry B.; Scadden, David T.; Lin, Charles P.

    2013-01-01

    Stem cells reside in a specialized regulatory microenvironment or niche1,2, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity1-3. The niche may also protect stem cells from environmental insults3 including cytotoxic chemotherapy and perhaps pathogenic immunity4. The testis, hair follicle, and placenta are all sites of residence for stem cells and are immune suppressive environments, called immune privileged (IP) sites, where multiple mechanisms conspire to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression (IS)4. We sought to determine if somatic stem cell niches more broadly are IP sites by examining the hematopoietic stem/progenitor cell (HSPC) niche1,2,5-7 in the bone marrow (BM), a site where immune reactivity exists8,9. We observed persistence of allo-HSPCs in non-irradiated recipients for 30 days without IS with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T cells (Tregs). High resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with Tregs that accumulated on the endosteal surface in the calvarial and trabecular BM. Tregs appear to participate in creating a localized zone where HSPCs reside and where Tregs are necessary for allo-HSPC persistence. In addition to processes supporting stem cell function, the niche will provide a relative sanctuary from immune attack. PMID:21654805

  3. Selective Sparing of Human Tregs by Pharmacologic Inhibitors of the Phosphatidylinositol 3-Kinase and MEK Pathways.

    PubMed

    Zwang, N A; Zhang, R; Germana, S; Fan, M Y; Hastings, W D; Cao, A; Turka, L A

    2016-09-01

    Phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated (MEK) signaling are central to the survival and proliferation of many cell types. Multiple lines of investigation in murine models have shown that control of the PI3K pathway is particularly important for regulatory T cell (Treg) stability and function. PI3K and MEK inhibitors are being introduced into the clinic, and we hypothesized that pharmacologic inhibition of PI3K, and possibly MEK, in mixed cultures of human mononuclear cells would preferentially affect CD4(+) and CD8(+) lymphocytes compared with Tregs. We tested this hypothesis using four readouts: proliferation, activation, functional suppression, and signaling. Results showed that Tregs were less susceptible to inhibition by both δ and α isoform-specific PI3K inhibitors and by an MEK inhibitor compared with their conventional CD4(+) and CD8(+) counterparts. These studies suggest less functional reliance on PI3K and MEK signaling in Tregs compared with conventional CD4(+) and CD8(+) lymphocytes. Therefore, the PI3K and MEK pathways are attractive pharmacologic targets for transplantation and treatment of autoimmunity. PMID:27017850

  4. CSF cell count

    MedlinePlus

    The normal white blood cell count is between 0 and 5. The normal red blood cell count is 0. Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about ... use different measurements or may test different specimens.

  5. Counting Sheep in Basque

    ERIC Educational Resources Information Center

    Araujo, Frank P.

    1975-01-01

    Demonstrates the interplay of a cognitive system, the Basque numerative system, and a behavioral one, counting sheep. The significant features of the Basque numerative system are analyzed; then it is shown how use of these features facilitates the counting of sheep on open ranges by Basque sheep farmers in California. (Author/RM)

  6. Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus.

    PubMed

    Handono, Kusworini; Firdausi, Sevita Nuril; Pratama, Mirza Zaka; Endharti, Agustina Tri; Kalim, Handono

    2016-03-01

    The aim of this study was to determine the role of vitamin A in modulating T helper 17 (Th17) and regulatory T cell (Treg) balance in systemic lupus erythematosus (SLE) patients. Sixty-two female SLE patients and sixty-two female controls were measured for vitamin A levels from serum by enzyme-linked immunosorbent assay (ELISA) and percentages of Th17 and Treg from peripheral blood mononuclear cells (PBMC) by flow cytometry. We also performed an in vitro study to evaluate the effects of retinoic acid treatment (0, 0.1, 0.2, and 0.3 μg/ml) in modulating Th17/Treg balance in CD4(+) T cell culture from hypovitaminosis A SLE patients. Th17 and Treg percentages from cell cultures were measured by flow cytometry. Vitamin A levels in the SLE patients were lower compared to those in the healthy control (46.9 ± 43.4 vs. 75.6 ± 73.1 ng/ml, p = 0.015). Vitamin A levels also had a negative correlation to Th17 percentages in the SLE patients (p = 0.000, R = -0.642). Th17 percentages in the hypovitaminosis A SLE patients were higher compared to those SLE patients with normal vitamin A levels (10.9 ± 5.3 vs. 2.9 ± 2.2 %, p = 0.000). Treatment of 0.3 μg/ml of retinoic acid could increase Treg differentiation (33.9 ± 1.6 vs. 21.8 ± 1.1 %, p = 0.000) and decrease Th17 differentiation (27.2 ± 2.5 vs. 37.4 ± 1.3 %, p = 0.000). In conclusion, vitamin A has important roles in modulating Th17/Treg balance in the SLE patients shown by the significant decrease of vitamin A levels in the SLE patients which negatively correlate with Th17 population, and treatment of retinoic acid could decrease Th17 and increase Treg percentages in CD4(+) T cells cultures.

  7. Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner

    PubMed Central

    Watanabe, Nobumasa; Kaminuma, Osamu; Kitamura, Noriko; Hiroi, Takachika

    2016-01-01

    Th17 cells and Foxp3+ regulatory T cells (Tregs) are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their interactions, we describe the results of experiments employing mouse models of intestinal inflammation by transferring antigen-specific Th cells (Th1, Th2, and Th17) differentiated in vitro followed by the administration of the cognate antigen via enema. We show that cotransfer of induced Tregs (iTregs) suppressed Th1- and Th2-mediated colon inflammation. In contrast, colon inflammation induced by transfer of Th17 cells, was augmented by the cotransfer of iTregs. Furthermore, oral delivery of antigen potentiated Th17-mediated colon inflammation. Administration of a blocking antibody against cytotoxic T lymphocyte-associated antigen 4 (CTLA4) abrogated the effects of cotransfer of iTregs, while the injection of a soluble recombinant immunoglobulin (Ig) fusion protein, CTLA4-Ig substituted for the cotransfer of iTregs. These results suggest that antigen-specific activation of iTregs in a local environment stimulates the Th17-mediated inflammatory response in a CTLA4-dependent manner. PMID:26950218

  8. Follicular Lymphoma Tregs Have a Distinct Transcription Profile Impacting Their Migration and Retention in the Malignant Lymph Node

    PubMed Central

    Hyrien, Ollivier; Burack, W. Richard; Quataert, Sally A.; Baker, Christina M.; Azadniv, Mitra; Welle, Stephen L.; Ansell, Stephen M.; Kim, Minsoo; Bernstein, Steven H.

    2016-01-01

    We have previously shown that regulatory T cells (Tregs) infiltrating follicular lymphoma lymph nodes are quantitatively and qualitatively different than those infiltrating normal and reactive nodes. To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of follicular lymphoma nodal tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of the chemokine receptor CXCR5 as well as the secretion of the chemokines CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how follicular lymphoma nodal Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets. PMID:27228053

  9. Optomechanics for absolute rotation detection

    NASA Astrophysics Data System (ADS)

    Davuluri, Sankar

    2016-07-01

    In this article, we present an application of optomechanical cavity for the absolute rotation detection. The optomechanical cavity is arranged in a Michelson interferometer in such a way that the classical centrifugal force due to rotation changes the length of the optomechanical cavity. The change in the cavity length induces a shift in the frequency of the cavity mode. The phase shift corresponding to the frequency shift in the cavity mode is measured at the interferometer output to estimate the angular velocity of absolute rotation. We derived an analytic expression to estimate the minimum detectable rotation rate in our scheme for a given optomechanical cavity. Temperature dependence of the rotation detection sensitivity is studied.

  10. Moral absolutism and ectopic pregnancy.

    PubMed

    Kaczor, C

    2001-02-01

    If one accepts a version of absolutism that excludes the intentional killing of any innocent human person from conception to natural death, ectopic pregnancy poses vexing difficulties. Given that the embryonic life almost certainly will die anyway, how can one retain one's moral principle and yet adequately respond to a situation that gravely threatens the life of the mother and her future fertility? The four options of treatment most often discussed in the literature are non-intervention, salpingectomy (removal of tube with embryo), salpingostomy (removal of embryo alone), and use of methotrexate (MXT). In this essay, I review these four options and introduce a fifth (the milking technique). In order to assess these options in terms of the absolutism mentioned, it will also be necessary to discuss various accounts of the intention/foresight distinction. I conclude that salpingectomy, salpingostomy, and the milking technique are compatible with absolutist presuppositions, but not the use of methotrexate.

  11. Moral absolutism and ectopic pregnancy.

    PubMed

    Kaczor, C

    2001-02-01

    If one accepts a version of absolutism that excludes the intentional killing of any innocent human person from conception to natural death, ectopic pregnancy poses vexing difficulties. Given that the embryonic life almost certainly will die anyway, how can one retain one's moral principle and yet adequately respond to a situation that gravely threatens the life of the mother and her future fertility? The four options of treatment most often discussed in the literature are non-intervention, salpingectomy (removal of tube with embryo), salpingostomy (removal of embryo alone), and use of methotrexate (MXT). In this essay, I review these four options and introduce a fifth (the milking technique). In order to assess these options in terms of the absolutism mentioned, it will also be necessary to discuss various accounts of the intention/foresight distinction. I conclude that salpingectomy, salpingostomy, and the milking technique are compatible with absolutist presuppositions, but not the use of methotrexate. PMID:11262641

  12. The Absolute Spectrum Polarimeter (ASP)

    NASA Technical Reports Server (NTRS)

    Kogut, A. J.

    2010-01-01

    The Absolute Spectrum Polarimeter (ASP) is an Explorer-class mission to map the absolute intensity and linear polarization of the cosmic microwave background and diffuse astrophysical foregrounds over the full sky from 30 GHz to 5 THz. The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r much greater than 1O(raised to the power of { -3}) and Compton distortion y < 10 (raised to the power of{-6}). We describe the ASP instrument and mission architecture needed to detect the signature of an inflationary epoch in the early universe using only 4 semiconductor bolometers.

  13. Classification images predict absolute efficiency.

    PubMed

    Murray, Richard F; Bennett, Patrick J; Sekuler, Allison B

    2005-02-24

    How well do classification images characterize human observers' strategies in perceptual tasks? We show mathematically that from the classification image of a noisy linear observer, it is possible to recover the observer's absolute efficiency. If we could similarly predict human observers' performance from their classification images, this would suggest that the linear model that underlies use of the classification image method is adequate over the small range of stimuli typically encountered in a classification image experiment, and that a classification image captures most important aspects of human observers' performance over this range. In a contrast discrimination task and in a shape discrimination task, we found that observers' absolute efficiencies were generally well predicted by their classification images, although consistently slightly (approximately 13%) higher than predicted. We consider whether a number of plausible nonlinearities can account for the slight under prediction, and of these we find that only a form of phase uncertainty can account for the discrepancy.

  14. Absolute calibration of optical flats

    DOEpatents

    Sommargren, Gary E.

    2005-04-05

    The invention uses the phase shifting diffraction interferometer (PSDI) to provide a true point-by-point measurement of absolute flatness over the surface of optical flats. Beams exiting the fiber optics in a PSDI have perfect spherical wavefronts. The measurement beam is reflected from the optical flat and passed through an auxiliary optic to then be combined with the reference beam on a CCD. The combined beams include phase errors due to both the optic under test and the auxiliary optic. Standard phase extraction algorithms are used to calculate this combined phase error. The optical flat is then removed from the system and the measurement fiber is moved to recombine the two beams. The newly combined beams include only the phase errors due to the auxiliary optic. When the second phase measurement is subtracted from the first phase measurement, the absolute phase error of the optical flat is obtained.

  15. AUTOMATIC COUNTING APPARATUS

    DOEpatents

    Howell, W.D.

    1957-08-20

    An apparatus for automatically recording the results of counting operations on trains of electrical pulses is described. The disadvantages of prior devices utilizing the two common methods of obtaining the count rate are overcome by this apparatus; in the case of time controlled operation, the disclosed system automatically records amy information stored by the scaler but not transferred to the printer at the end of the predetermined time controlled operations and, in the case of count controlled operation, provision is made to prevent a weak sample from occupying the apparatus for an excessively long period of time.

  16. Superiority of rapamycin over tacrolimus in preserving nonhuman primate Treg half-life and phenotype after adoptive transfer.

    PubMed

    Singh, K; Stempora, L; Harvey, R D; Kirk, A D; Larsen, C P; Blazar, B R; Kean, L S

    2014-12-01

    Many critical issues remain concerning how best to deploy adoptive regulatory T cell (Treg) immunotherapy to the clinic. These include a determination of their pharmacokinetic characteristics, their optimal dose, their phenotypic stability and the best therapies with which to pair Tregs. By performing a CFSE-labeled autologous Treg pulse experiment, we determined that the accessible peripheral blood Treg pool in rhesus macaques is quite large (75 ± 11 × 10(6) Tregs/kg). Pharmacokinetic analysis revealed that Tregs have two phases of elimination: an α phase, with a T1/2 in the peripheral blood of 32.4 ± 11.3 h and a β phase with a T1/2 of 120.4 ± 19.7 h. In addition to their short initial half-life, Tregs underwent rapid phenotypic shifts after infusion, with significant loss of both CD25 and FoxP3 by day +6. While tacrolimus stabilized CD25 expression, it did not improve T1/2 , nor mitigate the loss of FoxP3. In contrast, rapamycin significantly stabilized both CD25 and FoxP3, and supported an increased half-life, with an α phase of 67.7 ± 6.9 h and a β phase of 252.1 ± 54.9 h. These results suggest that rapamycin may be a necessary addition to Treg immunotherapy, and that tacrolimus may be deleterious to Treg integrity posttransfer.

  17. Sinomenine induces the generation of intestinal Treg cells and attenuates arthritis via activation of aryl hydrocarbon receptor.

    PubMed

    Tong, Bei; Yuan, Xusheng; Dou, Yannong; Wu, Xin; Wang, Yuhui; Xia, Yufeng; Dai, Yue

    2016-10-01

    Sinomenine (SIN), an anti-arthritis drug, has previously been proven to exert immunomodulatory activity in rats by inducing intestinal regulatory T-cells (Treg cells). Here, we assessed the effect of SIN on the generation and function of Treg cells in autoimmune arthritis, and the underlying mechanisms in view of aryl hydrocarbon receptor (AhR). The proportions of Treg cells and IL-17-producing T-cells (Th17 cells) differentiated from naive T-cells were analyzed by flow cytometric analysis. The AhR agonistic effect of SIN was tested by analyzing the activation of downstream signaling pathways and target genes. The dependence of intestinal Treg cell induction and arthritis alleviation by SIN on AhR activation was confirmed in a mouse collagen-induced arthritis (CIA) model. SIN promoted the differentiation and function of intestinal Treg cells in vitro. It induced the expression and activity of AhR target gene, promoted AhR/Hsp90 dissociation and AhR nuclear translocation, induced XRE reporter activity, and facilitated AhR/XRE binding in vitro, displaying the potential to be an agonist of AhR. In CIA mice, SIN induced the generation of intestinal Treg cells, and facilitated the immunosuppressive function of these Treg cells as shown by an adoptive transfer test. In addition, the induction of intestinal Treg cells and the anti-arthritic effect of SIN in CIA mice could be largely diminished by the AhR antagonist resveratrol. SIN attenuates arthritis by promoting the generation and function of Treg cells in an AhR-dependent manner. PMID:27617398

  18. Blood Count Tests

    MedlinePlus

    ... white blood cells (WBC), and platelets. Blood count tests measure the number and types of cells in ... helps doctors check on your overall health. The tests can also help to diagnose diseases and conditions ...

  19. Counting Knights and Knaves

    ERIC Educational Resources Information Center

    Levin,Oscar; Roberts, Gerri M.

    2013-01-01

    To understand better some of the classic knights and knaves puzzles, we count them. Doing so reveals a surprising connection between puzzles and solutions, and highlights some beautiful combinatorial identities.

  20. Mathematical Model for Absolute Magnetic Measuring Systems in Industrial Applications

    NASA Astrophysics Data System (ADS)

    Fügenschuh, Armin; Fügenschuh, Marzena; Ludszuweit, Marina; Mojsic, Aleksandar; Sokół, Joanna

    2015-09-01

    Scales for measuring systems are either based on incremental or absolute measuring methods. Incremental scales need to initialize a measurement cycle at a reference point. From there, the position is computed by counting increments of a periodic graduation. Absolute methods do not need reference points, since the position can be read directly from the scale. The positions on the complete scales are encoded using two incremental tracks with different graduation. We present a new method for absolute measuring using only one track for position encoding up to micrometre range. Instead of the common perpendicular magnetic areas, we use a pattern of trapezoidal magnetic areas, to store more complex information. For positioning, we use the magnetic field where every position is characterized by a set of values measured by a hall sensor array. We implement a method for reconstruction of absolute positions from the set of unique measured values. We compare two patterns with respect to uniqueness, accuracy, stability and robustness of positioning. We discuss how stability and robustness are influenced by different errors during the measurement in real applications and how those errors can be compensated.

  1. In-flight Absolute Radiometric Calibration of the Thematic Mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, D.; Savage, R. K.

    1984-01-01

    The Thematic Mapper (TM) multispectral scanner system was placed into Earth orbit on July 16, 1982, as part of NASA's LANDSAT 4 payload. To determine temporal changes of the absolute radiometric calibration of the entire system in flight, spectroradiometric measurements of the ground and the atmosphere are made simultaneously with TM image acquisitions over the White Sands, New Mexico area. By entering the measured values into an atmospheric radiative transfer program, the radiance levels at the entrance pupil of the TM in four of the TM spectral bands are determined. These levels are compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors. By reference to an adjacent, larger uniform area, the calibration is extended to all 16 detectors in each of the three bands.

  2. In-flight absolute radiometric calibration of the thematic mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, R. D.; Savage, R. K.

    1984-01-01

    In order to determine temporal changes of the absolute radiometric calibration of the entire TM system in flight spectroradiometric measurements of the ground and the atmosphere were made simultaneously with TM image collections over the White Sands, New Mexico area. By entering the measured values in an atmospheric radiative transfer program, the radiance levels in four of the spectral bands of the TM were determined, band 1:0.45 to 0.52 micrometers, band 2:0.53 to 0.61 micrometers band 3:0.62 to 0.70 micrometers and 4:0.78 to 0.91 micrometers. These levels were compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors.

  3. In-flight absolute radiometric calibration of the Thematic Mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, R. D.; Savage, R. K.

    1984-01-01

    In order to determine temporal changes of the absolute radiometric calibration of the entire TM system in flight spectroradiometric measurements of the ground and the atmosphere were made simultaneously with TM image collections over the White Sands, NM area. By entering the measured values in an atmospheric radiative transfer program, the radiance levels in four of the spectral bands of the TM were determined, band 1: 0.45 to 0.52 micrometers, band 2: 0.53 to 0.61 micrometers, band 3: 0.62 to 0.70 micrometers, and 4: 0.78 to 0.91 micrometers. These levels were compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors. Previously announced in STAR as N84-15633

  4. Recovery of absolute threshold with UVA-induced retinal damage

    SciTech Connect

    Henton, W.W.; Sykes, S.M.

    1984-06-01

    A within-trial psychophysical procedure tracked the initial loss and subsequent recovery of visual thresholds in albino rats exposed to ultraviolet light at 350 nanometers and 0.4 milliwatts per square centimeter. Absolute thresholds increased up to 5 log units immediately following the 15 hour ultraviolet exposure, with a daily recovery of 1-2 log to asymptotic thresholds over a 7-day post-exposure period. The corresponding retinal damage on Day 1 included extensive vesiculation of the photoreceptor outer segments, vacuolation of the inner segments, and pyknosis of cell nuclei. The total number of photoreceptor nuclei and outer segments was unchanged relative to control eyes through post-exposure Day 3. Both nuclei and outer segment counts then consistently decreased 15-20 percent between Days 3-7. The two-stage loss of photoreceptors but daily recovery of absolute thresholds again suggests a significant dissociation of retinal structure and psychophysical function in light-induced ocular pathology.

  5. The AFGL absolute gravity program

    NASA Technical Reports Server (NTRS)

    Hammond, J. A.; Iliff, R. L.

    1978-01-01

    A brief discussion of the AFGL's (Air Force Geophysics Laboratory) program in absolute gravity is presented. Support of outside work and in-house studies relating to gravity instrumentation are discussed. A description of the current transportable system is included and the latest results are presented. These results show good agreement with measurements at the AFGL site by an Italian system. The accuracy obtained by the transportable apparatus is better than 0.1 microns sq sec 10 microgal and agreement with previous measurements is within the combined uncertainties of the measurements.

  6. Familial Aggregation of Absolute Pitch

    PubMed Central

    Baharloo, Siamak; Service, Susan K.; Risch, Neil; Gitschier, Jane; Freimer, Nelson B.

    2000-01-01

    Absolute pitch (AP) is a behavioral trait that is defined as the ability to identify the pitch of tones in the absence of a reference pitch. AP is an ideal phenotype for investigation of gene and environment interactions in the development of complex human behaviors. Individuals who score exceptionally well on formalized auditory tests of pitch perception are designated as “AP-1.” As described in this report, auditory testing of siblings of AP-1 probands and of a control sample indicates that AP-1 aggregates in families. The implications of this finding for the mapping of loci for AP-1 predisposition are discussed. PMID:10924408

  7. Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner.

    PubMed

    Holmgaard, Rikke B; Zamarin, Dmitriy; Li, Yanyun; Gasmi, Billel; Munn, David H; Allison, James P; Merghoub, Taha; Wolchok, Jedd D

    2015-10-13

    Indoleamine 2,3-dioxygenase (IDO) has been described as a major mechanism of immunosuppression in tumors, though the mechanisms of this are poorly understood. Here, we find that expression of IDO by tumor cells results in aggressive tumor growth and resistance to T-cell-targeting immunotherapies. We demonstrate that IDO orchestrates local and systemic immunosuppressive effects through recruitment and activation of myeloid-derived suppressor cells (MDSCs), through a mechanism dependent on regulatory T cells (Tregs). Supporting these findings, we find that IDO expression in human melanoma tumors is strongly associated with MDSC infiltration. Treatment with a selective IDO inhibitor in vivo reversed tumor-associated immunosuppression by decreasing numbers of tumor-infiltrating MDSCs and Tregs and abolishing their suppressive function. These findings establish an important link between IDO and multiple immunosuppressive mechanisms active in the tumor microenvironment, providing a strong rationale for therapeutic targeting of IDO as one of the central regulators of immune suppression.

  8. Disentangling Tfr cells from Treg cells and Tfh cells: How to untie the Gordian knot.

    PubMed

    Amiezer, Mayan; Phan, Tri Giang

    2016-05-01

    T follicular regulatory (Tfr) cells are a subpopulation of Treg cells that have adopted the T follicular helper cell program to localize to the B-cell follicle. Because of the difficulties in generating mouse models in which Tfr cells are selectively affected, determining where and how Tfr cells regulate the germinal center response remains to be resolved. In this issue of the European Journal of Immunology, Dent and colleagues [Eur. J. Immunol. 2016. 46: 1152-1161] describe a simple, elegant mouse model to conditionally delete Tfr cells without impacting on the Treg- and Tfh-cell populations. Their initial studies suggest that Tfr cells have a more complex role than previously thought, particularly with respect to the regulation of immunoglobulin isotype switching to IgA. PMID:27109022

  9. Disentangling Tfr cells from Treg cells and Tfh cells: How to untie the Gordian knot.

    PubMed

    Amiezer, Mayan; Phan, Tri Giang

    2016-05-01

    T follicular regulatory (Tfr) cells are a subpopulation of Treg cells that have adopted the T follicular helper cell program to localize to the B-cell follicle. Because of the difficulties in generating mouse models in which Tfr cells are selectively affected, determining where and how Tfr cells regulate the germinal center response remains to be resolved. In this issue of the European Journal of Immunology, Dent and colleagues [Eur. J. Immunol. 2016. 46: 1152-1161] describe a simple, elegant mouse model to conditionally delete Tfr cells without impacting on the Treg- and Tfh-cell populations. Their initial studies suggest that Tfr cells have a more complex role than previously thought, particularly with respect to the regulation of immunoglobulin isotype switching to IgA.

  10. The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases

    PubMed Central

    Park, Benjamin V.; Pan, Fan

    2015-01-01

    Nuclear receptors play an essential role in cellular environmental sensing, differentiation, development, homeostasis, and metabolism and are thus highly conserved across multiple species. The anti-inflammatory role of nuclear receptors in immune cells has recently gained recognition. Nuclear receptors play critical roles in both myeloid and lymphoid cells, particularly in helper CD4+ T-cell type 17 (Th17) and regulatory T cells (Treg). Th17 and Treg have a major impact on cellular fate through their interactions with cytokine signaling pathways. Recent studies have emphasized the interactions between nuclear receptors and the known cytokine signals and how these interactions affect the expression and function of master transcription factors in Th17 and Treg subsets. This review will focus on the most recent discoveries concerning the roles of nuclear receptors in regulating the Th17/Treg cell-fate determination. PMID:25958843

  11. Multisite Comparison of CD4 and CD8 T-Lymphocyte Counting by Single- versus Multiple-Platform Methodologies: Evaluation of Beckman Coulter Flow-Count Fluorospheres and the tetraONE System

    PubMed Central

    Reimann, Keith A.; O'Gorman, Maurice R. G.; Spritzler, John; Wilkening, Cynthia L.; Sabath, Daniel E.; Helm, Karen; Campbell, Donald E.

    2000-01-01

    New analytic methods that permit absolute CD4 and CD8 T-cell determinations to be performed entirely on the flow cytometer have the potential for improving assay precision and accuracy. In a multisite trial, we compared two different single-platform assay methods with a predicate two-color assay in which the absolute lymphocyte count was derived by conventional hematology. A two-color method employing lymphocyte light scatter gating and Beckman Coulter Flow-Count fluorospheres for absolute counting produced within-laboratory precision equivalent to that of the two-color predicate method, as measured by coefficient of variation of replicate measurements. The fully automated Beckman Coulter tetraONE System four-color assay employing CD45 lymphocyte gating, automated analysis, and absolute counting by fluorospheres resulted in a small but significant improvement in the within-laboratory precision of CD4 and CD8 cell counts and percentages suggesting that the CD45 lymphocyte gating and automated analysis might have contributed to the improved performance. Both the two-color method employing Flow-Count fluorospheres and the four-color tetraONE System provided significant and substantial improvements in between-laboratory precision of absolute counts. In some laboratories, absolute counts obtained by the single-platform methods showed small but consistent differences relative to the predicate method. Comparison of each laboratory's absolute counts with the five-laboratory median value suggested that these differences resulted from a bias in the absolute lymphocyte count obtained from the hematology instrument in some laboratories. These results demonstrate the potential for single-platform assay methods to improve within-laboratory and between-laboratory precision of CD4 and CD8 T-cell determinations compared with conventional assay methods. PMID:10799444

  12. Fast counting electronics for neutron coincidence counting

    DOEpatents

    Swansen, James E.

    1987-01-01

    An amplifier-discriminator is tailored to output a very short pulse upon an above-threshold input from a detector which may be a .sup.3 He detector. The short pulse output is stretched and energizes a light emitting diode (LED) to provide a visual output of operation and pulse detection. The short pulse is further fed to a digital section for processing and possible ORing with other like generated pulses. Finally, the output (or ORed output ) is fed to a derandomizing buffer which converts the rapidly and randomly occurring pulses into synchronized and periodically spaced-apart pulses for the accurate counting thereof. Provision is also made for the internal and external disabling of each individual channel of amplifier-discriminators in an ORed plurality of same.

  13. Fast counting electronics for neutron coincidence counting

    DOEpatents

    Swansen, J.E.

    1985-03-05

    An amplifier-discriminator is tailored to output a very short pulse upon an above-threshold input from a detector which may be a /sup 3/He detector. The short pulse output is stretched and energizes a light emitting diode (LED) to provide a visual output of operation and pulse detection. The short pulse is further fed to a digital section for processing and possible ORing with other like generated pulses. Finally, the output (or ORed output) is fed to a derandomizing buffer which converts the rapidly and randomly occurring pulses into synchronized and periodically spaced-apart pulses for the accurate counting thereof. Provision is also made for the internal and external disabling of each individual channel of amplifier-discriminators in an ORed plurality of same.

  14. Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood

    PubMed Central

    Su, Laura F.; del Alcazar, Daniel; Stelekati, Erietta; Wherry, E. John; Davis, Mark M.

    2016-01-01

    The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities of Tregs outside the context of transgenic TCRs are largely unknown. Using peptide–MHC tetramers, we isolated rare specific Foxp3+ cells directly ex vivo from adult peripheral blood and defined their frequency and phenotype. We find that a proportion of circulating Tregs recognize foreign antigens and the frequency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection. In contrast, the frequencies of Tregs that recognize some common microbial antigens are significantly reduced in the blood of most adults. Exposure to peripheral antigens likely has a major influence on the balance between Tregs and conventional T-cell subsets because a larger proportion of flu-specific T cells has a regulatory cell phenotype in the cord blood. Consistent with this finding, we show that lymphocytic choriomeningitis virus infection can directly modulate the ratio of virus-specific effectors and Tregs in mice. The resulting change in the balance within an antigen-specific T-cell population further correlates with the magnitude of effector response and the chronicity of infection. Taken together, our data highlight the importance of antigen specificity in the functional dynamics of the T-cell repertoire. Each specific population of CD4+ T cells in human peripheral blood contains a subset of Tregs at birth, but the balance between regulatory and effector subsets changes in response to peripheral antigen exposure and this could impact the robustness of antipathogen immunity. PMID:27681619

  15. Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis

    PubMed Central

    2013-01-01

    Background Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. Results We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. Conclusions The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms. PMID:24564794

  16. Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

    PubMed

    Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

    2015-01-01

    Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression.

  17. Impact of dietary components on NK and Treg cell function for cancer prevention.

    PubMed

    Kim, Young S; Sayers, Thomas J; Colburn, Nancy H; Milner, John A; Young, Howard A

    2015-09-01

    An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation of regulatory T (Treg) cells. Evidence exists that components in commonly consumed foods including vitamins A, D, and E, water-soluble constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty acids in fish oil can modulate NK cell activities, Treg cell properties, and the interactions between those two cell types. Thus, it is extremely important for cancer prevention to understand the involvement of dietary components with the early stage dynamics of interactions among these immune cells. This review addresses the potential significance of diet in supporting the function of NK cells, Treg cells, and the balance between those two cell types, which ultimately results in decreased cancer risk. PMID:25845339

  18. Novel CD8+ Treg suppress EAE by TGF-β- and IFN-γ-dependent mechanisms

    PubMed Central

    Chen, Mei-Ling; Yan, Bo-Shiun; Kozoriz, Deneen; Weiner, Howard L.

    2010-01-01

    Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP− counterparts. In addition to TGF-β, CD8+LAP+ cells produce IFN-γ, and these cells suppress EAE that is dependent on both TGF-β and IFN-γ. In an adoptive co-transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-γ production in vivo. Furthermore, in vivo neutralization of IFN-γ and studies with IFN-γ-deficient mice demonstrate an important role for IFN-γ production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes. PMID:19768696

  19. Impact of Dietary Components on NK and Treg Cell Function for Cancer Prevention

    PubMed Central

    Sayers, Thomas J.; Colburn, Nancy H.; Milner, John A.; Young, Howard A.

    2015-01-01

    An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation of regulatory T (Treg) cells. Evidence exists that components in commonly consumed foods including vitamins A, D, and E, water-soluble constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty acids in fish oil can modulate NK cell activities, Treg cell properties, and the interactions between those two cell types. Thus, it is extremely important for cancer prevention to understand the involvement of dietary components with the early stage dynamics of interactions among these immune cells. This review addresses the potential significance of diet in supporting the function of NK cells, Treg cells, and the balance between those two cell types, which ultimately results in decreased cancer risk. PMID:25845339

  20. A differential interplay between the expression of Th1/Th2/Treg related cytokine genes in Teladorsagia circumcincta infected DRB1*1101 carrier lambs

    PubMed Central

    2011-01-01

    Substantial debate exists on whether the immune response between sheep resistant and susceptible to gastrointestinal nematodes can be differentiated into a Th1 and Th2 phenotype. The present study addresses the hypothesis that variation in resistance to Teladorsagia circumcincta between DRB1*1101 (associated with reduced faecal egg count and worm burden) carriers and non-carriers is due to a differential interplay in the expression of Th1/Th2 and regulatory T (Treg) related cytokine genes. Lambs from each genotype were either slaughtered at day 0 (un-infected control) or infected with 3 × 104 Teladorsagia circumcincta L3 and slaughtered at 3, 7, 21, and 35 days later. Lambs carrying the DRB1*1101 allele had a significantly lower worm burden (P < 0.05) compared to the non-carriers. Abomasal mucosal cytokine gene expression was evaluated by quantitative real-time PCR and comparison made for time and genotype effects. The response generated varied through the course of infection and was affected by genotype. DRB1*1101 carriers had an up-regulated expression of the Th1-related cytokine genes (IL-1β, TNFα, and IFN-γ) at day 3, but this was replaced by an up-regulated expression of Th2-related cytokine genes (IL-10 and IL-13) and Treg-related cytokine genes (IL-2RA-CD25, TGFα, TGFβ, Arg2, MIF and FOXP3) by day 7. Conversely, in the non-carriers these changes in gene expression were delayed until days 7 and 21 post infection (pi), respectively. It is concluded that resistance to Teladorsagia circumcincta in animals carrying the DRB1*1101 allele is influenced by an earlier interplay between Th1, Th2 and T regulatory immune response genes. PMID:21385411

  1. Photon counting digital holography

    NASA Astrophysics Data System (ADS)

    Demoli, Nazif; Skenderović, Hrvoje; Stipčević, Mario; Pavičić, Mladen

    2016-05-01

    Digital holography uses electronic sensors for hologram recording and numerical method for hologram reconstruction enabling thus the development of advanced holography applications. However, in some cases, the useful information is concealed in a very wide dynamic range of illumination intensities and successful recording requires an appropriate dynamic range of the sensor. An effective solution to this problem is the use of a photon-counting detector. Such detectors possess counting rates of the order of tens to hundreds of millions counts per second, but conditions of recording holograms have to be investigated in greater detail. Here, we summarize our main findings on this problem. First, conditions for optimum recording of digital holograms for detecting a signal significantly below detector's noise are analyzed in terms of the most important holographic measures. Second, for time-averaged digital holograms, optimum recordings were investigated for exposures shorter than the vibration cycle. In both cases, these conditions are studied by simulations and experiments.

  2. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses

    PubMed Central

    Lu, Li-Fan; Boldin, Mark P.; Chaudhry, Ashutosh; Lin, Ling-Li; Taganov, Konstantin D.; Hanada, Toshikatsu; Yoshimura, Akihiko; Baltimore, David; Rudensky, Alexander Y.

    2010-01-01

    Summary Foxp3+ regulatory T (Treg) cells maintain immune homeostasis by limiting different types of inflammatory responses. Here, we report that miR-146a, one of the miRNAs prevalently expressed in Treg cells, is critical for their suppressor function. The deficiency of miR-146a in Treg cells resulted in a breakdown of immunological tolerance manifested in a fatal IFNγ-dependent immune-mediated lesions in a variety of organs. This was likely due to augmented expression and activation of signal transducer and activator transcription 1 (Stat1), a direct target of miR146a. Likewise, heightened Stat1 activation in Treg cells subjected to a selective ablation of SOCS1, a key negative regulator of Stat1 phosphorylation downstream of IFNγ receptor, was associated with analogous Th1-mediated pathology. Our results suggest that specific aspects of Treg suppressor function are controlled by a single miRNA and that an optimal range of Stat1 activation is important for Treg-mediated control of Th1 responses and associated autoimmunity. PMID:20850013

  3. The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology.

    PubMed

    Hall, Aisling O'Hara; Beiting, Daniel P; Tato, Cristina; John, Beena; Oldenhove, Guillaume; Lombana, Claudia Gonzalez; Pritchard, Gretchen Harms; Silver, Jonathan S; Bouladoux, Nicolas; Stumhofer, Jason S; Harris, Tajie H; Grainger, John; Wojno, Elia D Tait; Wagage, Sagie; Roos, David S; Scott, Philip; Turka, Laurence A; Cherry, Sara; Reiner, Steven L; Cua, Daniel; Belkaid, Yasmine; Elloso, M Merle; Hunter, Christopher A

    2012-09-21

    Interferon-γ (IFN-γ) promotes a population of T-bet(+) CXCR3(+) regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-γ in the periphery but on IL-27 at mucosal sites. Transfer of Treg cells ameliorated the infection-induced pathology observed in Il27(-/-) mice, and this was dependent on their ability to produce IL-10. Microarray analysis revealed that Treg cells exposed to either IFN-γ or IL-27 have distinct transcriptional profiles. Thus, IFN-γ and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation.

  4. Engineering an "infectious" T(reg) biomimetic through chemoselective tethering of TGF-β1 to PEG brush surfaces.

    PubMed

    Yang, E Y; Kronenfeld, J P; Gattás-Asfura, K M; Bayer, A L; Stabler, C L

    2015-10-01

    Modulation of immunological responses to allografts following transplantation is of pivotal importance to improving graft outcome and duration. Of the many approaches, harnessing the dominant tolerance induced by regulatory T cells (Treg) holds tremendous promise. Recent studies have highlighted the unique potency of cell surface-bound TGF-β1 on Treg for promoting infectious tolerance, i.e. to confer suppressive capacity from one cell to another. To mimic this characteristic, TGF-β1 was chemoselectively tethered to inert and viable polymer grafting platforms using Staudinger ligation. We report the synthesis and functional characterization of these engineered TGF-β1 surfaces. Inert beads tethered with TGF-β1 were capable of efficiently converting naïve CD4(+) CD62L(hi) T cells to functional Treg. Concordantly, translation of conjugation scheme from inert surfaces to viable cells also led to efficient generation of functional Treg. Further, the capacity of these platforms to generate antigen-specific Treg was demonstrated. These findings illustrate the unique faculty of tethered TGF-β1 biomaterial platforms to function as an "infectious" Treg and provide a compelling approach for generating tolerogenic microenvironments for allograft transplantation. PMID:26197412

  5. TLR4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation

    PubMed Central

    Cao, Anthony T.; Yao, Suxia; Stefka, Andrew T.; Liu, Zhanju; Qin, Hongwei; Liu, Houpu; Evans-Marin, Heather L.; Elson, Charles O.; Nagler, Cathryn R.; Cong, Yingzi

    2014-01-01

    Tregs play a crucial role in the maintenance of intestinal immune homeostasis. However, significant numbers of Foxp3+ Tregs accumulate in the inflamed lesions in experimental colitis and in IBD patients. Treg production of the proinflammatory cytokines IFN-γ and/or IL-17 may arguably explain their ineffectiveness in suppressing intestinal inflammation. However, it remains unknown whether iTreg and tTreg produce proinflammatory cytokines and how TLR signaling regulates this process. Here, we found that Foxp3+Tregs were increased in the intestines of B6.TLR4−/− and B6.IL-10−/− mice when compared with WT B6 mice. TLR4−/− and IL-10−/− resulted in more Tregs within inflamed intestines. The majority of Foxp3+ Tregs in the spleen was Helios+Nrp1+, whereas most Foxp3+ Tregs in the intestinal LP were Helios−Nrp1−. More Helios+Nrp1+ Tregs expressed IFN-γ and/or IL-17 than did Helios−Nrp1− Tregs in the spleen and intestine, which was increased with TLR4−/−. TLR4 signaling in T cells and APCs inhibited Foxp3+ induction via MyD88-dependent, TRIF-independent pathways, which was negatively regulated by SOCS3. Collectively, these data demonstrate Helios+Nrp1+ tTregs and Helios−Nrp1− iTregs produce proinflammatory cytokines in the intestines during inflammation, which was regulated by TLR4 signaling. PMID:25015957

  6. Extracellular purine metabolism and signaling of CD73-derived adenosine in murine Treg and Teff cells.

    PubMed

    Romio, Michael; Reinbeck, Benjamin; Bongardt, Sabine; Hüls, Sandra; Burghoff, Sandra; Schrader, Jürgen

    2011-08-01

    CD73-derived adenosine acts as potent inhibitor of inflammation, and regulatory T cells (Treg) have been shown to express CD73 as a novel marker. This study explored the role of endogenously formed adenosine in modulating NF-κB activity and cytokine/chemokine release from murine Treg and effector T cells (Teff) including key enzymes/purinergic receptors of extracellular ATP catabolism. Stimulating murine splenocytes and CD4(+) T cells with anti-CD3/anti-CD28 significantly upregulated activated NF-κB in CD73(-/-) T cells (wild type: 4.36 ± 0.21; CD73(-/-): 6.58 ± 0.75; n = 4; P = 0.029). This was associated with an augmented release of proinflammatory cytokines IL-2, TNF-α, and IFN-γ. Similar changes were observed with the CD73 inhibitor APCP (50 μM) on NF-κB and IFN-γ in wild-type CD4(+) T-cells. Treatment of stimulated CD4(+) T-cells with adenosine (25 μM) potently reduced IFN-γ release which is mediated by adenosine A2a receptors (A2aR). AMP (50 μM) also reduced cytokine release which was not inhibited by APCP. In Teff, A2aR activation (CGS21680) potently inhibited the release of IL-1, IL-2, IL-3, IL-4, IL-12, IL-13, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), CCL3, and CCL4. However, in Treg, CGS21680 did not alter cytokine/chemokine release. In summary, CD73-derived adenosine tonically inhibits active NF-κB in CD4(+) T-cells, thereby modulating the release of a broad spectrum of proinflammatory cytokines and chemokines. Downregulation of P2X7 and upregulation of CD73 in Treg after antigenic stimulation may be an important mechanism to maintain the ability of Treg to generate immunosuppressive adenosine.

  7. Cosmology with negative absolute temperatures

    NASA Astrophysics Data System (ADS)

    Vieira, J. P. P.; Byrnes, Christian T.; Lewis, Antony

    2016-08-01

    Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion (w < ‑1) with no Big Rip, and their contracting counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.

  8. Apparatus for absolute pressure measurement

    NASA Technical Reports Server (NTRS)

    Hecht, R. (Inventor)

    1969-01-01

    An absolute pressure sensor (e.g., the diaphragm of a capacitance manometer) was subjected to a superimposed potential to effectively reduce the mechanical stiffness of the sensor. This substantially increases the sensitivity of the sensor and is particularly useful in vacuum gauges. An oscillating component of the superimposed potential induced vibrations of the sensor. The phase of these vibrations with respect to that of the oscillating component was monitored, and served to initiate an automatic adjustment of the static component of the superimposed potential, so as to bring the sensor into resonance at the frequency of the oscillating component. This establishes a selected sensitivity for the sensor, since a definite relationship exists between resonant frequency and sensitivity.

  9. Cosmology with negative absolute temperatures

    NASA Astrophysics Data System (ADS)

    Vieira, J. P. P.; Byrnes, Christian T.; Lewis, Antony

    2016-08-01

    Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion (w < -1) with no Big Rip, and their contracting counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.

  10. What Counts as Evidence?

    ERIC Educational Resources Information Center

    Dougherty Stahl, Katherine A.

    2014-01-01

    Each disciplinary community has its own criteria for determining what counts as evidence of knowledge in their academic field. The criteria influence the ways that a community's knowledge is created, communicated, and evaluated. Situating reading, writing, and language instruction within the content areas enables teachers to explicitly…

  11. WY Kids Count.

    ERIC Educational Resources Information Center

    Wyoming Kids Count, Cheyenne.

    This WY Kids Count brochure uses the metaphor of children's building blocks to present information on the current well-being of Wyoming children and to advocate enhancing the lives of young children. Each block (i.e., each develop the brochure) presents concerns in a separate area: (1) poverty, highlighting the number of children living in…

  12. Counting Tech Prep Students.

    ERIC Educational Resources Information Center

    Barnett, Elizabeth

    2002-01-01

    Discusses the problems surrounding the counting of tech prep students. Suggests that one problem is the lack of a single definition for the term "tech prep." Suggests that if it is to be evaluated as a program, it needs more resources. (JOW)

  13. Accounting for What Counts

    ERIC Educational Resources Information Center

    Milner, Joseph O.; Ferran, Joan E.; Martin, Katharine Y.

    2003-01-01

    No Child Left Behind legislation makes it clear that outside evaluators determine what gets taught in the classroom. It is important to ensure they measure what truly counts in school. This fact is poignantly and sadly true for the under funded, poorly resourced, "low performing" schools that may be hammered by administration accountants in the…

  14. LOW ENERGY COUNTING CHAMBERS

    DOEpatents

    Hayes, P.M.

    1960-02-16

    A beta particle counter adapted to use an end window made of polyethylene terephthalate was designed. The extreme thinness of the film results in a correspondingly high transmission of incident low-energy beta particles by the window. As a consequence, the counting efficiency of the present counter is over 40% greater than counters using conventional mica end windows.

  15. Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer

    PubMed Central

    Li, Kai; Chen, Fuchao; Xie, Huijuan

    2016-01-01

    Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated. The infiltration of FOXP3+ and GARP+ Tregs in 102 patients with advanced GC who were treated with or without NACT was measured using immunohistochemical method. The infiltration of FOXP3+ and GARP+ Tregs was significantly decreased in the NACT group than in the non-NACT group (P=0.023 and P=0.012, respectively) and significantly associated with tumor, node, metastasis stage (P=0.019 and P=0.011, respectively). There was no significant difference in patient’s overall survival between the NACT and non-NACT groups (P=0.166); however, patients in the NACT group with decreased infiltration of FOXP3+ and GARP+ Tregs had longer overall survival (P=0.002 and P<0.001, respectively). Univariate and multivariate analyses indicated that the infiltration of GARP+ Tregs and lymph node metastasis were independent prognostic factors (P=0.038 and P=0.013, respectively). The results demonstrated that NACT could decrease the infiltration of FOXP3+ and GARP+ Tregs, and that the infiltration of GARP+ Tregs may serve as a new prognostic factor of human GC response to NACT. PMID:27366089

  16. Measurement of Absolute Carbon Isotope Ratios: Mechanisms and Implications

    NASA Astrophysics Data System (ADS)

    Vogel, J. S.; Giacomo, J. A.; Dueker, S. R.

    2012-12-01

    An accelerator mass spectrometer (AMS) produced absolute isotope ratio measurements for 14C/13C as tested against >500 samples of NIST SRM-4990-C (OxII 14C standard) to an accuracy of 2.2±0.6‰ over a period of one year with measurements made to 1% counting statistics. The spectrometer is not maximized for 13C/12C, but measured ∂13C to 0.4±0.1‰ accuracy, with known methods for improvement. An AMS produces elemental anions from a sputter ion source and includes a charge-changing collision in a gas cell to isolate the rare 14C from the common isotopes and molecular isobars. Both these physical processes have been modeled to determine the parameters providing such absolute measures. Neutral resonant ionization in a cesium plasma produces mass-independent ionization, while velocity dependent charge-state distributions in gas collisions produce relative ion beam intensities that are linear in mass at specific collision energies. The mechanisms are not specific to carbon isotopes, but stand alone absolute IRMS (AIR-MS) instruments have not yet been made. Aside from the obvious applications in metrology, AIR-MS is particularly valuable in coupled separatory MS because no internal or external standards are required. Sample definition processes can be compared, even if no exact standard reference sample exists. Isotope dilution measurements do not require standards matching the dilution end-points and can be made over an extended, even extrapolated, range.

  17. Absolute configuration of isovouacapenol C

    PubMed Central

    Fun, Hoong-Kun; Yodsaoue, Orapun; Karalai, Chatchanok; Chantrapromma, Suchada

    2010-01-01

    The title compound, C27H34O5 {systematic name: (4aR,5R,6R,6aS,7R,11aS,11bR)-4a,6-dihy­droxy-4,4,7,11b-tetra­methyl-1,2,3,4,4a,5,6,6a,7,11,11a,11b-dodeca­hydro­phenanthro[3,2-b]furan-5-yl benzoate}, is a cassane furan­oditerpene, which was isolated from the roots of Caesalpinia pulcherrima. The three cyclo­hexane rings are trans fused: two of these are in chair conformations with the third in a twisted half-chair conformation, whereas the furan ring is almost planar (r.m.s. deviation = 0.003 Å). An intra­molecular C—H⋯O inter­action generates an S(6) ring. The absolute configurations of the stereogenic centres at positions 4a, 5, 6, 6a, 7, 11a and 11b are R, R, R, S, R, S and R, respectively. In the crystal, mol­ecules are linked into infinite chains along [010] by O—H⋯O hydrogen bonds. C⋯O [3.306 (2)–3.347 (2) Å] short contacts and C—H⋯π inter­actions also occur. PMID:21588364

  18. Frequency-domain analysis of absolute gravimeters

    NASA Astrophysics Data System (ADS)

    Svitlov, S.

    2012-12-01

    An absolute gravimeter is analysed as a linear time-invariant system in the frequency domain. Frequency responses of absolute gravimeters are derived analytically based on the propagation of the complex exponential signal through their linear measurement functions. Depending on the model of motion and the number of time-distance coordinates, an absolute gravimeter is considered as a second-order (three-level scheme) or third-order (multiple-level scheme) low-pass filter. It is shown that the behaviour of an atom absolute gravimeter in the frequency domain corresponds to that of the three-level corner-cube absolute gravimeter. Theoretical results are applied for evaluation of random and systematic measurement errors and optimization of an experiment. The developed theory agrees with known results of an absolute gravimeter analysis in the time and frequency domains and can be used for measurement uncertainty analyses, building of vibration-isolation systems and synthesis of digital filtering algorithms.

  19. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

    PubMed Central

    Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  20. Epigenetic modification of the FoxP3 TSDR in HAM/TSP decreases the functional suppression of Tregs.

    PubMed

    Anderson, Monique R; Enose-Akahata, Yoshimi; Massoud, Raya; Ngouth, Nyater; Tanaka, Yuetsu; Oh, Unsong; Jacobson, Steven

    2014-09-01

    HTLV-1 is a human retrovirus that is associated with the neuroinflammatory disorder HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In these patients, HTLV-1 is primarily found in the CD4(+)CD25(+) T cell subset (Regulatory T cells:Tregs), which is responsible for peripheral immune tolerance and is known to be dysfunctional in HAM/TSP. Recent evidence suggests that FoxP3 expression and function is determined epigenetically through DNA demethylation in the Treg-specific demethylated region (TSDR). We analyzed the methylation of the TSDR in PBMCs, CD4(+) T cells, and CD4(+)CD25(+) T cells from normal healthy donors (NDs) and HAM/TSP patients. We demonstrated that there is decreased demethylation in analyzed PBMCs and CD4(+)CD25(+) T cells from HAM/TSP patients as compared to NDs. Furthermore, decreased TSDR demethylation was associated with decreased functional suppression by Tregs. Additionally, increased HTLV-1 Tax expression in HAM/TSP PBMC culture correlated with a concomitant decline in FoxP3 TSDR demethylation. Overall, we suggest that HTLV-1 infection decreases Treg functional suppressive capacity in HAM/TSP through modification of FoxP3 TSDR demethylation and that dysregulated Treg function may contribute to HAM/TSP disease pathogenesis. PMID:24845974

  1. Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis by modulating Th17/Treg imbalance in a murine model.

    PubMed

    Wang, Linyuan; Guan, Ning; Jin, Ying; Lin, Xiaoping; Gao, Hong

    2015-03-01

    To date, Porphyromonas gingivalis (P. gingivalis) vaccination has been studied only in animals, and no effective prophylactic human periodontal vaccine has been developed, with the reason for the failure of prophylactic human periodontal vaccines unknown. T helper 17 cell (Th17)/regulatory T (Treg) cell responses play an important role in the development of periodontitis, and a Th17/Treg imbalance causes the pathogenesis of periodontitis. However, whether vaccination with P. gingivalis can prevent periodontitis through modulation of the Th17/Treg imbalance remains unknown. In this study, mice were subcutaneously vaccinated with formalin-killed P. gingivalis and then orally challenged with P. gingivalis. The vaccination protected the mice from alveolar bone resorption and inflammation. These protective effects might be ascribed to downregulation of Th17 cells and interleukin (IL)-17A production, upregulation of Treg and receptor activator of nuclear factor-kappa B ligand (RANKL)(+)CD4(+)T cells, and IL-10 and transforming growth factor-β1 production, and inhibition of lymphocyte proliferation. Our findings may provide a direction for the development of a vaccine or therapy against periodontitis by alteration of the Th17/Treg imbalance.

  2. CD39 expression on Treg and Th17 cells is associated with metabolic factors in patients with type 2 diabetes.

    PubMed

    Cortez-Espinosa, Nancy; Cortés-Garcia, Juan Diego; Martínez-Leija, Ernesto; Rodríguez-Rivera, Jose Guillermo; Barajas-López, Carlos; González-Amaro, Roberto; Portales-Pérez, Diana Patricia

    2015-09-01

    Th17 cells are involved in the pathogenesis of multiple inflammatory diseases such as type two diabetes (T2D). CD39(+) Treg cells have been implicated as responsible for suppressing Th17 cells. The aim of this study was to evaluate the number and function of CD4(+)CD25(high)CD39(+) Treg and Th17 cells in peripheral blood mononuclear cells (PBMC) from T2D patients and healthy control subjects. The Th17 cells were detected in PBMC under culture with human anti-CD3/CD28 and PMA/ionomycin and the levels of IL-17 were assessed by ELISA and qPCR. The T2D patients with obesity showed significantly lower percentages of CD39(+) Treg cells. A negative correlation between CD39(+) Treg cells and weight, and body mass index was detected. In contrast, the low levels of CD4(+)IL-17(+) cells in overweight and obese T2D patients showed a positive correlation with glucose and HbA1c. Additionally, we found a subpopulation of Th17 cells that express CD39 and were correlated with glucose and HbA1c. Our findings suggest that the expression of CD39 on Treg cells and also in CD4(+)IL-17(+) cells from T2D patients is related to hyperglycemia as well as to overweight and obesity and therefore may participate as a modulator of the effector capacity of Th17 cells.

  3. Microbiota-Specific CD4CD8αα Tregs: Role in Intestinal Immune Homeostasis and Implications for IBD.

    PubMed

    Sarrabayrouse, Guillaume; Alameddine, Joudy; Altare, Frédéric; Jotereau, Francine

    2015-01-01

    In studies in murine models, active suppression by IL-10-secreting Foxp3 regulatory T cells (Tregs) has emerged as an essential mechanism in colon homeostasis. However, the role of the equivalent subset in humans remains unclear, leading to suggestions that other subsets and/or mechanisms may substitute for Foxp3 Tregs in the maintenance of colon homeostasis. We recently described a new subset of CD4CD8αα T cells reactive to the gut bacterium Faecalibacterium prausnitzii and endowed with regulatory/suppressive functions. This subset is abundant in the healthy colonic mucosa, but less common in that of patients with inflammatory bowel disease (IBD). We discuss here the physiological significance and potential role of these Tregs in preventing inflammation of the gut mucosa and the potential applications of these discoveries for IBD management.

  4. Absolute Income, Relative Income, and Happiness

    ERIC Educational Resources Information Center

    Ball, Richard; Chernova, Kateryna

    2008-01-01

    This paper uses data from the World Values Survey to investigate how an individual's self-reported happiness is related to (i) the level of her income in absolute terms, and (ii) the level of her income relative to other people in her country. The main findings are that (i) both absolute and relative income are positively and significantly…

  5. Investigating Absolute Value: A Real World Application

    ERIC Educational Resources Information Center

    Kidd, Margaret; Pagni, David

    2009-01-01

    Making connections between various representations is important in mathematics. In this article, the authors discuss the numeric, algebraic, and graphical representations of sums of absolute values of linear functions. The initial explanations are accessible to all students who have experience graphing and who understand that absolute value simply…

  6. Preschoolers' Success at Coding Absolute Size Values.

    ERIC Educational Resources Information Center

    Russell, James

    1980-01-01

    Forty-five 2-year-old and forty-five 3-year-old children coded relative and absolute sizes using 1.5-inch, 6-inch, and 18-inch cardboard squares. Results indicate that absolute coding is possible for children of this age. (Author/RH)

  7. Introducing the Mean Absolute Deviation "Effect" Size

    ERIC Educational Resources Information Center

    Gorard, Stephen

    2015-01-01

    This paper revisits the use of effect sizes in the analysis of experimental and similar results, and reminds readers of the relative advantages of the mean absolute deviation as a measure of variation, as opposed to the more complex standard deviation. The mean absolute deviation is easier to use and understand, and more tolerant of extreme…

  8. Monolithically integrated absolute frequency comb laser system

    DOEpatents

    Wanke, Michael C.

    2016-07-12

    Rather than down-convert optical frequencies, a QCL laser system directly generates a THz frequency comb in a compact monolithically integrated chip that can be locked to an absolute frequency without the need of a frequency-comb synthesizer. The monolithic, absolute frequency comb can provide a THz frequency reference and tool for high-resolution broad band spectroscopy.

  9. Estimating the absolute wealth of households

    PubMed Central

    Gerkey, Drew; Hadley, Craig

    2015-01-01

    Abstract Objective To estimate the absolute wealth of households using data from demographic and health surveys. Methods We developed a new metric, the absolute wealth estimate, based on the rank of each surveyed household according to its material assets and the assumed shape of the distribution of wealth among surveyed households. Using data from 156 demographic and health surveys in 66 countries, we calculated absolute wealth estimates for households. We validated the method by comparing the proportion of households defined as poor using our estimates with published World Bank poverty headcounts. We also compared the accuracy of absolute versus relative wealth estimates for the prediction of anthropometric measures. Findings The median absolute wealth estimates of 1 403 186 households were 2056 international dollars per capita (interquartile range: 723–6103). The proportion of poor households based on absolute wealth estimates were strongly correlated with World Bank estimates of populations living on less than 2.00 United States dollars per capita per day (R2 = 0.84). Absolute wealth estimates were better predictors of anthropometric measures than relative wealth indexes. Conclusion Absolute wealth estimates provide new opportunities for comparative research to assess the effects of economic resources on health and human capital, as well as the long-term health consequences of economic change and inequality. PMID:26170506

  10. Absolute optical metrology : nanometers to kilometers

    NASA Technical Reports Server (NTRS)

    Dubovitsky, Serge; Lay, O. P.; Peters, R. D.; Liebe, C. C.

    2005-01-01

    We provide and overview of the developments in the field of high-accuracy absolute optical metrology with emphasis on space-based applications. Specific work on the Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor is described along with novel applications of the sensor.

  11. IL-35, an anti-inflammatory cytokine which expands CD4+CD25+ Treg Cells.

    PubMed

    Castellani, Maria Luisa; Anogeianaki, A; Felaco, P; Toniato, E; De Lutiis, M A; Shaik, B; Fulcheri, M; Vecchiet, J; Tetè, S; Salini, V; Theoharides, T C; Caraffa, A; Antinolfi, P; Frydas, I; Conti, P; Cuccurullo, C; Ciampoli, C; Cerulli, G; Kempuraj, D

    2010-01-01

    Interleukin 12 (IL 12) p35/p40 is a heterodimeric cytokine which plays a critical role in inflammation, immunity and tissue proliferation, and also plays a relevant function in T helper (Th) cell polarization and Th1 T-cell differentiation. IL-12 family members, IL-12p70, IL-23, IL-27 and IL-35, play an important role in influencing helper T-cell differentiation. EBV-induced gene 3 can be associated with the p35 subunit of IL-12 to form the EBI3/p35 heterodimer, also called IL-35. It has been shown that IL-35 has biological activity and able to expand CD4+CD25+ Treg cells, suppress the proliferation of CD4+CD25- effector cells and inhibit Th17 cell polarization. IL-35 has been shown to be constitutively expressed by regulatory T (Treg) cells CD4(+)CD25(+)Foxp3(+) and suggested to contribute to their suppressive activity. IL-35 is a crucial mediator which provokes CD4+CD25+ T cell proliferation and IL-10 generation, another well-known anti-inflammatory cytokine, along with TGFbeta cytokine. These studies suggest that IL-35, together with other successfully discovered cytokine inhibitors, represents a new potential therapeutic cytokine for chronic inflammation, autoimmunity and other immunological disorders.

  12. The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector.

    PubMed

    Li, Rilun; Hu, Heng; Ma, Huiying; Chen, Long; Zhou, Binbin; Liu, Yinkun; Liang, Chunmin

    2013-10-01

    To explore the anti-tumor effect and immune mechanism mediated by a new recombinant adeno-associated virus (rAAV) encoding secondary lymphoid tissue chemokine (SLC) mature peptide gene. AAV Helper-Free system was used for rAAV-SLC package. The anti-tumor effect of SLC was detected by bearing tumor established from Hepal-6 cells both in C57BL/6J and nude mice. Flow cytometry analysis and IHC for Tumor-infiltrating T cells and CD11c+DCs were also investigated to explore the immunological mechanism. rAAV-SLC was successfully packaged in AAV293 cells and transfected Hepal-6 tumor cells at high efficiency. The anti-tumor effect was demonstrated by less tumor weight and longer survival outcome. Coincident with the anti-tumor response, local elaboration of SLC within the tumor bed elicited a heavy infiltration of CD4+, CD8+T cells and CD11c+ dendritic cells into the tumor sites. More importantly, there was higher infiltration of Foxp3+ regulatory T cells (Tregs). Local elaboration of SLC mediated by rAAV-SLC has strong T cell mediated anti-tumor effect. The study also suggested that Tregs in the tumor microenvironment tampered the anti-tumor effect.

  13. Counting RG flows

    DOE PAGES

    Gukov, Sergei

    2016-01-05

    Here, interpreting renormalization group flows as solitons interpolating between different fixed points, we ask various questions that are normally asked in soliton physics but not in renormalization theory. Can one count RG flows? Are there different "topological sectors" for RG flows? What is the moduli space of an RG flow, and how does it compare to familiar moduli spaces of (supersymmetric) dowain walls? Analyzing these questions in a wide variety of contexts -- from counting RG walls to AdS/CFT correspondence | will not only provide favorable answers, but will also lead us to a unified general framework that is powerfulmore » enough to account for peculiar RG flows and predict new physical phenomena. Namely, using Bott's version of Morse theory we relate the topology of conformal manifolds to certain properties of RG flows that can be used as precise diagnostics and "topological obstructions" for the strong form of the C-theorem in any dimension. Moreover, this framework suggests a precise mechanism for how the violation of the strong C-theorem happens and predicts "phase transitions" along the RG flow when the topological obstruction is non-trivial. Along the way, we also find new conformal manifolds in well-known 4d CFT's and point out connections with the superconformal index and classifying spaces of global symmetry groups.« less

  14. Normocaloric Low Cholesterol Diet Modulates Th17/Treg Balance in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Maggio, Roberta; Viscomi, Carmela; Andreozzi, Paola; D'Ettorre, Gabriella; Viscogliosi, Giovanni; Barbaro, Barbara; Gori, Manuele; Vullo, Vincenzo; Balsano, Clara

    2014-01-01

    Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in

  15. Absolute instability of the Gaussian wake profile

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart S.; Aggarwal, Arun K.

    1987-01-01

    Linear parallel-flow stability theory has been used to investigate the effect of viscosity on the local absolute instability of a family of wake profiles with a Gaussian velocity distribution. The type of local instability, i.e., convective or absolute, is determined by the location of a branch-point singularity with zero group velocity of the complex dispersion relation for the instability waves. The effects of viscosity were found to be weak for values of the wake Reynolds number, based on the center-line velocity defect and the wake half-width, larger than about 400. Absolute instability occurs only for sufficiently large values of the center-line wake defect. The critical value of this parameter increases with decreasing wake Reynolds number, thereby indicating a shrinking region of absolute instability with decreasing wake Reynolds number. If backflow is not allowed, absolute instability does not occur for wake Reynolds numbers smaller than about 38.

  16. Effect of antenatal dexamethasone on neonatal leukocyte count.

    PubMed

    Zachman, R D; Bauer, C R; Boehm, J; Korones, S B; Rigatto, H; Rao, A V

    1988-01-01

    The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups. PMID:3057139

  17. Dendritic Cells Induce a Subpopulation of IL-12Rβ2-Expressing Treg that Specifically Consumes IL-12 to Control Th1 Responses

    PubMed Central

    Sela, Uri; Park, Chae Gyu; Park, Andrew; Olds, Peter; Wang, Shu; Fischetti, Vincent A.

    2016-01-01

    Cytokines secreted from dendritic cells (DCs) play an important role in the regulation of T helper (Th) cell differentiation and activation into effector cells. Therefore, controlling cytokine secretion from DCs may potentially regulate Th differentiation/activation. DCs also induce de-novo generation of regulatory T cells (Treg) that modulate the immune response. In the current study we used the mixed leukocyte reaction (MLR) to investigate the effect of allospecific Treg on IL-12, TNFα and IL-6 secretion by DCs. Treg cells were found to markedly down-regulate IL-12 secretion from DCs following stimulation with TLR7/8 agonist. This down-regulation of IL-12 was neither due to a direct suppression of its production by the DCs nor a result of marked DC death. We found that IL-12 was rather actively consumed by Treg cells. IL-12 consumption was mediated by a subpopulation of IL-12Rβ2-expressing Treg cells and was dependent on MHC class-II expressed on dendritic cells. Furthermore, IL-12 consumption by Tregs increased their suppressive effect on T cell proliferation and Th1 activation. These results provide a new pathway of Th1 response regulation where IL-12 secreted by DCs is consumed by a sub-population of IL-12Rβ2-expressing Treg cells. Consumption of IL-12 by Tregs not only reduces the availability of IL-12 to Th effector cells but also enhances the Treg immunosuppressive effect. This DC-induced IL-12Rβ2-expressing Treg subpopulation may have a therapeutic advantage in suppressing Th1 mediated autoimmunity. PMID:26745371

  18. Primary activity standardization of ⁹⁹Tc by three different absolute methods.

    PubMed

    da Cruz, Paulo A L; da Silva, Carlos J; Moreira, Denise S; Iwahara, Akira; Tauhata, Luiz; Lopes, Ricardo T

    2014-05-01

    The activity concentration of a solution of (99)Tc was absolutely determined by liquid scintillation measurements based on the triple-to double-coincidence ratio method (TDCR) and compared with the results given by 4πβ(LS)-γ(NaI) live-timed anticoincidence (with extending dead-time) and classical 4πβ(PC)-γ(NaI) coincidence counting systems based on using (60)Co as the efficiency-tracing radionuclide. The results of anticoincidence and coincidence counting are, respectively, 0.18% and 0.66% higher than the result from TDCR measurements, but they are consistent within uncertainties. PMID:24365467

  19. Oncoprotein mdig contributes to silica-induced pulmonary fibrosis by altering balance between Th17 and Treg T cells

    PubMed Central

    Sun, Jiaying; Zhang, Yadong; Lu, Yongju; Battelli, Lori; Porter, Dale W.; Chen, Fei

    2015-01-01

    Mineral dust-induced gene (mdig, also named Mina53) was first identified from alveolar macrophages of the coal miners with chronic lung inflammation or fibrosis, but how this gene is involved in lung diseases is poorly understood. Here we show that heterozygotic knockout of mdig (mdig+/−) ameliorates silica-induced lung fibrosis by altering the balance between Th17 cells and Treg cells. Relative to the wild type (WT) mice, infiltration of the macrophages and Th17 cells was reduced in lungs from silica-exposed mdig+/− mice. In contrast, an increased infiltration of the T regulatory (Treg) cells to the lung intestitium was observed in the mdig+/− mice treated with silica. Both the number of Th17 cells in the lung lymph nodes and the level of IL-17 in the bronchoalveolar lavage fluids were decreased in the mdig+/− mice in response to silica. Thus, these results suggest that mdig may contribute to silica-induced lung fibrosis by altering the balance between Th17 and Treg cells. Genetic deficiency of mdig impairs Th17 cell infiltration and function, but favors infiltration of the Treg cells, the immune suppressive T cells that are able to limit the inflammatory responses by repressing the Th17 cells and macrophages. PMID:25669985

  20. Absolute magnitudes of trans-neptunian objects

    NASA Astrophysics Data System (ADS)

    Duffard, R.; Alvarez-candal, A.; Pinilla-Alonso, N.; Ortiz, J. L.; Morales, N.; Santos-Sanz, P.; Thirouin, A.

    2015-10-01

    Accurate measurements of diameters of trans- Neptunian objects are extremely complicated to obtain. Radiomatric techniques applied to thermal measurements can provide good results, but precise absolute magnitudes are needed to constrain diameters and albedos. Our objective is to measure accurate absolute magnitudes for a sample of trans- Neptunian objects, many of which have been observed, and modelled, by the "TNOs are cool" team, one of Herschel Space Observatory key projects grantes with ~ 400 hours of observing time. We observed 56 objects in filters V and R, if possible. These data, along with data available in the literature, was used to obtain phase curves and to measure absolute magnitudes by assuming a linear trend of the phase curves and considering magnitude variability due to rotational light-curve. In total we obtained 234 new magnitudes for the 56 objects, 6 of them with no reported previous measurements. Including the data from the literature we report a total of 109 absolute magnitudes.

  1. A New Gimmick for Assigning Absolute Configuration.

    ERIC Educational Resources Information Center

    Ayorinde, F. O.

    1983-01-01

    A five-step procedure is provided to help students in making the assignment absolute configuration less bothersome. Examples for both single (2-butanol) and multi-chiral carbon (3-chloro-2-butanol) molecules are included. (JN)

  2. The Simplicity Argument and Absolute Morality

    ERIC Educational Resources Information Center

    Mijuskovic, Ben

    1975-01-01

    In this paper the author has maintained that there is a similarity of thought to be found in the writings of Cudworth, Emerson, and Husserl in his investigation of an absolute system of morality. (Author/RK)

  3. Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

    PubMed Central

    Yang, Xue

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE. PMID:27597882

  4. Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

    PubMed Central

    Yang, Xue

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE.

  5. Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus.

    PubMed

    Yang, Ji; Yang, Xue; Zou, Hejian; Li, Ming

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE. PMID:27597882

  6. TH17, TH22 and TReg Cells Are Enriched in the Healthy Human Cecum

    PubMed Central

    Wolff, Martin J.; Leung, Jacqueline M.; Davenport, Michael; Poles, Michael A.; Cho, Ilseung; Loke, P'ng

    2012-01-01

    There is increasing evidence that dysregulation of CD4+ T cell populations leads to intestinal inflammation, but the regional distribution of these populations throughout the intestinal tract in healthy individuals remains unclear. Here, we show that TH17, TH22 and TReg cells are enriched in the healthy human cecum compared to the terminal ileum and sigmoid colon, whereas TH1 and TH2 cells do not significantly vary by location. Transcriptional profiling analysis of paired pinch biopsies from different regions of the intestine identified significant differences in the metabolic state of the terminal ileum, cecum, and sigmoid colon. An increased proportion of TH17 cells was positively associated with expression of resistin (RETN) and negatively associated with expression of trefoil factor 1 (TFF1). These results suggest that CD4+ T helper cells that are important in maintaining mucosal barrier function may be enriched in the cecum as a result of metabolic differences of the surrounding microenvironment. PMID:22829946

  7. Rapamycin ameliorates CCl4-induced liver fibrosis in mice through reciprocal regulation of the Th17/Treg cell balance

    PubMed Central

    Gu, Lei; Deng, Wen-Sheng; Sun, Xiao-Fei; Zhou, Hong; Xu, Qing

    2016-01-01

    Previous investigations have suggested that the activation of Th17 cells and/or deficiency of regulatory T cells (Tregs) are involved in the pathogenesis of liver fibrosis. The aim of the present study was to investigate the effect of rapamycin on immune responses in a carbon tetrachloride (CCl4)-induced murine liver fibrosis model. Liver fibrosis was induced by intraperitoneal administration with CCl4. Following injection of CCl4, the mice were treated intraperitoneally with rapamycin (1.25 mg/kg/day) for 8 weeks. Hematoxylin and eosin staining and Masson's trichrome staining were used for histological examination. The protein levels of forkhead/winged helix transcription factor P3, retinoic-acid-related orphan receptor (ROR)-γt in liver tissue were determined by western blotting, the frequency of Th17 and Treg cells in the liver was evaluated by flow cytometry, and a suppression assay was measured by incorporating [3H]-thymidine. In addition, to explore the effect of Tregs expanded with rapamycin on hepatic stellate cells (HSC), HSCs were co-cultured with Tregs from rapamycin or phosphate-buffered saline-treated mice. It was found that rapamycin treatment led to a significant reduction in the number of Th17 cells and in the expression levels of ROR-γt in the liver tissues. Simultaneously, the results of the present study showed a significant increase in the frequency of Tregs and a marked enhancement in the expression of forkhead/winged helix transcription factor P3 in the rapamycin-treated mice. Furthermore, the Tregs in rapamycin-treated mice had significantly higher suppressive effects, compared with the cells from mice treated with phospphate-buffered saline. Consequently, rapamycin treatment prevented the development of CCl4-induced hepatic fibrosis, which was shown by its histological appearances. These results suggested that the immunosuppressive effect of rapamycin on liver fibrosis was associated with the suppression of hepatic fibrogenesis and

  8. Shape analysis of counts maps

    NASA Astrophysics Data System (ADS)

    Klatt, M. A.; Göring, D.; Stegmann, C.; Mecke, K.

    2012-12-01

    A novel approach for source detection via structural deviations from the typical features of a random background counts map is presented. Minkowski functionals, powerful tools from integral geometry, quantify the shape of level sets of a counts map. Compared to standard techniques, which use the total number of counts only, additional morphometric information is incorporated without the need for any prior knowledge about the source. Minkowski sky maps quantify local structural deviations; they localize and visualize potential sources.

  9. Naive Treg-like CCR7(+) mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma.

    PubMed

    Shi, Jie-Yi; Duan, Meng; Sun, Qi-Man; Yang, Liuxiao; Wang, Zhi-Chao; Mynbaev, Ospan A; He, Yi-Feng; Wang, Ling-Yan; Zhou, Jian; Tang, Qi-Qun; Cao, Ya; Fan, Jia; Wang, Xiao-Ying; Gao, Qiang

    2016-07-01

    Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P < 0.001, r = 0.391). High density of CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P < 0.05). Survival analyses revealed that increased number of CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1. PMID:26813566

  10. Renal allograft rejection: examination of delayed differentiation of Treg and Th17 effector T cells.

    PubMed

    Pekalski, Marcin; Jenkinson, Sarah E; Willet, Joseph D P; Poyner, Elizabeth F M; Alhamidi, Abdulaziz H; Robertson, Helen; Ali, Simi; Kirby, John A

    2013-03-01

    Antigen presentation after kidney transplantation occurs in lymphoid tissues remote from the allograft, with activated T cells then migrating towards the graft. This study examined the possibility that these activated T cells can differentiate to acquire Th17 or Treg phenotypes after a time consistent with their arrival within renal allograft tissues. An immunocytochemical study was performed to demonstrate the response to intragraft TGF-β and the phenotype of lymphoid cells within rejecting human renal allograft tissue. A series of in vitro experiments was then performed to determine the potential to induce these phenotypes by addition of appropriate cytokines 3days after initial T cell activation. During renal allograft rejection there was a strong response to TGF-β, and both FOXP3 and IL-17A were expressed by separate lymphoid cells in the graft infiltrate. FOXP3 could be induced to high levels by the addition of TGF-β1 3days after the initiation of allogeneic mixed leukocyte culture. This Treg marker was enriched in the sub-population of T cells expressing the cell-surface αE(CD103)β7 integrin. The RORγt transcription factor and IL-17A were induced 3days after T cell activation by the addition of TGF-β1, IL-1β, IL-6 and IL-23; many of these Th17 cells also co-expressed CD103. T cells can develop an effector phenotype following cytokine stimulation 3days after initial activation. This suggests that the intragraft T cell phenotype may be indicative of the prevailing cytokine microenvironment.

  11. A CB2-Selective Cannabinoid Suppresses T-cell Activities and Increases Tregs and IL-10

    PubMed Central

    Robinson, Rebecca H.; Meissler, Joseph J.; Fan, Xiaoxuan; Yu, Daohai; Adler, Martin W.; Eisenstein, Toby K.

    2015-01-01

    We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the active nuclear forms of the transcription factors NF-κB and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene expression profile of purified T-cells from MLR cultures generated using a PCR T-cell activation array showed that O-1966 decreased mRNA expression of CD40 ligand and CyclinD3, and increased mRNA expression of Src-like-adaptor 2 (SLA2), Suppressor of Cytokine Signaling 5 (SOCS5), and IL-10. The increase in IL-10 was confirmed by measuring IL-10 protein levels in MLR culture supernatants. Further, an increase in the percentage of regulatory T-cells (Tregs) was observed in MLR cultures. Pretreatment with anti-IL-10 resulted in a partial reversal of the inhibition of proliferation and blocked the increase of Tregs. Additionally, O-1966 treatment caused a dose-related decrease in the expression of CD4 in MLR cultures from wild-type, but not CB2R k/o, mice. These data support the potential of CB2-selective agonists as useful therapeutic agents to prolong graft survival in transplant patients, and strengthens their potential as a new class of immunosuppressive agents with broader applicability. PMID:25980325

  12. Making environmental DNA count.

    PubMed

    Kelly, Ryan P

    2016-01-01

    The arc of reception for a new technology or method--like the reception of new information itself--can pass through predictable stages, with audiences' responses evolving from 'I don't believe it', through 'well, maybe' to 'yes, everyone knows that' to, finally, 'old news'. The idea that one can sample a volume of water, sequence DNA out of it, and report what species are living nearby has experienced roughly this series of responses among biologists, beginning with the microbial biologists who developed genetic techniques to reveal the unseen microbiome. 'Macrobial' biologists and ecologists--those accustomed to dealing with species they can see and count--have been slower to adopt such molecular survey techniques, in part because of the uncertain relationship between the number of recovered DNA sequences and the abundance of whole organisms in the sampled environment. In this issue of Molecular Ecology Resources, Evans et al. (2015) quantify this relationship for a suite of nine vertebrate species consisting of eight fish and one amphibian. Having detected all of the species present with a molecular toolbox of six primer sets, they consistently find DNA abundances are associated with species' biomasses. The strength and slope of this association vary for each species and each primer set--further evidence that there is no universal parameter linking recovered DNA to species abundance--but Evans and colleagues take a significant step towards being able to answer the next question audiences tend to ask: 'Yes, but how many are there?' PMID:26768195

  13. Making environmental DNA count.

    PubMed

    Kelly, Ryan P

    2016-01-01

    The arc of reception for a new technology or method--like the reception of new information itself--can pass through predictable stages, with audiences' responses evolving from 'I don't believe it', through 'well, maybe' to 'yes, everyone knows that' to, finally, 'old news'. The idea that one can sample a volume of water, sequence DNA out of it, and report what species are living nearby has experienced roughly this series of responses among biologists, beginning with the microbial biologists who developed genetic techniques to reveal the unseen microbiome. 'Macrobial' biologists and ecologists--those accustomed to dealing with species they can see and count--have been slower to adopt such molecular survey techniques, in part because of the uncertain relationship between the number of recovered DNA sequences and the abundance of whole organisms in the sampled environment. In this issue of Molecular Ecology Resources, Evans et al. (2015) quantify this relationship for a suite of nine vertebrate species consisting of eight fish and one amphibian. Having detected all of the species present with a molecular toolbox of six primer sets, they consistently find DNA abundances are associated with species' biomasses. The strength and slope of this association vary for each species and each primer set--further evidence that there is no universal parameter linking recovered DNA to species abundance--but Evans and colleagues take a significant step towards being able to answer the next question audiences tend to ask: 'Yes, but how many are there?'

  14. Equilibrium of Treg/Th17 cells of peripheral blood in syphilitic patients with sero-resistance

    PubMed Central

    ZHAO, JIANBIN; MA, JIE; ZHANG, XIAOYAN; LI, QING; YANG, XUEPING

    2016-01-01

    The aim of the present study was to examine changes of cellular homeostasis in regulatory T (Treg) and T helper 17 (Th17) cells by detecting the proportion of Treg and Th17 cells of peripheral blood, as well as the expression of specific transcription factors in these two types of cells, in syphilitic patients with sero-resistance. A total of 49 subjects were enrolled in the study and divided into two groups, comprising 26 cases of sero-resistant syphilitic patients in the experimental group, and 23 cases of healthy donors in the normal control group. Flow cytometry was applied to examine the proportion of Treg and Th17 cells, as well as the quantitative expression of relevant specific transcription factors [forkhead box P3 (Foxp3) and retinoic acid-related orphan receptor γt (ROR-γt)] in the two groups. A correlation analysis was subsequently performed. The results showed that in syphilitic patients with sero-resistance, the proportion of peripheral blood Treg cells was obviously higher than that of the normal control group (p<0.01) and the proportion of Th17 cells was significantly lower than that of the normal control group (p<0.01). In addition, the expression of transcription factor Foxp3 in CD4+ T cells was higher than that of the normal control group, while the expression of ROR-γt was lower than that of the normal control (p<0.05). The expression of Foxp3 and ROR-γt in peripheral blood CD4+ T cells had a negative correlation (r=−0.481, p<0.01). In conclusion, the peripheral blood of syphilitic patients with sero-resistance may have abnormalities in Treg/Th17 cellular balance. PMID:27284313

  15. Compton suppression gamma-counting: The effect of count rate

    USGS Publications Warehouse

    Millard, H.T.

    1984-01-01

    Past research has shown that anti-coincidence shielded Ge(Li) spectrometers enhanced the signal-to-background ratios for gamma-photopeaks, which are situated on high Compton backgrounds. Ordinarily, an anti- or non-coincidence spectrum (A) and a coincidence spectrum (C) are collected simultaneously with these systems. To be useful in neutron activation analysis (NAA), the fractions of the photopeak counts routed to the two spectra must be constant from sample to sample to variations must be corrected quantitatively. Most Compton suppression counting has been done at low count rate, but in NAA applications, count rates may be much higher. To operate over the wider dynamic range, the effect of count rate on the ratio of the photopeak counts in the two spectra (A/C) was studied. It was found that as the count rate increases, A/C decreases for gammas not coincident with other gammas from the same decay. For gammas coincident with other gammas, A/C increases to a maximum and then decreases. These results suggest that calibration curves are required to correct photopeak areas so quantitative data can be obtained at higher count rates. ?? 1984.

  16. Energy dispersive X-ray analysis on an absolute scale in scanning transmission electron microscopy.

    PubMed

    Chen, Z; D'Alfonso, A J; Weyland, M; Taplin, D J; Allen, L J; Findlay, S D

    2015-10-01

    We demonstrate absolute scale agreement between the number of X-ray counts in energy dispersive X-ray spectroscopy using an atomic-scale coherent electron probe and first-principles simulations. Scan-averaged spectra were collected across a range of thicknesses with precisely determined and controlled microscope parameters. Ionization cross-sections were calculated using the quantum excitation of phonons model, incorporating dynamical (multiple) electron scattering, which is seen to be important even for very thin specimens.

  17. NAD+ regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4+ CD25+ Foxp3+ T cells independent

    PubMed Central

    Elkhal, Abdallah; Rodriguez Cetina Biefer, Hector; Heinbokel, Timm; Uehara, Hirofumi; Quante, Markus; Seyda, Midas; Schuitenmaker, Jeroen M.; Krenzien, Felix; Camacho, Virginia; de la Fuente, Miguel A.; Ghiran, Ionita; Tullius, Stefan G.

    2016-01-01

    CD4+ CD25+ Foxp3+ Tregs have been shown to play a central role in immune homeostasis while preventing from fatal inflammatory responses, while Th17 cells have traditionally been recognized as pro-inflammatory mediators implicated in a myriad of diseases. Studies have shown the potential of Tregs to convert into Th17 cells, and Th17 cells into Tregs. Increasing evidence have pointed out CD25 as a key molecule during this transdifferentiation process, however molecules that allow such development remain unknown. Here, we investigated the impact of NAD+ on the fate of CD4+ CD25+ Foxp3+ Tregs in-depth, dissected their transcriptional signature profile and explored mechanisms underlying their conversion into IL-17A producing cells. Our results demonstrate that NAD+ promotes Treg conversion into Th17 cells in vitro and in vivo via CD25 cell surface marker. Despite the reduced number of Tregs, known to promote homeostasis, and an increased number of pro-inflammatory Th17 cells, NAD+ was able to promote an impressive allograft survival through a robust systemic IL-10 production that was CD4+ CD25+ Foxp3+ independent. Collectively, our study unravels a novel immunoregulatory mechanism of NAD+ that regulates Tregs fate while promoting allograft survival that may have clinical applications in alloimmunity and in a wide spectrum of inflammatory conditions. PMID:26928119

  18. Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model.

    PubMed

    Ma, Ben; Yang, Jing-Yue; Song, Wen-Jie; Ding, Rui; Zhang, Zhuo-Chao; Ji, Hong-Chen; Zhang, Xuan; Wang, Jian-Lin; Yang, Xi-Sheng; Tao, Kai-Shan; Dou, Ke-Feng; Li, Xiao

    2016-01-01

    Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30-100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used. Regulatory T cells (Tregs) can protect allografts from immune rejection, and our previous study showed that the effects of imDex were significantly associated with Tregs. Therefore, we incorporated Tregs into the treatment protocol to further reduce or avoid suppressant use. We defined the optimal exosome dose as approximately 20 μg (per treatment before, during and after transplantation) in rat liver transplantation and the antigen-specific role of Tregs in protecting liver allografts. In the co-treatment group, recipients achieved long-term survival, and tolerance was induced. Moreover, imDex amplified Tregs, which required recipient DCs and were enhanced by IL-2. Fortunately, the expanded Tregs retained their regulatory ability and donor-specificity. Thus, imDex and donor-specific Tregs can collaboratively induce graft tolerance. PMID:27640806

  19. Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model

    PubMed Central

    Ma, Ben; Yang, Jing-Yue; Song, Wen-jie; Ding, Rui; Zhang, Zhuo-chao; Ji, Hong-chen; Zhang, Xuan; Wang, Jian-lin; Yang, Xi-sheng; Tao, Kai-shan; Dou, Ke-feng; Li, Xiao

    2016-01-01

    Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30–100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used. Regulatory T cells (Tregs) can protect allografts from immune rejection, and our previous study showed that the effects of imDex were significantly associated with Tregs. Therefore, we incorporated Tregs into the treatment protocol to further reduce or avoid suppressant use. We defined the optimal exosome dose as approximately 20 μg (per treatment before, during and after transplantation) in rat liver transplantation and the antigen-specific role of Tregs in protecting liver allografts. In the co-treatment group, recipients achieved long-term survival, and tolerance was induced. Moreover, imDex amplified Tregs, which required recipient DCs and were enhanced by IL-2. Fortunately, the expanded Tregs retained their regulatory ability and donor-specificity. Thus, imDex and donor-specific Tregs can collaboratively induce graft tolerance. PMID:27640806

  20. Young Children Counting at Home

    ERIC Educational Resources Information Center

    Griffiths, Rose

    2007-01-01

    Learning to count is something that most children start to do by the time they are about two, and parents know from first-hand experience that family members play a big part in helping with this complex process. In this article, the author describes a project involving families sharing effective counting activities. The project called "Getting…

  1. Jasminum flexile flower absolute from India--a detailed comparison with three other jasmine absolutes.

    PubMed

    Braun, Norbert A; Kohlenberg, Birgit; Sim, Sherina; Meier, Manfred; Hammerschmidt, Franz-Josef

    2009-09-01

    Jasminum flexile flower absolute from the south of India and the corresponding vacuum headspace (VHS) sample of the absolute were analyzed using GC and GC-MS. Three other commercially available Indian jasmine absolutes from the species: J. sambac, J. officinale subsp. grandiflorum, and J. auriculatum and the respective VHS samples were used for comparison purposes. One hundred and twenty-one compounds were characterized in J. flexile flower absolute, with methyl linolate, benzyl salicylate, benzyl benzoate, (2E,6E)-farnesol, and benzyl acetate as the main constituents. A detailed olfactory evaluation was also performed.

  2. Hanford whole body counting manual

    SciTech Connect

    Palmer, H.E.; Brim, C.P.; Rieksts, G.A.; Rhoads, M.C.

    1987-05-01

    This document, a reprint of the Whole Body Counting Manual, was compiled to train personnel, document operation procedures, and outline quality assurance procedures. The current manual contains information on: the location, availability, and scope of services of Hanford's whole body counting facilities; the administrative aspect of the whole body counting operation; Hanford's whole body counting facilities; the step-by-step procedure involved in the different types of in vivo measurements; the detectors, preamplifiers and amplifiers, and spectroscopy equipment; the quality assurance aspect of equipment calibration and recordkeeping; data processing, record storage, results verification, report preparation, count summaries, and unit cost accounting; and the topics of minimum detectable amount and measurement accuracy and precision. 12 refs., 13 tabs.

  3. The Origins of Counting Algorithms

    PubMed Central

    Cantlon, Jessica F.; Piantadosi, Steven T.; Ferrigno, Stephen; Hughes, Kelly D.; Barnard, Allison M.

    2015-01-01

    Humans’ ability to ‘count’ by verbally labeling discrete quantities is unique in animal cognition. The evolutionary origins of counting algorithms are not understood. We report that non-human primates exhibit a cognitive ability that is algorithmically and logically similar to human counting. Monkeys were given the task of choosing between two food caches. Monkeys saw one cache baited with some number of food items, one item at a time. Then, a second cache was baited with food items, one at a time. At the point when the second set approximately outnumbered the first set, monkeys spontaneously moved to choose the second set even before it was completely baited. Using a novel Bayesian analysis, we show that monkeys used an approximate counting algorithm to increment and compare quantities in sequence. This algorithm is structurally similar to formal counting in humans and thus may have been an important evolutionary precursor to human counting. PMID:25953949

  4. Universal Cosmic Absolute and Modern Science

    NASA Astrophysics Data System (ADS)

    Kostro, Ludwik

    The official Sciences, especially all natural sciences, respect in their researches the principle of methodic naturalism i.e. they consider all phenomena as entirely natural and therefore in their scientific explanations they do never adduce or cite supernatural entities and forces. The purpose of this paper is to show that Modern Science has its own self-existent, self-acting, and self-sufficient Natural All-in Being or Omni-Being i.e. the entire Nature as a Whole that justifies the scientific methodic naturalism. Since this Natural All-in Being is one and only It should be considered as the own scientifically justified Natural Absolute of Science and should be called, in my opinion, the Universal Cosmic Absolute of Modern Science. It will be also shown that the Universal Cosmic Absolute is ontologically enormously stratified and is in its ultimate i.e. in its most fundamental stratum trans-reistic and trans-personal. It means that in its basic stratum. It is neither a Thing or a Person although It contains in Itself all things and persons with all other sentient and conscious individuals as well, On the turn of the 20th century the Science has begun to look for a theory of everything, for a final theory, for a master theory. In my opinion the natural Universal Cosmic Absolute will constitute in such a theory the radical all penetrating Ultimate Basic Reality and will substitute step by step the traditional supernatural personal Absolute.

  5. Counting reticulocytes by flow cytometry: use of thiazole orange.

    PubMed

    Carter, J M; McSweeney, P A; Wakem, P J; Nemet, A M

    1989-01-01

    Thiazole orange is a new fluorescent dye which will bind to the residual RNA in the cytoplasm of reticulocytes and allow their enumeration by FACS analysis. We have evaluated the use of this dye in the routine haematology laboratory. There is an excellent correlation between manual and FACS reticulocyte counts (r = 0.98) but FACS counting showed significantly higher precision (CV = 3.1) than the manual method (CV = 11.9) for single observer, 20.8% for multiple observers). Clinical specimens showed stable reticulocyte counts for 6 h if stored at 4 degrees C allowing efficient batching of samples. There was a significant fall in reticulocyte counts stored for 24 h at both 4 degrees C and 21 degrees C. Evaluation of 78 male and 76 female blood donors by FACS analysis gave normal ranges (mean % +/- 2 SD) of 0.74 +/- 0.48 and 0.84 +/- 0.56 respectively (P less than 0.005). When corrected to absolute values there was no sex difference (36 +/- 24 x 10(9)/l). Thiazole orange is an effective stain for the automated counting of reticulocytes by FACS analysis.

  6. Automated counting of bacterial colonies by image analysis.

    PubMed

    Chiang, Pei-Ju; Tseng, Min-Jen; He, Zong-Sian; Li, Chia-Hsun

    2015-01-01

    Research on microorganisms often involves culturing as a means to determine the survival and proliferation of bacteria. The number of colonies in a culture is counted to calculate the concentration of bacteria in the original broth; however, manual counting can be time-consuming and imprecise. To save time and prevent inconsistencies, this study proposes a fully automated counting system using image processing methods. To accurately estimate the number of viable bacteria in a known volume of suspension, colonies distributing over the whole surface area of a plate, including the central and rim areas of a Petri dish are taken into account. The performance of the proposed system is compared with verified manual counts, as well as with two freely available counting software programs. Comparisons show that the proposed system is an effective method with excellent accuracy with mean value of absolute percentage error of 3.37%. A user-friendly graphical user interface is also developed and freely available for download, providing researchers in biomedicine with a more convenient instrument for the enumeration of bacterial colonies. PMID:25451456

  7. Quantum theory allows for absolute maximal contextuality

    NASA Astrophysics Data System (ADS)

    Amaral, Barbara; Cunha, Marcelo Terra; Cabello, Adán

    2015-12-01

    Contextuality is a fundamental feature of quantum theory and a necessary resource for quantum computation and communication. It is therefore important to investigate how large contextuality can be in quantum theory. Linear contextuality witnesses can be expressed as a sum S of n probabilities, and the independence number α and the Tsirelson-like number ϑ of the corresponding exclusivity graph are, respectively, the maximum of S for noncontextual theories and for the theory under consideration. A theory allows for absolute maximal contextuality if it has scenarios in which ϑ /α approaches n . Here we show that quantum theory allows for absolute maximal contextuality despite what is suggested by the examination of the quantum violations of Bell and noncontextuality inequalities considered in the past. Our proof is not constructive and does not single out explicit scenarios. Nevertheless, we identify scenarios in which quantum theory allows for almost-absolute-maximal contextuality.

  8. Absolute calibration in vivo measurement systems

    SciTech Connect

    Kruchten, D.A.; Hickman, D.P.

    1991-02-01

    Lawrence Livermore National Laboratory (LLNL) is currently investigating a new method for obtaining absolute calibration factors for radiation measurement systems used to measure internally deposited radionuclides in vivo. Absolute calibration of in vivo measurement systems will eliminate the need to generate a series of human surrogate structures (i.e., phantoms) for calibrating in vivo measurement systems. The absolute calibration of in vivo measurement systems utilizes magnetic resonance imaging (MRI) to define physiological structure, size, and composition. The MRI image provides a digitized representation of the physiological structure, which allows for any mathematical distribution of radionuclides within the body. Using Monte Carlo transport codes, the emission spectrum from the body is predicted. The in vivo measurement equipment is calibrated using the Monte Carlo code and adjusting for the intrinsic properties of the detection system. The calibration factors are verified using measurements of existing phantoms and previously obtained measurements of human volunteers. 8 refs.

  9. Stimulus probability effects in absolute identification.

    PubMed

    Kent, Christopher; Lamberts, Koen

    2016-05-01

    This study investigated the effect of stimulus presentation probability on accuracy and response times in an absolute identification task. Three schedules of presentation were used to investigate the interaction between presentation probability and stimulus position within the set. Data from individual participants indicated strong effects of presentation probability on both proportion correct and response times. The effects were moderated by the ubiquitous stimulus position effect. The accuracy and response time data were predicted by an exemplar-based model of perceptual cognition (Kent & Lamberts, 2005). The bow in discriminability was also attenuated when presentation probability for middle items was relatively high, an effect that will constrain future model development. The study provides evidence for item-specific learning in absolute identification. Implications for other theories of absolute identification are discussed. (PsycINFO Database Record

  10. Quantitative standards for absolute linguistic universals.

    PubMed

    Piantadosi, Steven T; Gibson, Edward

    2014-01-01

    Absolute linguistic universals are often justified by cross-linguistic analysis: If all observed languages exhibit a property, the property is taken to be a likely universal, perhaps specified in the cognitive or linguistic systems of language learners and users. In many cases, these patterns are then taken to motivate linguistic theory. Here, we show that cross-linguistic analysis will very rarely be able to statistically justify absolute, inviolable patterns in language. We formalize two statistical methods--frequentist and Bayesian--and show that in both it is possible to find strict linguistic universals, but that the numbers of independent languages necessary to do so is generally unachievable. This suggests that methods other than typological statistics are necessary to establish absolute properties of human language, and thus that many of the purported universals in linguistics have not received sufficient empirical justification.

  11. Absolute photoacoustic thermometry in deep tissue.

    PubMed

    Yao, Junjie; Ke, Haixin; Tai, Stephen; Zhou, Yong; Wang, Lihong V

    2013-12-15

    Photoacoustic thermography is a promising tool for temperature measurement in deep tissue. Here we propose an absolute temperature measurement method based on the dual temperature dependences of the Grüneisen parameter and the speed of sound in tissue. By taking ratiometric measurements at two adjacent temperatures, we can eliminate the factors that are temperature irrelevant but difficult to correct for in deep tissue. To validate our method, absolute temperatures of blood-filled tubes embedded ~9 mm deep in chicken tissue were measured in a biologically relevant range from 28°C to 46°C. The temperature measurement accuracy was ~0.6°C. The results suggest that our method can be potentially used for absolute temperature monitoring in deep tissue during thermotherapy.

  12. Molecular iodine absolute frequencies. Final report

    SciTech Connect

    Sansonetti, C.J.

    1990-06-25

    Fifty specified lines of {sup 127}I{sub 2} were studied by Doppler-free frequency modulation spectroscopy. For each line the classification of the molecular transition was determined, hyperfine components were identified, and one well-resolved component was selected for precise determination of its absolute frequency. In 3 cases, a nearby alternate line was selected for measurement because no well-resolved component was found for the specified line. Absolute frequency determinations were made with an estimated uncertainty of 1.1 MHz by locking a dye laser to the selected hyperfine component and measuring its wave number with a high-precision Fabry-Perot wavemeter. For each line results of the absolute measurement, the line classification, and a Doppler-free spectrum are given.

  13. The origins of counting algorithms.

    PubMed

    Cantlon, Jessica F; Piantadosi, Steven T; Ferrigno, Stephen; Hughes, Kelly D; Barnard, Allison M

    2015-06-01

    Humans' ability to count by verbally labeling discrete quantities is unique in animal cognition. The evolutionary origins of counting algorithms are not understood. We report that nonhuman primates exhibit a cognitive ability that is algorithmically and logically similar to human counting. Monkeys were given the task of choosing between two food caches. First, they saw one cache baited with some number of food items, one item at a time. Then, a second cache was baited with food items, one at a time. At the point when the second set was approximately equal to the first set, the monkeys spontaneously moved to choose the second set even before that cache was completely baited. Using a novel Bayesian analysis, we show that the monkeys used an approximate counting algorithm for comparing quantities in sequence that is incremental, iterative, and condition controlled. This proto-counting algorithm is structurally similar to formal counting in humans and thus may have been an important evolutionary precursor to human counting. PMID:25953949

  14. Absolute Stability And Hyperstability In Hilbert Space

    NASA Technical Reports Server (NTRS)

    Wen, John Ting-Yung

    1989-01-01

    Theorems on stabilities of feedback control systems proved. Paper presents recent developments regarding theorems of absolute stability and hyperstability of feedforward-and-feedback control system. Theorems applied in analysis of nonlinear, adaptive, and robust control. Extended to provide sufficient conditions for stability in system including nonlinear feedback subsystem and linear time-invariant (LTI) feedforward subsystem, state space of which is Hilbert space, and input and output spaces having finite numbers of dimensions. (In case of absolute stability, feedback subsystem memoryless and possibly time varying. For hyperstability, feedback system dynamical system.)

  15. Weirs: Counting and sampling adult salmonids in streams and rivers

    USGS Publications Warehouse

    Zimmerman, Christian E.; Zabkar, Laura M.; Johnson, David H.; Shrier, Brianna M.; O'Neal, Jennifer S.; Knutzen, John A.; Augerot, Xanthippe; O'Neal, Thomas A.; Pearsons, Todd N.

    2007-01-01

    Weirs—which function as porous barriers built across stream—have long been used to capture migrating fish in flowing waters. For example, the Netsilik peoples of northern Canada used V-shaped weirs constructed of river rocks gathered onsite to capture migrating Arctic char Salvelinus alpinus (Balikci 1970). Similarly, fences constructed of stakes and a latticework of willow branches or staves were used by Native Americans to capture migrating salmon in streams along the West Coast of North America (Stewart 1994). In modern times, weirs have also been used in terminal fisheries and to capture brood fish for use in fish culture. Weirs have been used to gather data on age structure, condition, sex ratio, spawning escapement, abundance, and migratory patterns of fish in streams. One of the critical elements of fisheries management and stock assessment of salmonids is a count of adult fish returning to spawn. Weirs are frequently used to capture or count fish to determine status and trends of populations or direct inseason management of fisheries; generally, weirs are the standard against which other techniques are measured. To evaluate fishery management actions, the number of fish escaping to spawn is often compared to river-specific target spawning requirements (O’Connell and Dempson 1995). A critical factor in these analyses is the determination of total run size (O’Connell 2003). O’Connell compared methods of run-size estimation against absolute counts from a rigid weir and concluded that, given the uncertainty of estimators, the absolute counts obtained at the weir wer significantly better than modeled estimates, which deviated as much as 50–60% from actual counts. The use of weirs is generally restricted to streams and small rivers because of construction expense, formation of navigation barriers, and the tendency of weirs to clog with debris, which can cause flooding and collapse of the structure (Hubert 1996). When feasible, however, weirs are

  16. White blood cell counting system

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The design, fabrication, and tests of a prototype white blood cell counting system for use in the Skylab IMSS are presented. The counting system consists of a sample collection subsystem, sample dilution and fluid containment subsystem, and a cell counter. Preliminary test results show the sample collection and the dilution subsystems are functional and fulfill design goals. Results for the fluid containment subsystem show the handling bags cause counting errors due to: (1) adsorption of cells to the walls of the container, and (2) inadequate cleaning of the plastic bag material before fabrication. It was recommended that another bag material be selected.

  17. Treatment with Cordyceps sinensis enriches Treg population in peripheral lymph nodes and delays type I diabetes development in NOD mice.

    PubMed

    Wang, Mei-Fen; Zhu, Qing-Hua; He, Yu-Gong

    2013-09-01

    Cordyceps sinensis is a widely used Chinese traditional herb with a long history. In China C. sinensis is usually applied in the treatment of respiratory diseases, however, the efficacy of C. sinensis still lacks experimental evidence. Type I diabetes is a multi-factor related autoimmune disease caused by cellular-mediated destruction of insulin-producing pancreatic beta cells in the islets in human. We tested C. sinensis for its ability to work as an immune modulator in NOD mice, an animal model which mimicks the progression of type I diabetes in humans and found that treatment with C. sinensis extract could slow down disease development in NOD mice. Further research also suggested that treatment with C. sinensis extract increased the frequency of Treg cells and IFN-gama producing Th1 cells in peripheral lymph nodes. However, C. sinensis has no effect on the natural Treg cell differentiation in thymus. PMID:24147346

  18. The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation.

    PubMed

    Kabat, Agnieszka M; Harrison, Oliver J; Riffelmacher, Thomas; Moghaddam, Amin E; Pearson, Claire F; Laing, Adam; Abeler-Dörner, Lucie; Forman, Simon P; Grencis, Richard K; Sattentau, Quentin; Simon, Anna Katharina; Pott, Johanna; Maloy, Kevin J

    2016-02-24

    A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) Treg cells. Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders.

  19. The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation.

    PubMed

    Kabat, Agnieszka M; Harrison, Oliver J; Riffelmacher, Thomas; Moghaddam, Amin E; Pearson, Claire F; Laing, Adam; Abeler-Dörner, Lucie; Forman, Simon P; Grencis, Richard K; Sattentau, Quentin; Simon, Anna Katharina; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) Treg cells. Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders. PMID:26910010

  20. Counting Triangles to Sum Squares

    ERIC Educational Resources Information Center

    DeMaio, Joe

    2012-01-01

    Counting complete subgraphs of three vertices in complete graphs, yields combinatorial arguments for identities for sums of squares of integers, odd integers, even integers and sums of the triangular numbers.

  1. Complete Blood Count (For Parents)

    MedlinePlus

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... Metabolic Panel (BMP) Blood Test: Hemoglobin Basic Blood Chemistry Tests Word! Complete Blood Count (CBC) Medical Tests ...

  2. Absolute Points for Multiple Assignment Problems

    ERIC Educational Resources Information Center

    Adlakha, V.; Kowalski, K.

    2006-01-01

    An algorithm is presented to solve multiple assignment problems in which a cost is incurred only when an assignment is made at a given cell. The proposed method recursively searches for single/group absolute points to identify cells that must be loaded in any optimal solution. Unlike other methods, the first solution is the optimal solution. The…

  3. Absolute partial photoionization cross sections of ozone.

    SciTech Connect

    Berkowitz, J.; Chemistry

    2008-04-01

    Despite the current concerns about ozone, absolute partial photoionization cross sections for this molecule in the vacuum ultraviolet (valence) region have been unavailable. By eclectic re-evaluation of old/new data and plausible assumptions, such cross sections have been assembled to fill this void.

  4. Stimulus Probability Effects in Absolute Identification

    ERIC Educational Resources Information Center

    Kent, Christopher; Lamberts, Koen

    2016-01-01

    This study investigated the effect of stimulus presentation probability on accuracy and response times in an absolute identification task. Three schedules of presentation were used to investigate the interaction between presentation probability and stimulus position within the set. Data from individual participants indicated strong effects of…

  5. Teaching Absolute Value Inequalities to Mature Students

    ERIC Educational Resources Information Center

    Sierpinska, Anna; Bobos, Georgeana; Pruncut, Andreea

    2011-01-01

    This paper gives an account of a teaching experiment on absolute value inequalities, whose aim was to identify characteristics of an approach that would realize the potential of the topic to develop theoretical thinking in students enrolled in prerequisite mathematics courses at a large, urban North American university. The potential is…

  6. Solving Absolute Value Equations Algebraically and Geometrically

    ERIC Educational Resources Information Center

    Shiyuan, Wei

    2005-01-01

    The way in which students can improve their comprehension by understanding the geometrical meaning of algebraic equations or solving algebraic equation geometrically is described. Students can experiment with the conditions of the absolute value equation presented, for an interesting way to form an overall understanding of the concept.

  7. Increasing Capacity: Practice Effects in Absolute Identification

    ERIC Educational Resources Information Center

    Dodds, Pennie; Donkin, Christopher; Brown, Scott D.; Heathcote, Andrew

    2011-01-01

    In most of the long history of the study of absolute identification--since Miller's (1956) seminal article--a severe limit on performance has been observed, and this limit has resisted improvement even by extensive practice. In a startling result, Rouder, Morey, Cowan, and Pfaltz (2004) found substantially improved performance with practice in the…

  8. Absolute Radiometric Calibration Of The Thematic Mapper

    NASA Astrophysics Data System (ADS)

    Slater, P. N.; Biggar, S. F.; Holm, R. G.; Jackson, R. D.; Mao, Y.; Moran, M. S.; Palmer, J. M.; Yuan, B.

    1986-11-01

    The results are presented of five in-flight absolute radiometric calibrations, made in the period July 1984 to November 1985, at White Sands, New Mexico, of the solar reflective bands of the Landsat-5 Thematic Mapper (TM) . The 23 bandcalibrations made on the five dates show a ± 2.8% RMS variation from the mean as a percentage of the mean.

  9. On Relative and Absolute Conviction in Mathematics

    ERIC Educational Resources Information Center

    Weber, Keith; Mejia-Ramos, Juan Pablo

    2015-01-01

    Conviction is a central construct in mathematics education research on justification and proof. In this paper, we claim that it is important to distinguish between absolute conviction and relative conviction. We argue that researchers in mathematics education frequently have not done so and this has lead to researchers making unwarranted claims…

  10. PEG-rIL-10 treatment decreases FoxP3(+) Tregs despite upregulation of intratumoral IDO.

    PubMed

    Chan, Ivan H; Wu, Victoria; Bilardello, Melissa; Jorgenson, Brett; Bal, Harminder; McCauley, Scott; Van Vlasselaer, Peter; Mumm, John B

    2016-07-01

    IL-10 has been classically defined as a broad-spectrum immunosuppressant and is thought to facilitate the development of regulatory CD4(+) T cells. IL-10 is believed to represent one of the major suppressive factors secreted by IDO(+)FoxP3(+)CD4(+) Tregs. Contrary to this view, we have previously reported that PEGylated recombinant IL-10 (PEG-rIL-10) treatment of mice induces potent IFNγ and CD8(+) T-cell-dependent antitumor immunity. This hypothesis is currently being tested in clinical trials and we have reported that treatment of cancer patients with PEG-rHuIL-10 results in inhibition and regression of tumor growth as well as increased serum IFNγ. We have continued to assess PEG-rIL-10's pleiotropic effects and report that treatment of tumor-bearing mice and humans with PEG-rIL-10 increases intratumoral indoleamine 2, 3-dioxygenase (IDO) in an IFNγ-dependent manner. This should result in an increase in Tregs, but paradoxically our data illustrate that PEG-rIL-10 treatment of mice reduces intratumoral FoxP3(+)CD4(+) T cells in an IDO-independent manner. Additional investigation indicates that PEG-rIL-10 inhibits TGFβ/IL-2-dependent in vitro polarization of FoxP3(+)CD4(+) Tregs and potentiates IFNγ(+)T-bet(+)CD4(+) T cells. These data suggest that rather than acting as an immunosuppressant, PEG-rIL-10 may counteract the FoxP3(+)CD4(+) Treg suppressive milieu in tumor-bearing mice and humans, thereby further facilitating PEG-rIL-10's potent antitumor immunity.

  11. PEG-rIL-10 treatment decreases FoxP3(+) Tregs despite upregulation of intratumoral IDO.

    PubMed

    Chan, Ivan H; Wu, Victoria; Bilardello, Melissa; Jorgenson, Brett; Bal, Harminder; McCauley, Scott; Van Vlasselaer, Peter; Mumm, John B

    2016-07-01

    IL-10 has been classically defined as a broad-spectrum immunosuppressant and is thought to facilitate the development of regulatory CD4(+) T cells. IL-10 is believed to represent one of the major suppressive factors secreted by IDO(+)FoxP3(+)CD4(+) Tregs. Contrary to this view, we have previously reported that PEGylated recombinant IL-10 (PEG-rIL-10) treatment of mice induces potent IFNγ and CD8(+) T-cell-dependent antitumor immunity. This hypothesis is currently being tested in clinical trials and we have reported that treatment of cancer patients with PEG-rHuIL-10 results in inhibition and regression of tumor growth as well as increased serum IFNγ. We have continued to assess PEG-rIL-10's pleiotropic effects and report that treatment of tumor-bearing mice and humans with PEG-rIL-10 increases intratumoral indoleamine 2, 3-dioxygenase (IDO) in an IFNγ-dependent manner. This should result in an increase in Tregs, but paradoxically our data illustrate that PEG-rIL-10 treatment of mice reduces intratumoral FoxP3(+)CD4(+) T cells in an IDO-independent manner. Additional investigation indicates that PEG-rIL-10 inhibits TGFβ/IL-2-dependent in vitro polarization of FoxP3(+)CD4(+) Tregs and potentiates IFNγ(+)T-bet(+)CD4(+) T cells. These data suggest that rather than acting as an immunosuppressant, PEG-rIL-10 may counteract the FoxP3(+)CD4(+) Treg suppressive milieu in tumor-bearing mice and humans, thereby further facilitating PEG-rIL-10's potent antitumor immunity. PMID:27622052

  12. Counting on Using a Number Game

    ERIC Educational Resources Information Center

    Betts, Paul

    2015-01-01

    Counting all and counting on are distinct counting strategies that can be used to compute such quantities as the total number of objects in two sets (Wright, Martland, and Stafford 2010). Given five objects and three more objects, for example, children who use counting all to determine quantity will count both collections; that is, they count…

  13. Counting individual DNA molecules by the stochastic attachment of diverse labels

    PubMed Central

    Fu, Glenn K.; Hu, Jing; Wang, Pei-Hua; Fodor, Stephen P. A.

    2011-01-01

    We implement a unique strategy for single molecule counting termed stochastic labeling, where random attachment of a diverse set of labels converts a population of identical DNA molecules into a population of distinct DNA molecules suitable for threshold detection. The conceptual framework for stochastic labeling is developed and experimentally demonstrated by determining the absolute and relative number of selected genes after stochastically labeling approximately 360,000 different fragments of the human genome. The approach does not require the physical separation of molecules and takes advantage of highly parallel methods such as microarray and sequencing technologies to simultaneously count absolute numbers of multiple targets. Stochastic labeling should be particularly useful for determining the absolute numbers of RNA or DNA molecules in single cells. PMID:21562209

  14. High avidity autoreactive CD4+ T cells induce host CTL, overcome Tregs and mediate tumor destruction

    PubMed Central

    Brandmaier, Andrew G.; Leitner, Wolfgang W.; Ha, Sung P.; Sidney, John; Restifo, Nicholas P.; Touloukian, Christopher E.

    2009-01-01

    Despite progress made over the past 25 years, existing immunotherapies have limited clinical effectiveness in patients with cancer. Immune tolerance consistently blunts the generated immune response, and the largely solitary focus on CD8+ T cell immunity has proven ineffective in the absence of CD4+ T cell help. To address these twin-tier deficiencies, we developed a translational model of melanoma immunotherapy focused on the exploitation of high avidity CD4+ T cells that become generated in germline antigen deficient mice. We had previously identified a TRP-1 specific HLA-DRB1*0401-restricted epitope. Using this epitope in conjunction with a newly described TRP-1 germline-knockout, we demonstrate that endogenous TRP-1 expression alters the functionality of the auto-reactive T cell repertoire. More importantly, we show, by using MHC-mismatched combinations, that CD4+ T cells derived from the self-antigen deficient host indirectly triggers the eradication of established B16 lung metastases. We demonstrate that the treatment effect is mediated entirely by endogenous CD8+ T cells and is not affected by the depletion of host Tregs. These findings suggest that high avidity CD4+ T cells can overcome endogenous conditions and mediate their anti-tumor effects exclusively through the elicitation of CD8+ T cell immunity. PMID:19561540

  15. mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections

    PubMed Central

    Tu, Huaijun; Guo, Wei; Wang, Shixuan; Xue, Ting; Yang, Fei; Zhang, Xiaoyan; Yang, Yazhi; Wan, Qian; Shi, Zhexin; Zhan, Xulong

    2016-01-01

    The TSC1/2 heterodimer, a key upstream regulator of the mTOR, can inhibit the activation of mTOR, which plays a critical role in immune responses after bacterial infections. Monocytes are an innate immune cell type that have been shown to be involved in bacteremia. However, how the mTOR pathway is involved in the regulation of monocytes is largely unknown. In our study, TSC1 KO mice and WT mice were infected with E. coli. When compared to WT mice, we found higher mortality, greater numbers of bacteria, decreased expression of coactivators in monocytes, increased numbers of Tregs, and decreased numbers of effector T cells in TSC1 KO mice. Monocytes obtained from TSC1 KO mice produced more ROS, IL-6, IL-10, and TGF-β and less IL-1, IFN-γ, and TNF-α. Taken together, our results suggest that the inhibited immune functioning in TSC1 KO mice is influenced by mTORC1 activation in monocytes. The reduced expression of coactivators resulted in inhibited effector T cell proliferation. mTORC1-activated monocytes are harmful during bacterial infections. Therefore, inhibiting mTORC1 signaling through rapamycin administration could rescue the harmful aspects of an overactive immune response, and this knowledge provides a new direction for clinical therapy. PMID:27746591

  16. TREG coated iron oxide nanoparticles as contrast agent for MRI in-vivo use

    NASA Astrophysics Data System (ADS)

    Gutierrez-Garcia, Eric; Hidalgo-Tobon, Silvia; Lopez, Ciro; Gonzalez-Rodriguez, Roberto; Coffer, Jeffery; De Celis Alonso, Benito; Dies Suarez, Pilar; Obregon, Manuel; Perez-Pena, Mario; Platas-Neri, Diana; Mendez-Rojas, Miguel

    2014-11-01

    Super-paramagnetic iron oxide nanoparticles (SPIONs) are of interest due to their great potential applications in diverse fields such as biomedicine. In this work we have prepared SPION nanoparticles using the polyol technique and characterized the magnetic properties of them for MRI in-vivo use. Nanoparticle preparation: All reagents were purchased from commercial sources (Sigma-Aldrich, St. Louis, USA) Iron (III) acetylacetonate, [Fe(acac)3], was used as the iron oxide precursor and thermally decomposed at high temperatures in triethyleneglycol (TREG). Nano-sized magnetite particles were prepared by an adaptation of the method proposed by Wei Cai et al[1-3]. A healthy rabbit was scanned on a clinical 1.5 T Philips MR scanner. Images were taken in 2D mode with a mFFE sequence. Relaxation time T2 was obtained from the MR images using a Matlab algorithm where the signal intensity decay was calculated at each image and then adjusted to a mono-exponential curve. Images were obtained before contrast injection, 24 hours and 36 hours following SPIONs administration. Signal decay at different Echo times for the prepared magnetic SPIONs, before and after contrast injection was measured. It was visualized a concentration of the agent contrast in brain and liver and the results were compared with images obtained from histopathology.

  17. Exploring the induction of preproinsulin-specific Foxp3+ CD4+ Treg cells that inhibit CD8+ T cell-mediated autoimmune diabetes by DNA vaccination

    PubMed Central

    Stifter, Katja; Schuster, Cornelia; Schlosser, Michael; Boehm, Bernhard Otto; Schirmbeck, Reinhold

    2016-01-01

    DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3+ CD25+ CD4+ Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8+ T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced Kb/A12-21-monospecific CD8+ T cells and autoimmune diabetes. A pCI/ppinsΔA12-21 vector (lacking the critical Kb/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3+ CD25+ Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-β expression was significantly enhanced in the Foxp3+ CD25+ Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1−/− hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76–90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8+ T cells in this diabetes model. PMID:27406624

  18. Protection of Tregs, Suppression of Th1 and Th17 Cells, and Amelioration of Experimental Allergic Encephalomyelitis by a Physically-Modified Saline

    PubMed Central

    Mondal, Susanta; Martinson, Jeffrey A.; Ghosh, Supurna; Watson, Richard; Pahan, Kalipada

    2012-01-01

    In multiple sclerosis (MS) and other autoimmune diseases, the autoreactive T cells overcome the resistance provided by the regulatory T cells (Tregs) due to a decrease in the number of Foxp3-expressing Tregs. Therefore, upregulation and/or maintenance of Tregs during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Here we have undertaken an innovative approach to upregulate Tregs and achieve immunomodulation. RNS60 is a 0.9% saline solution generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), RNS10.3 (TCP-modified saline without excess oxygen) and PNS60 (saline containing excess oxygen without TCP modification), was found to upregulate Foxp3 and enrich Tregs in MBP-primed T cells. Moreover, RNS60, but not NS, RNS10.3 and PNS60, inhibited the production of nitric oxide (NO) and the expression of iNOS in MBP-primed splenocytes. Incubation of the cells with an NO donor abrogated the RNS60-mediated upregulation of Foxp3. These results suggest that RNS60 boosts Tregs via suppression of NO production. Consistent to the suppressive activity of Tregs towards autoreactive T cells, RNS60, but not NS, RNS10.3, or PNS60, suppressed the differentiation of Th17 and Th1 cells and shifted the balance towards a Th2 response. Finally, RNS60 treatment exhibited immunomodulation and ameliorated adoptive transfer of experimental allergic encephalomyelitis, an animal model of MS, via Tregs. These results describe a novel immunomodulatory property of RNS60 and suggest its exploration for therapeutic intervention in MS and other autoimmune disorders. PMID:23284794

  19. Protection of Tregs, suppression of Th1 and Th17 cells, and amelioration of experimental allergic encephalomyelitis by a physically-modified saline.

    PubMed

    Mondal, Susanta; Martinson, Jeffrey A; Ghosh, Supurna; Watson, Richard; Pahan, Kalipada

    2012-01-01

    In multiple sclerosis (MS) and other autoimmune diseases, the autoreactive T cells overcome the resistance provided by the regulatory T cells (Tregs) due to a decrease in the number of Foxp3-expressing Tregs. Therefore, upregulation and/or maintenance of Tregs during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Here we have undertaken an innovative approach to upregulate Tregs and achieve immunomodulation. RNS60 is a 0.9% saline solution generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), RNS10.3 (TCP-modified saline without excess oxygen) and PNS60 (saline containing excess oxygen without TCP modification), was found to upregulate Foxp3 and enrich Tregs in MBP-primed T cells. Moreover, RNS60, but not NS, RNS10.3 and PNS60, inhibited the production of nitric oxide (NO) and the expression of iNOS in MBP-primed splenocytes. Incubation of the cells with an NO donor abrogated the RNS60-mediated upregulation of Foxp3. These results suggest that RNS60 boosts Tregs via suppression of NO production. Consistent to the suppressive activity of Tregs towards autoreactive T cells, RNS60, but not NS, RNS10.3, or PNS60, suppressed the differentiation of Th17 and Th1 cells and shifted the balance towards a Th2 response. Finally, RNS60 treatment exhibited immunomodulation and ameliorated adoptive transfer of experimental allergic encephalomyelitis, an animal model of MS, via Tregs. These results describe a novel immunomodulatory property of RNS60 and suggest its exploration for therapeutic intervention in MS and other autoimmune disorders.

  20. Epicutaneous immunization with DNP-BSA induces CD4+ CD25+ Treg cells that inhibit Tc1-mediated CS.

    PubMed

    Majewska-Szczepanik, Monika; Zemelka-Wiącek, Magdalena; Ptak, Włodzimierz; Wen, Li; Szczepanik, Marian

    2012-09-01

    As we have shown previously that protein antigen applied epicutaneously (EC) in mice inhibits TNP-specific Th1-mediated contact sensitivity (CS), we postulated that the maneuver of EC immunization might also suppress Tc1-dependent CS response. Here we showed that EC immunization of normal mice with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) applied on the skin in the form of a patch induces a state of subsequent unresponsiveness due to regulatory T cells (Treg) that inhibited sensitization and elicitation of effector T-cell responses. Suppression is transferable in vivo by TCRαβ(+) CD4(+) CD25(+) lymphocytes harvested from lymph nodes (LNs) of skin-patched animals. Flow cytometry revealed that EC immunization with DNP-BSA increased TCRαβ(+) CD4(+) CD25(+) FoxP3(+) lymphocytes in subcutaneous LNs, suggesting that observed suppression was mediated by Treg cells. Further, in vitro experiments showed that EC immunization with DNP-BSA prior to 1-fluoro-2,4-dinitrobenzen sensitization suppressed LN cell proliferation and inhibited production of TNF-α, IL-12 and IFN-γ. Using a transwell system or anti-CTLA-4 mAb, we found that EC induced suppression required direct Treg-effector cell contact and is CTLA-4-dependent.

  1. Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

    PubMed Central

    Dai, Wujing; Liu, Fangwei; Li, Chao; Lu, Yiping; Lu, Xiaowei; Du, Sitong; Chen, Ying; Weng, Dong; Chen, Jie

    2016-01-01

    CD4+ T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+ T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+ T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs). Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis. PMID:27069316

  2. Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development.

    PubMed

    Ulges, Alexander; Witsch, Esther J; Pramanik, Gautam; Klein, Matthias; Birkner, Katharina; Bühler, Ulrike; Wasser, Beatrice; Luessi, Felix; Stergiou, Natascha; Dietzen, Sarah; Brühl, Till-Julius; Bohn, Toszka; Bündgen, Georg; Kunz, Horst; Waisman, Ari; Schild, Hansjörg; Schmitt, Edgar; Zipp, Frauke; Bopp, Tobias

    2016-09-01

    T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases. However, the molecular mechanisms controlling this balance are still unclear. Here, we report that pharmacological inhibition as well as genetic ablation of the protein kinase CK2 (CK2) ameliorates experimental autoimmune encephalomyelitis (EAE) severity and relapse incidence. Furthermore, CK2 inhibition or genetic ablation prevents TH17 cell development and promotes the generation of Treg cells. Molecularly, inhibition of CK2 leads to reduced STAT3 phosphorylation and strongly attenuated expression of the IL-23 receptor, IL-17, and GM-CSF. Thus, these results identify CK2 as a nodal point in TH17 cell development and suggest this kinase as a potential therapeutic target to treat TH17 cell-driven autoimmune responses. PMID:27555590

  3. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3+ Treg cell function in the intestine

    PubMed Central

    Harrison, OJ; Srinivasan, N; Pott, J; Schiering, C; Krausgruber, T; Ilott, NE; Maloy, KJ

    2015-01-01

    Elevated levels of interleukin-18 (IL-18) are found in many chronic inflammatory disorders, including inflammatory bowel disease (IBD), and polymorphisms in the IL18R1-IL18RAP locus are associated with IBD susceptibility. IL-18 is an IL-1 family cytokine that has been proposed to promote barrier function in the intestine, but the effects of IL-18 on intestinal CD4+ T cells are poorly understood. Here, we demonstrate that IL-18R1 expression is enhanced on both effector and regulatory CD4+ T cells in the intestinal lamina propria, with Th17 cells exhibiting particularly high levels. We further show that, during steady state, intestinal epithelial cells (IEC) constitutively secrete IL-18 that acts directly on IL-18R1-expressing CD4+ T cells to limit colonic Th17 cell differentiation, in part by antagonizing IL-1R1-signalling. In addition, although IL-18R1 is not required for colonic Foxp3+ Treg cell differentiation, we found that IL-18R1 signaling was critical for Foxp3+ Treg cell mediated control of intestinal inflammation, where it promoted expression of key Treg effector molecules. Thus, IL-18 is a key epithelial-derived cytokine that differentially regulates distinct subsets of intestinal CD4+ T cells during both homeostatic and inflammatory conditions, a finding with potential implications for treatment of chronic inflammatory disorders. PMID:25736457

  4. Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development.

    PubMed

    Ulges, Alexander; Witsch, Esther J; Pramanik, Gautam; Klein, Matthias; Birkner, Katharina; Bühler, Ulrike; Wasser, Beatrice; Luessi, Felix; Stergiou, Natascha; Dietzen, Sarah; Brühl, Till-Julius; Bohn, Toszka; Bündgen, Georg; Kunz, Horst; Waisman, Ari; Schild, Hansjörg; Schmitt, Edgar; Zipp, Frauke; Bopp, Tobias

    2016-09-01

    T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases. However, the molecular mechanisms controlling this balance are still unclear. Here, we report that pharmacological inhibition as well as genetic ablation of the protein kinase CK2 (CK2) ameliorates experimental autoimmune encephalomyelitis (EAE) severity and relapse incidence. Furthermore, CK2 inhibition or genetic ablation prevents TH17 cell development and promotes the generation of Treg cells. Molecularly, inhibition of CK2 leads to reduced STAT3 phosphorylation and strongly attenuated expression of the IL-23 receptor, IL-17, and GM-CSF. Thus, these results identify CK2 as a nodal point in TH17 cell development and suggest this kinase as a potential therapeutic target to treat TH17 cell-driven autoimmune responses.

  5. Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion.

    PubMed

    Zoso, Alessia; Mazza, Emilia M C; Bicciato, Silvio; Mandruzzato, Susanna; Bronte, Vincenzo; Serafini, Paolo; Inverardi, Luca

    2014-11-01

    By restraining T-cell activation and promoting Treg-cell expansion, myeloid-derived suppressor cells (MDSCs) and tolerogenic DCs can control self-reactive and antigraft effector T cells in autoimmunity and transplantation. Their therapeutic use and characterization, however, is limited by their scarce availability in the peripheral blood of tumor-free donors. In the present study, we describe and characterize a novel population of human myeloid suppressor cells, named fibrocytic MDSC, which are differentiated from umbilical cord blood precursors by 4-day culture with FDA-approved cytokines (recombinant human-GM-CSF and recombinant human-G-CSF). This MDSC subset, characterized by the expression of MDSC-, DC-, and fibrocyte-associated markers, promotes Treg-cell expansion and induces normoglycemia in a xenogeneic mouse model of Type 1 diabetes. In order to exert their protolerogenic function, fibrocytic MDSCs require direct contact with activated T cells, which leads to the production and secretion of IDO. This new myeloid subset may have an important role in the in vitro and in vivo production of Treg cells for the treatment of autoimmune diseases, and in either the prevention or control of allograft rejection.

  6. Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice

    PubMed Central

    Woller, Norman; Knocke, Sarah; Mundt, Bettina; Gürlevik, Engin; Strüver, Nina; Kloos, Arnold; Boozari, Bita; Schache, Peter; Manns, Michael P.; Malek, Nisar P.; Sparwasser, Tim; Zender, Lars; Wirth, Thomas C.; Kubicka, Stefan; Kühnel, Florian

    2011-01-01

    Vaccination using DCs pulsed with tumor lysates or specific tumor-associated peptides has so far yielded limited clinical success for cancer treatment, due mainly to the low immunogenicity of tumor-associated antigens. In this study, we have identified intratumoral virus-induced inflammation as a precondition for effective antitumor DC vaccination in mice. Administration of a tumor-targeted DC vaccine during ongoing virus-induced tumor inflammation, a regimen referred to as oncolysis-assisted DC vaccination (ODC), elicited potent antitumoral CD8+ T cell responses. This potent effect was not replicated by TLR activation outside the context of viral infection. ODC-elicited immune responses mediated marked tumor regression and successful eradication of preestablished lung colonies, an essential prerequisite for potentially treating metastatic cancers. Unexpectedly, depletion of Tregs during ODC did not enhance therapeutic efficacy; rather, it abrogated antitumor cytotoxicity. This phenomenon could be attributed to a compensatory induction of myeloid-derived suppressor cells in Treg-depleted and thus vigorously inflamed tumors, which prevented ODC-mediated immune responses. Consequently, Tregs are not only general suppressors of immune responses, but are essential for the therapeutic success of multimodal and temporally fine-adjusted vaccination strategies. Our results highlight tumor-targeting, replication-competent viruses as attractive tools for eliciting effective antitumor responses upon DC vaccination. PMID:21646722

  7. PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs

    PubMed Central

    Lee, Seung Hoon; Park, Jin-Sil; Byun, Jae-Kyung; Jhun, JooYeon; Jung, KyungAh; Seo, Hyeon-Beom; Moon, Young-Mee; Kim, Ho-Youn; Park, Sung-Hwan; Cho, Mi-La

    2016-01-01

    PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy. PMID:27708408

  8. TGF-β/BAMBI pathway dysfunction contributes to peripheral Th17/Treg imbalance in chronic obstructive pulmonary disease

    PubMed Central

    Zhang, Jian-Chu; Chen, Gang; Chen, Long; Meng, Zhao-Ji; Xiong, Xian-Zhi; Liu, Hong-Ju; Jin, Yang; Tao, Xiao-Nan; Wu, Jiang-Hua; Sun, Sheng-Wen

    2016-01-01

    BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor β (TGF-β) signaling. Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated. In this study, we investigated whether TGF-β/BAMBI pathway is associated with COPD. Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients. Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4+ T cells respectively), were observed in COPD compared with HC and HS. BAMBI expression was first observed on human CD4+ T cells, with a typical membrane-bound pattern. The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-β1 levels and Th17/Treg ratio. Together, an impaired TGF-β/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD. PMID:27549738

  9. Low expression of CD39(+) /CD45RA(+) on regulatory T cells (Treg ) cells in type 1 diabetic children in contrast to high expression of CD101(+) /CD129(+) on Treg cells in children with coeliac disease.

    PubMed

    Åkesson, K; Tompa, A; Rydén, A; Faresjö, M

    2015-04-01

    Type 1 diabetes (T1D) and coeliac disease are both characterized by an autoimmune feature. As T1D and coeliac disease share the same risk genes, patients risk subsequently developing the other disease. This study aimed to investigate the expression of T helper (Th), T cytotoxic (Tc) and regulatory T cells (Treg ) in T1D and/or coeliac disease children in comparison to healthy children. Subgroups of T cells (Th : CD4(+) or Tc : CD8(+) ); naive (CD27(+) CD28(+) CD45RA(+) CCR7(+) ), central memory (CD27(+) CD28(+) CD45RA(-) CCR7(+) ), effector memory (early differentiated; CD27(+) CD28(+) CD45RA(-) CCR7(-) and late differentiated; CD27(-) CD28(-) CD45RA(-) CCR7(-) ), terminally differentiated effector cells (TEMRA; CD27(-) CD28(-) CD45RA(+) CCR7(-) ) and Treg (CD4(+) CD25(+) FOXP3(+) CD127(-) ) cells, and their expression of CD39, CD45RA, CD101 and CD129, were studied by flow cytometry in T1D and/or coeliac disease children or without any of these diseases (reference group). Children diagnosed with both T1D and coeliac disease showed a higher percentage of TEMRA CD4(+) cells (P < 0·05), but lower percentages of both early and late effector memory CD8(+) cells (P < 0·05) compared to references. Children with exclusively T1D had lower median fluorescence intensity (MFI) of forkhead box protein 3 (FoxP3) (P < 0·05) and also a lower percentage of CD39(+) and CD45RA(+) within the Treg population (CD4(+) CD25(+) FOXP3(+) CD127(-) ) (P < 0·05). Children with exclusively coeliac disease had a higher MFI of CD101 (P < 0·01), as well as a higher percentage of CD129(+) (P < 0·05), in the CD4(+) CD25(hi) lymphocyte population, compared to references. In conclusion, children with combined T1D and coeliac disease have a higher percentage of differentiated CD4(+) cells compared to CD8(+) cells. T1D children show signs of low CD39(+) /CD45RA(+) Treg cells that may indicate loss of suppressive function. Conversely, children with coeliac disease

  10. Measurement of the Neutron Lifetime by Counting Trapped Protons

    PubMed Central

    Wietfeldt, F. E.; Dewey, M. S.; Gilliam, D. M.; Nico, J. S.; Fei, X.; Snow, W. M.; Greene, G. L.; Pauwels, J.; Eykens, R.; Lamberty, A.; Van Gestel, J.

    2005-01-01

    We measured the neutron decay lifetime by counting in-beam neutron decay recoil protons trapped in a quasi-Penning trap. The absolute neutron beam fluence was measured by capture in a thin 6LiF foil detector with known efficiency. The combination of these measurements gives the neutron lifetime: τn = (886.8 ± 1.2 ± 3.2) s, where the first (second) uncertainty is statistical (systematic) in nature. This is the most precise neutron lifetime determination to date using an in-beam method. PMID:27308145

  11. High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas

    PubMed Central

    Lukesova, E.; Boucek, J.; Rotnaglova, E.; Salakova, M.; Koslabova, E.; Grega, M.; Eckschlager, T.; Rihova, B.; Prochazka, B.; Klozar, J.; Tachezy, R.

    2014-01-01

    Background. Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and Methods. Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results. Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion. Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence. PMID:24864233

  12. Combined Use of Absolute and Differential Seismic Arrival Time Data to Improve Absolute Event Location

    NASA Astrophysics Data System (ADS)

    Myers, S.; Johannesson, G.

    2012-12-01

    Arrival time measurements based on waveform cross correlation are becoming more common as advanced signal processing methods are applied to seismic data archives and real-time data streams. Waveform correlation can precisely measure the time difference between the arrival of two phases, and differential time data can be used to constrain relative location of events. Absolute locations are needed for many applications, which generally requires the use of absolute time data. Current methods for measuring absolute time data are approximately two orders of magnitude less precise than differential time measurements. To exploit the strengths of both absolute and differential time data, we extend our multiple-event location method Bayesloc, which previously used absolute time data only, to include the use of differential time measurements that are based on waveform cross correlation. Fundamentally, Bayesloc is a formulation of the joint probability over all parameters comprising the multiple event location system. The Markov-Chain Monte Carlo method is used to sample from the joint probability distribution given arrival data sets. The differential time component of Bayesloc includes scaling a stochastic estimate of differential time measurement precision based the waveform correlation coefficient for each datum. For a regional-distance synthetic data set with absolute and differential time measurement error of 0.25 seconds and 0.01 second, respectively, epicenter location accuracy is improved from and average of 1.05 km when solely absolute time data are used to 0.28 km when absolute and differential time data are used jointly (73% improvement). The improvement in absolute location accuracy is the result of conditionally limiting absolute location probability regions based on the precise relative position with respect to neighboring events. Bayesloc estimates of data precision are found to be accurate for the synthetic test, with absolute and differential time measurement

  13. Standardization of 241Am by digital coincidence counting, liquid scintillation counting and defined solid angle counting.

    PubMed

    Balpardo, C; Capoulat, M E; Rodrigues, D; Arenillas, P

    2010-01-01

    The nuclide (241)Am decays by alpha emission to (237)Np. Most of the decays (84.6%) populate the excited level of (237)Np with energy of 59.54 keV. Digital coincidence counting was applied to standardize a solution of (241)Am by alpha-gamma coincidence counting with efficiency extrapolation. Electronic discrimination was implemented with a pressurized proportional counter and the results were compared with two other independent techniques: Liquid scintillation counting using the logical sum of double coincidences in a TDCR array and defined solid angle counting taking into account activity inhomogeneity in the active deposit. The results show consistency between the three methods within a limit of a 0.3%. An ampoule of this solution will be sent to the International Reference System (SIR) during 2009. Uncertainties were analysed and compared in detail for the three applied methods. PMID:20031433

  14. Standardization of 241Am by digital coincidence counting, liquid scintillation counting and defined solid angle counting.

    PubMed

    Balpardo, C; Capoulat, M E; Rodrigues, D; Arenillas, P

    2010-01-01

    The nuclide (241)Am decays by alpha emission to (237)Np. Most of the decays (84.6%) populate the excited level of (237)Np with energy of 59.54 keV. Digital coincidence counting was applied to standardize a solution of (241)Am by alpha-gamma coincidence counting with efficiency extrapolation. Electronic discrimination was implemented with a pressurized proportional counter and the results were compared with two other independent techniques: Liquid scintillation counting using the logical sum of double coincidences in a TDCR array and defined solid angle counting taking into account activity inhomogeneity in the active deposit. The results show consistency between the three methods within a limit of a 0.3%. An ampoule of this solution will be sent to the International Reference System (SIR) during 2009. Uncertainties were analysed and compared in detail for the three applied methods.

  15. TCR usage, gene expression and function of two distinct FOXP3(+)Treg subsets within CD4(+)CD25(hi) T cells identified by expression of CD39 and CD45RO.

    PubMed

    Ye, Lingying; Goodall, Jane C; Zhang, Libin; Putintseva, Ekaterina V; Lam, Brian; Jiang, Lei; Liu, Wei; Yin, Jian; Lin, Li; Li, Ting; Wu, Xin; Yeo, Giles; Shugay, Mikhail; Chudakov, Dmitriy M; Gaston, Hill; Xu, Huji

    2016-03-01

    FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.

  16. Redefinition of the crater-density and absolute-age boundaries for the chronostratigraphic system of Mars

    USGS Publications Warehouse

    Werner, S.C.; Tanaka, K.L.

    2011-01-01

    For the boundaries of each chronostratigraphic epoch on Mars, we present systematically derived crater-size frequencies based on crater counts of geologic referent surfaces and three proposed " standard" crater size-frequency production distributions as defined by (a) a simple -2 power law, (b) Neukum and Ivanov, (c) Hartmann. In turn, these crater count values are converted to model-absolute ages based on the inferred cratering rate histories. We present a new boundary definition for the Late Hesperian-Early Amazonian transition. Our fitting of crater size-frequency distributions to the chronostratigraphic record of Mars permits the assignment of cumulative counts of craters down to 100. m, 1. km, 2. km, 5. km, and 16. km diameters to martian epochs. Due to differences in the " standard" crater size-frequency production distributions, a generalized crater-density-based definition to the chronostratigraphic system cannot be provided. For the diameter range used for the boundary definitions, the resulting model absolute age fits vary within 1.5% for a given set of production function and chronology model ages. Crater distributions translated to absolute ages utilizing different curve descriptions can result in absolute age differences exceeding 10%. ?? 2011 Elsevier Inc.

  17. Hanford whole body counting manual

    SciTech Connect

    Palmer, H.E.; Rieksts, G.A.; Lynch, T.P.

    1990-06-01

    This document describes the Hanford Whole Body Counting Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy--Richland Operations Office (DOE-RL) and its Hanford contractors. Program services include providing in vivo measurements of internally deposited radioactivity in Hanford employees (or visitors). Specific chapters of this manual deal with the following subjects: program operational charter, authority, administration, and practices, including interpreting applicable DOE Orders, regulations, and guidance into criteria for in vivo measurement frequency, etc., for the plant-wide whole body counting services; state-of-the-art facilities and equipment used to provide the best in vivo measurement results possible for the approximately 11,000 measurements made annually; procedures for performing the various in vivo measurements at the Whole Body Counter (WBC) and related facilities including whole body counts; operation and maintenance of counting equipment, quality assurance provisions of the program, WBC data processing functions, statistical aspects of in vivo measurements, and whole body counting records and associated guidance documents. 16 refs., 48 figs., 22 tabs.

  18. An absolute measure for a key currency

    NASA Astrophysics Data System (ADS)

    Oya, Shunsuke; Aihara, Kazuyuki; Hirata, Yoshito

    It is generally considered that the US dollar and the euro are the key currencies in the world and in Europe, respectively. However, there is no absolute general measure for a key currency. Here, we investigate the 24-hour periodicity of foreign exchange markets using a recurrence plot, and define an absolute measure for a key currency based on the strength of the periodicity. Moreover, we analyze the time evolution of this measure. The results show that the credibility of the US dollar has not decreased significantly since the Lehman shock, when the Lehman Brothers bankrupted and influenced the economic markets, and has increased even relatively better than that of the euro and that of the Japanese yen.

  19. Probing absolute spin polarization at the nanoscale.

    PubMed

    Eltschka, Matthias; Jäck, Berthold; Assig, Maximilian; Kondrashov, Oleg V; Skvortsov, Mikhail A; Etzkorn, Markus; Ast, Christian R; Kern, Klaus

    2014-12-10

    Probing absolute values of spin polarization at the nanoscale offers insight into the fundamental mechanisms of spin-dependent transport. Employing the Zeeman splitting in superconducting tips (Meservey-Tedrow-Fulde effect), we introduce a novel spin-polarized scanning tunneling microscopy that combines the probing capability of the absolute values of spin polarization with precise control at the atomic scale. We utilize our novel approach to measure the locally resolved spin polarization of magnetic Co nanoislands on Cu(111). We find that the spin polarization is enhanced by 65% when increasing the width of the tunnel barrier by only 2.3 Å due to the different decay of the electron orbitals into vacuum. PMID:25423049

  20. Absolute radiometry and the solar constant

    NASA Technical Reports Server (NTRS)

    Willson, R. C.

    1974-01-01

    A series of active cavity radiometers (ACRs) are described which have been developed as standard detectors for the accurate measurement of irradiance in absolute units. It is noted that the ACR is an electrical substitution calorimeter, is designed for automatic remote operation in any environment, and can make irradiance measurements in the range from low-level IR fluxes up to 30 solar constants with small absolute uncertainty. The instrument operates in a differential mode by chopping the radiant flux to be measured at a slow rate, and irradiance is determined from two electrical power measurements together with the instrumental constant. Results are reported for measurements of the solar constant with two types of ACRs. The more accurate measurement yielded a value of 136.6 plus or minus 0.7 mW/sq cm (1.958 plus or minus 0.010 cal/sq cm per min).

  1. From Hubble's NGSL to Absolute Fluxes

    NASA Technical Reports Server (NTRS)

    Heap, Sara R.; Lindler, Don

    2012-01-01

    Hubble's Next Generation Spectral Library (NGSL) consists of R-l000 spectra of 374 stars of assorted temperature, gravity, and metallicity. Each spectrum covers the wavelength range, 0.18-1.00 microns. The library can be viewed and/or downloaded from the website, http://archive.stsci.edu/prepds/stisngsll. Stars in the NGSL are now being used as absolute flux standards at ground-based observatories. However, the uncertainty in the absolute flux is about 2%, which does not meet the requirements of dark-energy surveys. We are therefore developing an observing procedure that should yield fluxes with uncertainties less than 1 % and will take part in an HST proposal to observe up to 15 stars using this new procedure.

  2. Impact of Winko on absolute discharges.

    PubMed

    Balachandra, Krishna; Swaminath, Sam; Litman, Larry C

    2004-01-01

    In Canada, case laws have had a significant impact on the way mentally ill offenders are managed, both in the criminal justice system and in the forensic mental health system. The Supreme Court of Canada's decision with respect to Winko has set a major precedent in the application of the test of significant risk to the safety of the public in making dispositions by the Ontario Review Board and granting absolute discharges to the mentally ill offenders in the forensic health system. Our study examines the impact of the Supreme Court of Canada's decision before and after Winko. The results show that the numbers of absolute discharges have increased post-Winko, which was statistically significant, but there could be other factors influencing this increase.

  3. Asteroid absolute magnitudes and slope parameters

    NASA Technical Reports Server (NTRS)

    Tedesco, Edward F.

    1991-01-01

    A new listing of absolute magnitudes (H) and slope parameters (G) has been created and published in the Minor Planet Circulars; this same listing will appear in the 1992 Ephemerides of Minor Planets. Unlike previous listings, the values of the current list were derived from fits of data at the V band. All observations were reduced in the same fashion using, where appropriate, a single basis default value of 0.15 for the slope parameter. Distances and phase angles were computed for each observation. The data for 113 asteroids was of sufficiently high quality to permit derivation of their H and G. These improved absolute magnitudes and slope parameters will be used to deduce the most reliable bias-corrected asteroid size-frequency distribution yet made.

  4. Absolute-magnitude distributions of supernovae

    SciTech Connect

    Richardson, Dean; Wright, John; Jenkins III, Robert L.; Maddox, Larry

    2014-05-01

    The absolute-magnitude distributions of seven supernova (SN) types are presented. The data used here were primarily taken from the Asiago Supernova Catalogue, but were supplemented with additional data. We accounted for both foreground and host-galaxy extinction. A bootstrap method is used to correct the samples for Malmquist bias. Separately, we generate volume-limited samples, restricted to events within 100 Mpc. We find that the superluminous events (M{sub B} < –21) make up only about 0.1% of all SNe in the bias-corrected sample. The subluminous events (M{sub B} > –15) make up about 3%. The normal Ia distribution was the brightest with a mean absolute blue magnitude of –19.25. The IIP distribution was the dimmest at –16.75.

  5. Absolute and relative dosimetry for ELIMED

    SciTech Connect

    Cirrone, G. A. P.; Schillaci, F.; Scuderi, V.; Cuttone, G.; Candiano, G.; Musumarra, A.; Pisciotta, P.; Romano, F.; Carpinelli, M.; Presti, D. Lo; Raffaele, L.; Tramontana, A.; Cirio, R.; Sacchi, R.; Monaco, V.; Marchetto, F.; Giordanengo, S.

    2013-07-26

    The definition of detectors, methods and procedures for the absolute and relative dosimetry of laser-driven proton beams is a crucial step toward the clinical use of this new kind of beams. Hence, one of the ELIMED task, will be the definition of procedures aiming to obtain an absolute dose measure at the end of the transport beamline with an accuracy as close as possible to the one required for clinical applications (i.e. of the order of 5% or less). Relative dosimetry procedures must be established, as well: they are necessary in order to determine and verify the beam dose distributions and to monitor the beam fluence and the energetic spectra during irradiations. Radiochromic films, CR39, Faraday Cup, Secondary Emission Monitor (SEM) and transmission ionization chamber will be considered, designed and studied in order to perform a fully dosimetric characterization of the ELIMED proton beam.

  6. Absolute photoionization cross sections of atomic oxygen

    NASA Technical Reports Server (NTRS)

    Samson, J. A. R.; Pareek, P. N.

    1985-01-01

    The absolute values of photoionization cross sections of atomic oxygen were measured from the ionization threshold to 120 A. An auto-ionizing resonance belonging to the 2S2P4(4P)3P(3Do, 3So) transition was observed at 479.43 A and another line at 389.97 A. The experimental data is in excellent agreement with rigorous close-coupling calculations that include electron correlations in both the initial and final states.

  7. Absolute photoionization cross sections of atomic oxygen

    NASA Technical Reports Server (NTRS)

    Samson, J. A. R.; Pareek, P. N.

    1982-01-01

    The absolute values of photoionization cross sections of atomic oxygen were measured from the ionization threshold to 120 A. An auto-ionizing resonance belonging to the 2S2P4(4P)3P(3Do, 3So) transition was observed at 479.43 A and another line at 389.97 A. The experimental data is in excellent agreement with rigorous close-coupling calculations that include electron correlations in both the initial and final states.

  8. Relative errors can cue absolute visuomotor mappings.

    PubMed

    van Dam, Loes C J; Ernst, Marc O

    2015-12-01

    When repeatedly switching between two visuomotor mappings, e.g. in a reaching or pointing task, adaptation tends to speed up over time. That is, when the error in the feedback corresponds to a mapping switch, fast adaptation occurs. Yet, what is learned, the relative error or the absolute mappings? When switching between mappings, errors with a size corresponding to the relative difference between the mappings will occur more often than other large errors. Thus, we could learn to correct more for errors with this familiar size (Error Learning). On the other hand, it has been shown that the human visuomotor system can store several absolute visuomotor mappings (Mapping Learning) and can use associated contextual cues to retrieve them. Thus, when contextual information is present, no error feedback is needed to switch between mappings. Using a rapid pointing task, we investigated how these two types of learning may each contribute when repeatedly switching between mappings in the absence of task-irrelevant contextual cues. After training, we examined how participants changed their behaviour when a single error probe indicated either the often-experienced error (Error Learning) or one of the previously experienced absolute mappings (Mapping Learning). Results were consistent with Mapping Learning despite the relative nature of the error information in the feedback. This shows that errors in the feedback can have a double role in visuomotor behaviour: they drive the general adaptation process by making corrections possible on subsequent movements, as well as serve as contextual cues that can signal a learned absolute mapping. PMID:26280315

  9. The absolute spectrophotometric catalog by Anita Cochran

    NASA Astrophysics Data System (ADS)

    Burnashev, V. I.; Burnasheva, B. A.; Ruban, E. V.; Hagen-Torn, E. I.

    2014-06-01

    The absolute spectrophotometric catalog by Anita Cochran is presented in a machine-readable form. The catalog systematizes observations acquired at the McDonald Observatory in 1977-1978. The data are compared with other sources, in particular, the calculated broadband stellar magnitudes are compared with photometric observations by other authors, to show that the observational data given in the catalog are reliable and suitable for a variety of applications. Observations of variable stars of different types make Cochran's catalog especially valuable.

  10. Absolute magnitudes and kinematics of barium stars.

    NASA Astrophysics Data System (ADS)

    Gomez, A. E.; Luri, X.; Grenier, S.; Prevot, L.; Mennessier, M. O.; Figueras, F.; Torra, J.

    1997-03-01

    The absolute magnitude of barium stars has been obtained from kinematical data using a new algorithm based on the maximum-likelihood principle. The method allows to separate a sample into groups characterized by different mean absolute magnitudes, kinematics and z-scale heights. It also takes into account, simultaneously, the censorship in the sample and the errors on the observables. The method has been applied to a sample of 318 barium stars. Four groups have been detected. Three of them show a kinematical behaviour corresponding to disk population stars. The fourth group contains stars with halo kinematics. The luminosities of the disk population groups spread a large range. The intrinsically brightest one (M_v_=-1.5mag, σ_M_=0.5mag) seems to be an inhomogeneous group containing barium binaries as well as AGB single stars. The most numerous group (about 150 stars) has a mean absolute magnitude corresponding to stars in the red giant branch (M_v_=0.9mag, σ_M_=0.8mag). The third group contains barium dwarfs, the obtained mean absolute magnitude is characteristic of stars on the main sequence or on the subgiant branch (M_v_=3.3mag, σ_M_=0.5mag). The obtained mean luminosities as well as the kinematical results are compatible with an evolutionary link between barium dwarfs and classical barium giants. The highly luminous group is not linked with these last two groups. More high-resolution spectroscopic data will be necessary in order to better discriminate between barium and non-barium stars.

  11. Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model

    PubMed Central

    Chang, De-Kuan; Peterson, Eric; Sun, Jiusong; Goudie, Calum; Drapkin, Ronny I.; Liu, Joyce F.; Matulonis, Ursula; Zhu, Quan; Marasco, Wayne A.

    2016-01-01

    ABSTRACT Recent studies have demonstrated that regulatory T cells (Tregs) are recruited to tumor sites where they can suppress antitumor immunity. The chemokine receptor CCR4 is expressed at high levels on functional CD4+CD25+FoxP3+ Tregs and production of the CCR4 ligand CCL22 by tumor cells and tumor-associated macrophages is associated with Treg recruitment to the tumor site. Here, we tested IgG1 and IgG4 isotypes of human anti-CCR4 mAb2-3 for their in vitro activity and in vivo capacity in a NSG mouse model bearing CCL22-secreting ovarian cancer (OvCA) xenograft to modulate Tregs and restore antitumor activity. Both mAb2-3 isotypes blocked in vitro chemoattraction of Tregs to CCL22-secreting OvCA cells. However, they differed in their in vivo mode of action with IgG1 causing Treg depletion and IgG4 blocking migration to the tumors. Primary T cells that were primed with OvCA-pulsed dendritic cells (DCs) demonstrated INFγ secretion that could be enhanced through Treg depletion by mAb2-3. Humanized mice reconstructed with allogeneic tumor-primed T cells (TP-T) were used to evaluate the restoration of OvCA immunity by depletion or blockade of Tregs with mAb2-3. We observed that IgG1 was more potent than IgG4 in inhibiting tumor growth. Mechanism studies demonstrated that mAb2-3 treatment lead to inhibition of IL-2 binding to its receptor. Further studies showed that mAb2-3 induced CD25 shedding (sCD25) from Tregs which lead to a decrease in IL-2-dependent survival. Together, the results demonstrate that mAb2-3 is an agonist antibody that can restore anti-OvCA immunity through modulation of Treg activity. PMID:27141347

  12. Chemical composition of French mimosa absolute oil.

    PubMed

    Perriot, Rodolphe; Breme, Katharina; Meierhenrich, Uwe J; Carenini, Elise; Ferrando, Georges; Baldovini, Nicolas

    2010-02-10

    Since decades mimosa (Acacia dealbata) absolute oil has been used in the flavor and perfume industry. Today, it finds an application in over 80 perfumes, and its worldwide industrial production is estimated five tons per year. Here we report on the chemical composition of French mimosa absolute oil. Straight-chain analogues from C6 to C26 with different functional groups (hydrocarbons, esters, aldehydes, diethyl acetals, alcohols, and ketones) were identified in the volatile fraction. Most of them are long-chain molecules: (Z)-heptadec-8-ene, heptadecane, nonadecane, and palmitic acid are the most abundant, and constituents such as 2-phenethyl alcohol, methyl anisate, and ethyl palmitate are present in smaller amounts. The heavier constituents were mainly triterpenoids such as lupenone and lupeol, which were identified as two of the main components. (Z)-Heptadec-8-ene, lupenone, and lupeol were quantified by GC-MS in SIM mode using external standards and represents 6%, 20%, and 7.8% (w/w) of the absolute oil. Moreover, odorant compounds were extracted by SPME and analyzed by GC-sniffing leading to the perception of 57 odorant zones, of which 37 compounds were identified by their odorant description, mass spectrum, retention index, and injection of the reference compound. PMID:20070087

  13. Measurement of absolute gravity acceleration in Firenze

    NASA Astrophysics Data System (ADS)

    de Angelis, M.; Greco, F.; Pistorio, A.; Poli, N.; Prevedelli, M.; Saccorotti, G.; Sorrentino, F.; Tino, G. M.

    2011-01-01

    This paper reports the results from the accurate measurement of the acceleration of gravity g taken at two separate premises in the Polo Scientifico of the University of Firenze (Italy). In these laboratories, two separate experiments aiming at measuring the Newtonian constant and testing the Newtonian law at short distances are in progress. Both experiments require an independent knowledge on the local value of g. The only available datum, pertaining to the italian zero-order gravity network, was taken more than 20 years ago at a distance of more than 60 km from the study site. Gravity measurements were conducted using an FG5 absolute gravimeter, and accompanied by seismic recordings for evaluating the noise condition at the site. The absolute accelerations of gravity at the two laboratories are (980 492 160.6 ± 4.0) μGal and (980 492 048.3 ± 3.0) μGal for the European Laboratory for Non-Linear Spectroscopy (LENS) and Dipartimento di Fisica e Astronomia, respectively. Other than for the two referenced experiments, the data here presented will serve as a benchmark for any future study requiring an accurate knowledge of the absolute value of the acceleration of gravity in the study region.

  14. A Methodology for Absolute Isotope Composition Measurement

    NASA Astrophysics Data System (ADS)

    Shen, J. J.; Lee, D.; Liang, W.

    2007-12-01

    Double spike technique was a well defined method for isotope composition measurement by TIMS of samples which have natural mass fractionation effect, but it is still a problem to define the isotope composition for double spike itself. In this study, we modified the old double spike technique and found that we could use the modified technique to solve the ¡§true¡¨ isotope composition of double spike itself. According the true isotope composition of double spike, we can measure the absolute isotope composition if the sample has natural fractionation effect. A new vector analytical method has been developed in order to obtain the true isotopic composition of a 42Ca-48Ca double spike, and this is achieved by using two different sample-spike mixtures combined with the double spike and the natural Ca data. Because the natural sample, the two mixtures, and the spike should all lie on a single mixing line, we are able to constrain the true isotopic composition of our double spike using this new approach. This method not only can be used in Ca system but also in Ti, Cr, Fe, Ni, Zn, Mo, Ba and Pb systems. The absolute double spike isotopic ratio is important, which can save a lot of time to check different reference standards. Especially for Pb, radiogenic isotope system, the decay systems embodied in three of four naturally occurring isotopes induce difficult to obtain true isotopic ratios for absolute dating.

  15. Chemical composition of French mimosa absolute oil.

    PubMed

    Perriot, Rodolphe; Breme, Katharina; Meierhenrich, Uwe J; Carenini, Elise; Ferrando, Georges; Baldovini, Nicolas

    2010-02-10

    Since decades mimosa (Acacia dealbata) absolute oil has been used in the flavor and perfume industry. Today, it finds an application in over 80 perfumes, and its worldwide industrial production is estimated five tons per year. Here we report on the chemical composition of French mimosa absolute oil. Straight-chain analogues from C6 to C26 with different functional groups (hydrocarbons, esters, aldehydes, diethyl acetals, alcohols, and ketones) were identified in the volatile fraction. Most of them are long-chain molecules: (Z)-heptadec-8-ene, heptadecane, nonadecane, and palmitic acid are the most abundant, and constituents such as 2-phenethyl alcohol, methyl anisate, and ethyl palmitate are present in smaller amounts. The heavier constituents were mainly triterpenoids such as lupenone and lupeol, which were identified as two of the main components. (Z)-Heptadec-8-ene, lupenone, and lupeol were quantified by GC-MS in SIM mode using external standards and represents 6%, 20%, and 7.8% (w/w) of the absolute oil. Moreover, odorant compounds were extracted by SPME and analyzed by GC-sniffing leading to the perception of 57 odorant zones, of which 37 compounds were identified by their odorant description, mass spectrum, retention index, and injection of the reference compound.

  16. The Carina Project: Absolute and Relative Calibrations

    NASA Astrophysics Data System (ADS)

    Corsi, C. E.; Bono, G.; Walker, A. R.; Brocato, E.; Buonanno, R.; Caputo, F.; Castellani, M.; Castellani, V.; Dall'Ora, M.; Marconi, M.; Monelli, M.; Nonino, M.; Pulone, L.; Ripepi, V.; Smith, H. A.

    We discuss the reduction strategy adopted to perform the relative and the absolute calibration of the Wide Field Imager (WFI) available at the 2.2m ESO/MPI telescope and of the Mosaic Camera (MC) available at the 4m CTIO Blanco telescope. To properly constrain the occurrence of deceptive systematic errors in the relative calibration we observed with each chip the same set of stars. Current photometry seems to suggest that the WFI shows a positional effect when moving from the top to the bottom of individual chips. Preliminary results based on an independent data set collected with the MC suggest that this camera is only marginally affected by the same problem. To perform the absolute calibration we observed with each chip the same set of standard stars. The sample covers a wide color range and the accuracy both in the B and in the V-band appears to be of the order of a few hundredths of magnitude. Finally, we briefly outline the observing strategy to improve both relative and absolute calibrations of mosaic CCD cameras.

  17. LINEAR COUNT-RATE METER

    DOEpatents

    Henry, J.J.

    1961-09-01

    A linear count-rate meter is designed to provide a highly linear output while receiving counting rates from one cycle per second to 100,000 cycles per second. Input pulses enter a linear discriminator and then are fed to a trigger circuit which produces positive pulses of uniform width and amplitude. The trigger circuit is connected to a one-shot multivibrator. The multivibrator output pulses have a selected width. Feedback means are provided for preventing transistor saturation in the multivibrator which improves the rise and decay times of the output pulses. The multivibrator is connected to a diode-switched, constant current metering circuit. A selected constant current is switched to an averaging circuit for each pulse received, and for a time determined by the received pulse width. The average output meter current is proportional to the product of the counting rate, the constant current, and the multivibrator output pulse width.

  18. Photon Counting - One More Time

    NASA Astrophysics Data System (ADS)

    Stanton, Richard H.

    2012-05-01

    Photon counting has been around for more than 60 years, and has been available to amateurs for most of that time. In most cases single photons are detected using photomultiplier tubes, "old technology" that became available after the Second World War. But over the last couple of decades the perfection of CCD devices has given amateurs the ability to perform accurate photometry with modest telescopes. Is there any reason to still count photons? This paper discusses some of the strengths of current photon counting technology, particularly relating to the search for fast optical transients. Technology advances in counters and photomultiplier modules are briefly mentioned. Illustrative data are presented including FFT analysis of bright star photometry and a technique for finding optical pulses in a large file of noisy data. This latter technique is shown to enable the discovery of a possible optical flare on the polar variable AM Her.

  19. IL-35 improves Treg-mediated immune suppression in atherosclerotic mice

    PubMed Central

    Tao, Linlin; Zhu, Jie; Chen, Yuefeng; Wang, Qinghang; Pan, Ying; Yu, Qianqian; Zhou, Birong; Zhu, Huaqing

    2016-01-01

    Interleukin (IL)-35 is an anti-inflammatory cytokine that may have a protective role in atherosclerosis (AS). However, the exact role of IL-35 in the disease, and the etiology of AS, remain incompletely understood. The present study aimed to investigate whether exogenous IL-35 was able to attenuate the formation of atherosclerotic lesions in apoE−/− mice, and analyze alterations in the expression levels of forkhead box protein 3 (Foxp3) in peripheral blood and the lesions during the progression of AS. ApoE−/− mice were randomly divided into two groups that received either a basal diet (negative control group) or a high-fat diet (HFD) for 4 weeks. The HFD group was further subdivided into groups that received IL-35, atorvastatin or no treatment for 12 weeks. Diagnostic enzyme assay kits were applied for the detection of plasma lipids, and hematoxylin and eosin staining was used to analyze the severity of atherosclerotic lesions in apoE−/− mice. Immunohistochemistry and flow cytometry were performed to analyze the expression of Foxp3 in the plasma and atherosclerotic plaques. As compared with the negative control group, the plasma lipids were significantly increased, and the lesions were obviously formed, in the HFD groups. Furthermore, the area of the lesion was reduced in IL-35- and atorvastatin-treated groups, as compared with the AS control group. In addition, Foxp3 expression was upregulated in the plasma and lesions of the IL-35- and atorvastatin-treated groups, as compared with the AS control group. The present study demonstrated that IL-35 improved Treg-mediated immune suppression in atherosclerotic mice, thus suggesting that IL-35 may be a novel therapeutic target for AS.

  20. IL-35 improves Treg-mediated immune suppression in atherosclerotic mice

    PubMed Central

    Tao, Linlin; Zhu, Jie; Chen, Yuefeng; Wang, Qinghang; Pan, Ying; Yu, Qianqian; Zhou, Birong; Zhu, Huaqing

    2016-01-01

    Interleukin (IL)-35 is an anti-inflammatory cytokine that may have a protective role in atherosclerosis (AS). However, the exact role of IL-35 in the disease, and the etiology of AS, remain incompletely understood. The present study aimed to investigate whether exogenous IL-35 was able to attenuate the formation of atherosclerotic lesions in apoE−/− mice, and analyze alterations in the expression levels of forkhead box protein 3 (Foxp3) in peripheral blood and the lesions during the progression of AS. ApoE−/− mice were randomly divided into two groups that received either a basal diet (negative control group) or a high-fat diet (HFD) for 4 weeks. The HFD group was further subdivided into groups that received IL-35, atorvastatin or no treatment for 12 weeks. Diagnostic enzyme assay kits were applied for the detection of plasma lipids, and hematoxylin and eosin staining was used to analyze the severity of atherosclerotic lesions in apoE−/− mice. Immunohistochemistry and flow cytometry were performed to analyze the expression of Foxp3 in the plasma and atherosclerotic plaques. As compared with the negative control group, the plasma lipids were significantly increased, and the lesions were obviously formed, in the HFD groups. Furthermore, the area of the lesion was reduced in IL-35- and atorvastatin-treated groups, as compared with the AS control group. In addition, Foxp3 expression was upregulated in the plasma and lesions of the IL-35- and atorvastatin-treated groups, as compared with the AS control group. The present study demonstrated that IL-35 improved Treg-mediated immune suppression in atherosclerotic mice, thus suggesting that IL-35 may be a novel therapeutic target for AS. PMID:27698748

  1. Reticulocyte counting using flow cytometry.

    PubMed

    Nobes, P R; Carter, A B

    1990-08-01

    A flow cytometric method for the quantitation of reticulocytes was refined for routine laboratory use. Blood (2 microliters) is added to 2 ml of 0.4 microM thiazole orange in phosphate buffered saline, incubated at room temperature for 90 minutes, and analysed on a Coulter EPICS Profile flow cytometer, with gating for red cells on the basis of forward and right angled light scatter. Blood (2 microliters) is also incubated with phosphate buffered saline alone as an unstained control. The adult reference range (mean +/- 2 SD), established from 30 laboratory personnel, is 19.4-59.2 x 10(9)/l (0.2-1.6%). Comparison of this technique was made on 39 selected patient samples with visual counting of cells stained with brilliant cresyl blue. The correlation between the two methods was 0.99 with slope 0.96 and intercept 0.02. The precision of the automated technique in three subjects with reticulocyte counts of 0.12%, 1.84%, and 14.3% was 33.3%, 7.3%, and 1.4%, respectively (coefficient of variations). In three patients studied serially after intensive chemotherapy, in whom the reticulocyte count quantitated by routine visual methods approached zero (0-0.1%) for eight to 18 days, the automated counts varied between 0 and 0.5%. Flow cytometric reticulocyte counting is thus a simple and highly reliable methodology for the quantitation of normal and raised reticulocyte counts but cannot be reliably used to quantitate a subnormal level.

  2. GalaxyCount: Galaxy counts and variance calculator

    NASA Astrophysics Data System (ADS)

    Bland-Hawthorn, Joss; Ellis, Simon

    2013-12-01

    GalaxyCount calculates the number and standard deviation of galaxies in a magnitude limited observation of a given area. The methods to calculate both the number and standard deviation may be selected from different options. Variances may be computed for circular, elliptical and rectangular window functions.

  3. Precision absolute value amplifier for a precision voltmeter

    DOEpatents

    Hearn, William E.; Rondeau, Donald J.

    1985-01-01

    Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resister is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resister. The output current through the load resister is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resister. A second gain determining resister is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

  4. Precision absolute-value amplifier for a precision voltmeter

    DOEpatents

    Hearn, W.E.; Rondeau, D.J.

    1982-10-19

    Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resistor is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resistor. The output current through the load resistor is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resistor. A second gain determining resistor is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

  5. The absolute radiometric calibration of space-based sensors

    NASA Astrophysics Data System (ADS)

    Holm, Ronald Gene

    A reflectance based inflight calibration procedure is used to determine the radiance reaching the entrance pupil of a sensor. This procedure uses ground based measurements coupled with a radiative transfer code to characterize the effects the atmosphere has on the signal reaching the sensor. The computed radiance is compared to the digital count output of the sensor associated with the image of a test site. This provides an update to the preflight calibration of the system and a check on the on-board internal calibrator. This calibration procedure was used to perform a series of 5 calibrations of the LANDSAT-5 Thematic Mapper. The absolute calibration techniques were put to another test with a series of 3 calibration of the SPOT-1 High Resolution Visible sensors. The procedure for performing a satellite calibration was then used to demonstrate how a calibrated satellite sensor can be used to quantitatively evaluate surface reflectance over a wide range of surface features. Predicted reflectance factors were compared to values obtained from aircraft based radiometer data. A strong correlation was shown between reflectance values determined from satellite imagery and low flying aircraft data.

  6. Association of Notch pathway down-regulation with Triple Negative/Basal-like breast carcinomas and high tumor-infiltrating FOXP3+ Tregs.

    PubMed

    Ortiz-Martínez, Fernando; Gutiérrez-Aviñó, Francisco José; Sanmartín, Elena; Pomares-Navarro, Eloy; Villalba-Riquelme, Cristina; García-Martínez, Araceli; Lerma, Enrique; Peiró, Gloria

    2016-06-01

    T regulatory cells (Tregs) are a lineage of lymphocytes involved in immune response suppression that are characterized by the expression of the forkhead box P3 (FOXP3) transcription factor. Notch pathway regulates FOXP3 transcription in Tregs, but its role in breast cancer is unknown. We aimed at studying whether Notch pathway regulates FOXP3 expression and Tregs content in breast cancer, and its association with luminal breast carcinomas. We analyzed by quantitative Real-Time PCR the mRNA levels of FOXP3, Notch pathway genes (Notch1, Notch2, Notch4 and Jagged1) and STAT3 in a series of 152 breast carcinomas including hormone receptor-positive and -negative phenotypes (luminal and Triple Negative/Basal-like). We also studied the protein expression of Notch1, STAT3 and FOXP3 by immunohistochemistry. High FOXP3 mRNA levels correlated with larger tumor size (p=0.010), histological grade 3 (p=0.008) and positive lymph-node status (p=0.031). Also, low levels of Notch pathway genes mRNA correlated with poor prognostic factors such as larger tumor size, positive lymph-node status, tumor phenotype and infiltrating tumor Tregs. A survival analysis for the patients showed that large tumor size, histological grade 3, vascular invasion, infiltrating Tregs and low Notch1 mRNA expression were significantly associated with a decreased patients' overall survival (p≤0.05). On a multivariate analysis, high Tregs content (HR=3.00, 95% CI 1.04-8.90, p=0.042) and low Notch1 mRNA levels (HR=3.33, 95% CI 1.02-10.86, p=0.046) were independent markers for overall survival. Our results support that the Notch pathway up-regulation promotes luminal breast carcinomas, whereas down-regulation correlates with the expression of FOXP3, favors tumor Tregs infiltration and associates with Triple Negative/Basal-like tumors. PMID:27118257

  7. WBC (White Blood Cell) Differential Count

    MedlinePlus

    ... Results of a differential are usually reported as absolute values of the five types of WBCs and/or ... a percent of the total number of WBCs. Absolute values are calculated by multiplying the total number of ...

  8. South Carolina Kids Count, 2001.

    ERIC Educational Resources Information Center

    Holmes, A. Baron

    This Kids Count report examines statewide trends in the well-being of South Carolina's children. The statistical portrait is based on 42 indicators in the areas of demographics, family, economic status, health, readiness and early school performance, scholastic achievement, and adolescent risk behaviors. The indicators are: (1) population; (2)…

  9. South Carolina Kids Count, 2000.

    ERIC Educational Resources Information Center

    Holmes, A. Baron

    This Kids Count report examines statewide trends in the well-being of South Carolina's children. The statistical portrait is based on 41 indicators in the areas of demographics, family, economic status, health, readiness and early school performance, scholastic achievement, and adolescent risk behaviors. The indicators are: (1) population; (2)…

  10. Kids Count Data Sheet, 2000.

    ERIC Educational Resources Information Center

    Annie E. Casey Foundation, Baltimore, MD.

    Data from the 50 United States are listed for 1997 from Kids Count in an effort to track state-by-state the status of children in the United States and to secure better futures for all children. Data include percent low birth weight babies; infant mortality rate; child death rate; rate of teen deaths by accident, homicide, and suicide; teen birth…

  11. Counting a Culture of Mealworms

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2007-01-01

    Math is not the only topic that will be discussed when young children are asked to care for and count "mealworms," a type of insect larvae (just as caterpillars are the babies of butterflies, these larvae are babies of beetles). The following activity can take place over two months as the beetles undergo metamorphosis from larvae to adults. As the…

  12. Oklahoma Kids Count Factbook '96.

    ERIC Educational Resources Information Center

    Ingraham, Sandy

    This data book presents findings of the Kids Count Project on current conditions faced by Oklahoma children age birth through 18. This second annual factbook organizes state and county data over a period of time to enable conditions for children in each county to be compared and ranked. The benchmark indicators studied include low birthweight…

  13. Kids Count New Hampshire, 1996.

    ERIC Educational Resources Information Center

    Terry, Susan Palmer; Hall, Douglas E.

    This Kids Count report presents statewide trends in the well-being of New Hampshire's children. The statistical report is based on 14 indicators of child well being: (1) children in poverty; (2) fatherless families; (3) maternal education; (4) teen births; (5) births to unmarried mothers; (6) low birth weight births; (7) insurance coverage; (8)…

  14. Wiskids Count Data Book, 2003.

    ERIC Educational Resources Information Center

    Cranley, M. Martha; Bianchi, J. P.; Eleson, Charity; Hall, Linda; Jacobson, Bob; Jackson, Kristin; Peacock, Jon

    This WisKids Count data book provides a statistical portrait of the well-being of Wisconsin's children. In addition to demographic data indicating changing communities, the indicators and data are organized into five overarching goals: (1) Healthy Families and Children Thrive, including births to single women, infant deaths, and health care…

  15. KIDS COUNT Data Brief, 2009

    ERIC Educational Resources Information Center

    Annie E. Casey Foundation, 2009

    2009-01-01

    This 2009 KIDS COUNT Data Brief features highlights of the enhanced, mobile-friendly Data Center; data on the 10 key indicators of child well-being for all U.S. states, the District of Columbia, and many cities, counties, and school districts; and a summary of this year's essay, which calls for improvements to the nation's ability to design and…

  16. Shakespeare Live! and Character Counts.

    ERIC Educational Resources Information Center

    Brookshire, Cathy A.

    This paper discusses a live production of Shakespeare's "Macbeth" (in full costume but with no sets) for all public middle school and high school students in Harrisonburg and Rockingham, Virginia. The paper states that the "Character Counts" issues that are covered in the play are: decision making, responsibility and citizenship, trustworthiness,…

  17. Kids Count in Colorado! 2003.

    ERIC Educational Resources Information Center

    Boeke, Kaye

    This Kids Count report examines state, county, and regional trends in the well-being of Colorado's children. The first part of the report is presented in four chapters. Chapter 1 includes findings regarding the increasing diversity of the child population, linguistic isolation, the impact of parental unemployment, child poverty, and the affordable…

  18. On Counting the Rational Numbers

    ERIC Educational Resources Information Center

    Almada, Carlos

    2010-01-01

    In this study, we show how to construct a function from the set N of natural numbers that explicitly counts the set Q[superscript +] of all positive rational numbers using a very intuitive approach. The function has the appeal of Cantor's function and it has the advantage that any high school student can understand the main idea at a glance…

  19. Verbal Counting in Bilingual Contexts

    ERIC Educational Resources Information Center

    Donevska-Todorova, Ana

    2015-01-01

    Informal experiences in mathematics often include playful competitions among young children in counting numbers in as many as possible different languages. Can these enjoyable experiences result with excellence in the formal processes of education? This article discusses connections between mathematical achievements and natural languages within…

  20. Wyoming Kids Count Factbook, 1997.

    ERIC Educational Resources Information Center

    Wyoming Kids Count, Cheyenne.

    This Kids Count factbook details statewide trends in the well-being of Wyoming's children. The 1997 report has been expanded to include detailed information on the status of children by categories of welfare, health, and education. The first part of the factbook documents trends by county for 15 indicators: (1) poverty and population; (2)…

  1. KIDS COUNT New Hampshire, 2000.

    ERIC Educational Resources Information Center

    Shemitz, Elllen, Ed.

    This Kids Count report presents statewide trends in the well-being of New Hampshire's children. The statistical report is based on 22 indicators of child well-being in 5 interrelated areas: (1) children and families (including child population, births, children living with single parent, and children experiencing parental divorce); (2) economic…

  2. Meal Counting and Claiming Manual.

    ERIC Educational Resources Information Center

    Food and Nutrition Service (USDA), Washington, DC.

    This manual contains information about the selection and implementation of a meal counting and claiming system for the National School Lunch Program (NSLP) and the School Breakfast Program (BSP). Federal reimbursement is provided for each meal that meets program requirements and is served to an eligible student. Part 1 explains the six elements of…

  3. Absolute Radiometric Calibration of EUNIS-06

    NASA Technical Reports Server (NTRS)

    Thomas, R. J.; Rabin, D. M.; Kent, B. J.; Paustian, W.

    2007-01-01

    The Extreme-Ultraviolet Normal-Incidence Spectrometer (EUNIS) is a soundingrocket payload that obtains imaged high-resolution spectra of individual solar features, providing information about the Sun's corona and upper transition region. Shortly after its successful initial flight last year, a complete end-to-end calibration was carried out to determine the instrument's absolute radiometric response over its Longwave bandpass of 300 - 370A. The measurements were done at the Rutherford-Appleton Laboratory (RAL) in England, using the same vacuum facility and EUV radiation source used in the pre-flight calibrations of both SOHO/CDS and Hinode/EIS, as well as in three post-flight calibrations of our SERTS sounding rocket payload, the precursor to EUNIS. The unique radiation source provided by the Physikalisch-Technische Bundesanstalt (PTB) had been calibrated to an absolute accuracy of 7% (l-sigma) at 12 wavelengths covering our bandpass directly against the Berlin electron storage ring BESSY, which is itself a primary radiometric source standard. Scans of the EUNIS aperture were made to determine the instrument's absolute spectral sensitivity to +- 25%, considering all sources of error, and demonstrate that EUNIS-06 was the most sensitive solar E W spectrometer yet flown. The results will be matched against prior calibrations which relied on combining measurements of individual optical components, and on comparisons with theoretically predicted 'insensitive' line ratios. Coordinated observations were made during the EUNIS-06 flight by SOHO/CDS and EIT that will allow re-calibrations of those instruments as well. In addition, future EUNIS flights will provide similar calibration updates for TRACE, Hinode/EIS, and STEREO/SECCHI/EUVI.

  4. Clock time is absolute and universal

    NASA Astrophysics Data System (ADS)

    Shen, Xinhang

    2015-09-01

    A critical error is found in the Special Theory of Relativity (STR): mixing up the concepts of the STR abstract time of a reference frame and the displayed time of a physical clock, which leads to use the properties of the abstract time to predict time dilation on physical clocks and all other physical processes. Actually, a clock can never directly measure the abstract time, but can only record the result of a physical process during a period of the abstract time such as the number of cycles of oscillation which is the multiplication of the abstract time and the frequency of oscillation. After Lorentz Transformation, the abstract time of a reference frame expands by a factor gamma, but the frequency of a clock decreases by the same factor gamma, and the resulting multiplication i.e. the displayed time of a moving clock remains unchanged. That is, the displayed time of any physical clock is an invariant of Lorentz Transformation. The Lorentz invariance of the displayed times of clocks can further prove within the framework of STR our earth based standard physical time is absolute, universal and independent of inertial reference frames as confirmed by both the physical fact of the universal synchronization of clocks on the GPS satellites and clocks on the earth, and the theoretical existence of the absolute and universal Galilean time in STR which has proved that time dilation and space contraction are pure illusions of STR. The existence of the absolute and universal time in STR has directly denied that the reference frame dependent abstract time of STR is the physical time, and therefore, STR is wrong and all its predictions can never happen in the physical world.

  5. Achieving Climate Change Absolute Accuracy in Orbit

    NASA Technical Reports Server (NTRS)

    Wielicki, Bruce A.; Young, D. F.; Mlynczak, M. G.; Thome, K. J; Leroy, S.; Corliss, J.; Anderson, J. G.; Ao, C. O.; Bantges, R.; Best, F.; Bowman, K.; Brindley, H.; Butler, J. J.; Collins, W.; Dykema, J. A.; Doelling, D. R.; Feldman, D. R.; Fox, N.; Huang, X.; Holz, R.; Huang, Y.; Jennings, D.; Jin, Z.; Johnson, D. G.; Jucks, K.; Kato, S.; Kratz, D. P.; Liu, X.; Lukashin, C.; Mannucci, A. J.; Phojanamongkolkij, N.; Roithmayr, C. M.; Sandford, S.; Taylor, P. C.; Xiong, X.

    2013-01-01

    The Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission will provide a calibration laboratory in orbit for the purpose of accurately measuring and attributing climate change. CLARREO measurements establish new climate change benchmarks with high absolute radiometric accuracy and high statistical confidence across a wide range of essential climate variables. CLARREO's inherently high absolute accuracy will be verified and traceable on orbit to Système Internationale (SI) units. The benchmarks established by CLARREO will be critical for assessing changes in the Earth system and climate model predictive capabilities for decades into the future as society works to meet the challenge of optimizing strategies for mitigating and adapting to climate change. The CLARREO benchmarks are derived from measurements of the Earth's thermal infrared spectrum (5-50 micron), the spectrum of solar radiation reflected by the Earth and its atmosphere (320-2300 nm), and radio occultation refractivity from which accurate temperature profiles are derived. The mission has the ability to provide new spectral fingerprints of climate change, as well as to provide the first orbiting radiometer with accuracy sufficient to serve as the reference transfer standard for other space sensors, in essence serving as a "NIST [National Institute of Standards and Technology] in orbit." CLARREO will greatly improve the accuracy and relevance of a wide range of space-borne instruments for decadal climate change. Finally, CLARREO has developed new metrics and methods for determining the accuracy requirements of climate observations for a wide range of climate variables and uncertainty sources. These methods should be useful for improving our understanding of observing requirements for most climate change observations.

  6. Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

    PubMed Central

    2013-01-01

    Background Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. PMID:23638998

  7. Absolute calibration of the Auger fluorescence detectors

    SciTech Connect

    Bauleo, P.; Brack, J.; Garrard, L.; Harton, J.; Knapik, R.; Meyhandan, R.; Rovero, A.C.; Tamashiro, A.; Warner, D.

    2005-07-01

    Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a light source at the telescope aperture. The technique accounts for the combined effects of all detector components in a single measurement. The calibrated 2.5 m diameter light source fills the aperture, providing uniform illumination to each pixel. The known flux from the light source and the response of the acquisition system give the required calibration for each pixel. In the lab, light source uniformity is studied using CCD images and the intensity is measured relative to NIST-calibrated photodiodes. Overall uncertainties are presently 12%, and are dominated by systematics.

  8. Absolute rate theories of epigenetic stability

    NASA Astrophysics Data System (ADS)

    Walczak, Aleksandra M.; Onuchic, José N.; Wolynes, Peter G.

    2005-12-01

    Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of the rare cellular states that allow epigenetic escape and the transmission factor depend on the rates of DNA binding and unbinding events and on the rates of protein synthesis and degradation. Different mechanisms of escape from the stable attractors occur in the nonadiabatic, weakly adiabatic, and strictly adiabatic regimes, characterized by the relative values of those input rates. rate theory | stochastic gene expression | gene switches

  9. Characterization of the DARA solar absolute radiometer

    NASA Astrophysics Data System (ADS)

    Finsterle, W.; Suter, M.; Fehlmann, A.; Kopp, G.

    2011-12-01

    The Davos Absolute Radiometer (DARA) prototype is an Electrical Substitution Radiometer (ESR) which has been developed as a successor of the PMO6 type on future space missions and ground based TSI measurements. The DARA implements an improved thermal design of the cavity detector and heat sink assembly to minimize air-vacuum differences and to maximize thermal symmetry of measuring and compensating cavity. The DARA also employs an inverted viewing geometry to reduce internal stray light. We will report on the characterization and calibration experiments which were carried out at PMOD/WRC and LASP (TRF).

  10. Absolute Priority for a Vehicle in VANET

    NASA Astrophysics Data System (ADS)

    Shirani, Rostam; Hendessi, Faramarz; Montazeri, Mohammad Ali; Sheikh Zefreh, Mohammad

    In today's world, traffic jams waste hundreds of hours of our life. This causes many researchers try to resolve the problem with the idea of Intelligent Transportation System. For some applications like a travelling ambulance, it is important to reduce delay even for a second. In this paper, we propose a completely infrastructure-less approach for finding shortest path and controlling traffic light to provide absolute priority for an emergency vehicle. We use the idea of vehicular ad-hoc networking to reduce the imposed travelling time. Then, we simulate our proposed protocol and compare it with a centrally controlled traffic light system.

  11. Absolute method of measuring magnetic susceptibility

    USGS Publications Warehouse

    Thorpe, A.; Senftle, F.E.

    1959-01-01

    An absolute method of standardization and measurement of the magnetic susceptibility of small samples is presented which can be applied to most techniques based on the Faraday method. The fact that the susceptibility is a function of the area under the curve of sample displacement versus distance of the magnet from the sample, offers a simple method of measuring the susceptibility without recourse to a standard sample. Typical results on a few substances are compared with reported values, and an error of less than 2% can be achieved. ?? 1959 The American Institute of Physics.

  12. Lactobacillus plantarum NCU116 Attenuates Cyclophosphamide-Induced Immunosuppression and Regulates Th17/Treg Cell Immune Responses in Mice.

    PubMed

    Xie, Junhua; Nie, Shaoping; Yu, Qiang; Yin, Junyi; Xiong, Tao; Gong, Deming; Xie, Mingyong

    2016-02-17

    The balance of T helper cells 17 (Th17)/regulatory T cells (Treg) plays a key role in maintaining a normal immune response. It is well-known that cyclophosphamide (CTX) applied at high dose often damages the immune system by inhibiting immune cell proliferation. In this study, the immunomodulating effects of Lactobacillus plantarum NCU116 in CTX-induced immunosuppression mice were investigated. Results showed that the levels of cytokines interleukin (IL)-17 and IL-21 were significantly increased after 10 days of treatment with a high dose of NCU116 (46.92 ± 4.28 and 119.92 ± 10.89, respectively) compared with the model group (36.20 ± 2.63, 61.00 ± 6.92, respectively), and the levels of cytokines IL-23 and TGF-β3 of the three NCU116 treatment groups were significantly higher than that of the model group (90.48 ± 6.33 and 140.45 ± 14.30, respectively) (p < 0.05) and close to 62 and 69% of the normal group's level (140.98 ± 14.74 and 266.95 ± 23.11, respectively) at 10 days. The bacterium was also found to increase the expression levels of Th17 immune response and Treg immune response specific transcription factors RORγt and Foxp3. In addition, the bacterium significantly increased the number of CD4(+)T cells and dendrtic cells (DCs) and up-regulated mRNA expression of Toll-like receptors (TLRs). These findings demonstrated that NCU116 has the potential ability to enhance intestinal mucosa immunity and regulate the Th17/Treg balance, which may be attributed to the TLR pathway in DCs.

  13. Prognostic value of parameters derived from white blood cell and differential counts in patients receiving palliative radiotherapy

    PubMed Central

    Saito, Tetsuo; Toya, Ryo; Matsuyama, Tomohiko; Semba, Akiko; Matsuyama, Keiya; Oya, Natsuo

    2016-01-01

    The aim of the present study was to identify white blood cell (WBC) parameters with high prognostic value for the survival of patients receiving palliative radiotherapy. The prognostic value of seven parameters derived from WBC and differential counts was retrospectively evaluated in patients who underwent palliative radiotherapy between October, 2010 and June, 2013. The analyzed parameters were the total WBC count, the absolute and relative lymphocyte count, the absolute and relative neutrophil count, and the neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios. Following univariate analysis, multivariate Cox regression analysis was performed to adjust for gender, age, disease type, previous chemotherapy, previous radiotherapy and the levels of albumin and lactate dehydrogenase. A total of 220 patients with a median survival of 4.7 months were identified. All seven parameters were found to be statistically significant predictors of survival on univariate Cox regression analysis (P<0.05). Of these parameters, the low relative lymphocyte and high relative neutrophil counts were consistent predictors of poor survival in patients who received chemotherapy within 1 month prior to blood sampling (n=68) and in patients who received steroid treatment at the time of sampling (n=49). Multivariate Cox regression analysis revealed that the relative lymphocyte and neutrophil counts were independent predictors of survival in all 220 patients (P<0.05). In conclusion, relative lymphocyte and neutrophil counts were of high prognostic value for the survival of patients receiving palliative radiotherapy, even in those receiving medications that affect WBC and differential counts. PMID:27602221

  14. Prognostic value of parameters derived from white blood cell and differential counts in patients receiving palliative radiotherapy

    PubMed Central

    Saito, Tetsuo; Toya, Ryo; Matsuyama, Tomohiko; Semba, Akiko; Matsuyama, Keiya; Oya, Natsuo

    2016-01-01

    The aim of the present study was to identify white blood cell (WBC) parameters with high prognostic value for the survival of patients receiving palliative radiotherapy. The prognostic value of seven parameters derived from WBC and differential counts was retrospectively evaluated in patients who underwent palliative radiotherapy between October, 2010 and June, 2013. The analyzed parameters were the total WBC count, the absolute and relative lymphocyte count, the absolute and relative neutrophil count, and the neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios. Following univariate analysis, multivariate Cox regression analysis was performed to adjust for gender, age, disease type, previous chemotherapy, previous radiotherapy and the levels of albumin and lactate dehydrogenase. A total of 220 patients with a median survival of 4.7 months were identified. All seven parameters were found to be statistically significant predictors of survival on univariate Cox regression analysis (P<0.05). Of these parameters, the low relative lymphocyte and high relative neutrophil counts were consistent predictors of poor survival in patients who received chemotherapy within 1 month prior to blood sampling (n=68) and in patients who received steroid treatment at the time of sampling (n=49). Multivariate Cox regression analysis revealed that the relative lymphocyte and neutrophil counts were independent predictors of survival in all 220 patients (P<0.05). In conclusion, relative lymphocyte and neutrophil counts were of high prognostic value for the survival of patients receiving palliative radiotherapy, even in those receiving medications that affect WBC and differential counts.

  15. Sentinel-2/MSI absolute calibration: first results

    NASA Astrophysics Data System (ADS)

    Lonjou, V.; Lachérade, S.; Fougnie, B.; Gamet, P.; Marcq, S.; Raynaud, J.-L.; Tremas, T.

    2015-10-01

    Sentinel-2 is an optical imaging mission devoted to the operational monitoring of land and coastal areas. It is developed in partnership between the European Commission and the European Space Agency. The Sentinel-2 mission is based on a satellites constellation deployed in polar sun-synchronous orbit. It will offer a unique combination of global coverage with a wide field of view (290km), a high revisit (5 days with two satellites), a high resolution (10m, 20m and 60m) and multi-spectral imagery (13 spectral bands in visible and shortwave infra-red domains). CNES is involved in the instrument commissioning in collaboration with ESA. This paper reviews all the techniques that will be used to insure an absolute calibration of the 13 spectral bands better than 5% (target 3%), and will present the first results if available. First, the nominal calibration technique, based on an on-board sun diffuser, is detailed. Then, we show how vicarious calibration methods based on acquisitions over natural targets (oceans, deserts, and Antarctica during winter) will be used to check and improve the accuracy of the absolute calibration coefficients. Finally, the verification scheme, exploiting photometer in-situ measurements over Lacrau plain, is described. A synthesis, including spectral coherence, inter-methods agreement and temporal evolution, will conclude the paper.

  16. Experimental results for absolute cylindrical wavefront testing

    NASA Astrophysics Data System (ADS)

    Reardon, Patrick J.; Alatawi, Ayshah

    2014-09-01

    Applications for Cylindrical and near-cylindrical surfaces are ever-increasing. However, fabrication of high quality cylindrical surfaces is limited by the difficulty of accurate and affordable metrology. Absolute testing of such surfaces represents a challenge to the optical testing community as cylindrical reference wavefronts are difficult to produce. In this paper, preliminary results for a new method of absolute testing of cylindrical wavefronts are presented. The method is based on the merging of the random ball test method with the fiber optic reference test. The random ball test assumes a large number of interferograms of a good quality sphere with errors that are statistically distributed such that the average of the errors goes to zero. The fiber optic reference test utilizes a specially processed optical fiber to provide a clean high quality reference wave from an incident line focus from the cylindrical wave under test. By taking measurements at different rotation and translations of the fiber, an analogous procedure can be employed to determine the quality of the converging cylindrical wavefront with high accuracy. This paper presents and discusses the results of recent tests of this method using a null optic formed by a COTS cylindrical lens and a free-form polished corrector element.

  17. Absolute Electron Extraction Efficiency of Liquid Xenon

    NASA Astrophysics Data System (ADS)

    Kamdin, Katayun; Mizrachi, Eli; Morad, James; Sorensen, Peter

    2016-03-01

    Dual phase liquid/gas xenon time projection chambers (TPCs) currently set the world's most sensitive limits on weakly interacting massive particles (WIMPs), a favored dark matter candidate. These detectors rely on extracting electrons from liquid xenon into gaseous xenon, where they produce proportional scintillation. The proportional scintillation from the extracted electrons serves to internally amplify the WIMP signal; even a single extracted electron is detectable. Credible dark matter searches can proceed with electron extraction efficiency (EEE) lower than 100%. However, electrons systematically left at the liquid/gas boundary are a concern. Possible effects include spontaneous single or multi-electron proportional scintillation signals in the gas, or charging of the liquid/gas interface or detector materials. Understanding EEE is consequently a serious concern for this class of rare event search detectors. Previous EEE measurements have mostly been relative, not absolute, assuming efficiency plateaus at 100%. I will present an absolute EEE measurement with a small liquid/gas xenon TPC test bed located at Lawrence Berkeley National Laboratory.

  18. Why to compare absolute numbers of mitochondria.

    PubMed

    Schmitt, Sabine; Schulz, Sabine; Schropp, Eva-Maria; Eberhagen, Carola; Simmons, Alisha; Beisker, Wolfgang; Aichler, Michaela; Zischka, Hans

    2014-11-01

    Prompted by pronounced structural differences between rat liver and rat hepatocellular carcinoma mitochondria, we suspected these mitochondrial populations to differ massively in their molecular composition. Aiming to reveal these mitochondrial differences, we came across the issue on how to normalize such comparisons and decided to focus on the absolute number of mitochondria. To this end, fluorescently stained mitochondria were quantified by flow cytometry. For rat liver mitochondria, this approach resulted in mitochondrial protein contents comparable to earlier reports using alternative methods. We determined similar protein contents for rat liver, heart and kidney mitochondria. In contrast, however, lower protein contents were determined for rat brain mitochondria and for mitochondria from the rat hepatocellular carcinoma cell line McA 7777. This result challenges mitochondrial comparisons that rely on equal protein amounts as a typical normalization method. Exemplarily, we therefore compared the activity and susceptibility toward inhibition of complex II of rat liver and hepatocellular carcinoma mitochondria and obtained significant discrepancies by either normalizing to protein amount or to absolute mitochondrial number. Importantly, the latter normalization, in contrast to the former, demonstrated a lower complex II activity and higher susceptibility toward inhibition in hepatocellular carcinoma mitochondria compared to liver mitochondria. These findings demonstrate that solely normalizing to protein amount may obscure essential molecular differences between mitochondrial populations.

  19. Absolute Proper Motions of Southern Globular Clusters

    NASA Astrophysics Data System (ADS)

    Dinescu, D. I.; Girard, T. M.; van Altena, W. F.

    1996-05-01

    Our program involves the determination of absolute proper motions with respect to galaxies for a sample of globular clusters situated in the southern sky. The plates cover a 6(deg) x 6(deg) area and are taken with the 51-cm double astrograph at Cesco Observatory in El Leoncito, Argentina. We have developed special methods to deal with the modelling error of the plate transformation and we correct for magnitude equation using the cluster stars. This careful astrometric treatment leads to accuracies of from 0.5 to 1.0 mas/yr for the absolute proper motion of each cluster, depending primarily on the number of measurable cluster stars which in turn is related to the cluster's distance. Space velocities are then derived which, in association with metallicities, provide key information for the formation scenario of the Galaxy, i.e. accretion and/or dissipational collapse. Here we present results for NGC 1851, NGC 6752, NGC 6584, NGC 6362 and NGC 288.

  20. Relational versus absolute representation in categorization.

    PubMed

    Edwards, Darren J; Pothos, Emmanuel M; Perlman, Amotz

    2012-01-01

    This study explores relational-like and absolute-like representations in categorization. Although there is much evidence that categorization processes can involve information about both the particular physical properties of studied instances and abstract (relational) properties, there has been little work on the factors that lead to one kind of representation as opposed to the other. We tested 370 participants in 6 experiments, in which participants had to classify new items into predefined artificial categories. In 4 experiments, we observed a predominantly relational-like mode of classification, and in 2 experiments we observed a shift toward an absolute-like mode of classification. These results suggest 3 factors that promote a relational-like mode of classification: fewer items per group, more training groups, and the presence of a time delay. Overall, we propose that less information about the distributional properties of a category or weaker memory traces for the category exemplars (induced, e.g., by having smaller categories or a time delay) can encourage relational-like categorization.

  1. Transient absolute robustness in stochastic biochemical networks.

    PubMed

    Enciso, German A

    2016-08-01

    Absolute robustness allows biochemical networks to sustain a consistent steady-state output in the face of protein concentration variability from cell to cell. This property is structural and can be determined from the topology of the network alone regardless of rate parameters. An important question regarding these systems is the effect of discrete biochemical noise in the dynamical behaviour. In this paper, a variable freezing technique is developed to show that under mild hypotheses the corresponding stochastic system has a transiently robust behaviour. Specifically, after finite time the distribution of the output approximates a Poisson distribution, centred around the deterministic mean. The approximation becomes increasingly accurate, and it holds for increasingly long finite times, as the total protein concentrations grow to infinity. In particular, the stochastic system retains a transient, absolutely robust behaviour corresponding to the deterministic case. This result contrasts with the long-term dynamics of the stochastic system, which eventually must undergo an extinction event that eliminates robustness and is completely different from the deterministic dynamics. The transiently robust behaviour may be sufficient to carry out many forms of robust signal transduction and cellular decision-making in cellular organisms. PMID:27581485

  2. A Conceptual Approach to Absolute Value Equations and Inequalities

    ERIC Educational Resources Information Center

    Ellis, Mark W.; Bryson, Janet L.

    2011-01-01

    The absolute value learning objective in high school mathematics requires students to solve far more complex absolute value equations and inequalities. When absolute value problems become more complex, students often do not have sufficient conceptual understanding to make any sense of what is happening mathematically. The authors suggest that the…

  3. Using, Seeing, Feeling, and Doing Absolute Value for Deeper Understanding

    ERIC Educational Resources Information Center

    Ponce, Gregorio A.

    2008-01-01

    Using sticky notes and number lines, a hands-on activity is shared that anchors initial student thinking about absolute value. The initial point of reference should help students successfully evaluate numeric problems involving absolute value. They should also be able to solve absolute value equations and inequalities that are typically found in…

  4. Effect of distance-related heterogeneity on population size estimates from point counts

    USGS Publications Warehouse

    Efford, Murray G.; Dawson, Deanna K.

    2009-01-01

    Point counts are used widely to index bird populations. Variation in the proportion of birds counted is a known source of error, and for robust inference it has been advocated that counts be converted to estimates of absolute population size. We used simulation to assess nine methods for the conduct and analysis of point counts when the data included distance-related heterogeneity of individual detection probability. Distance from the observer is a ubiquitous source of heterogeneity, because nearby birds are more easily detected than distant ones. Several recent methods (dependent double-observer, time of first detection, time of detection, independent multiple-observer, and repeated counts) do not account for distance-related heterogeneity, at least in their simpler forms. We assessed bias in estimates of population size by simulating counts with fixed radius w over four time intervals (occasions). Detection probability per occasion was modeled as a half-normal function of distance with scale parameter sigma and intercept g(0) = 1.0. Bias varied with sigma/w; values of sigma inferred from published studies were often 50% for a 100-m fixed-radius count. More critically, the bias of adjusted counts sometimes varied more than that of unadjusted counts, and inference from adjusted counts would be less robust. The problem was not solved by using mixture models or including distance as a covariate. Conventional distance sampling performed well in simulations, but its assumptions are difficult to meet in the field. We conclude that no existing method allows effective estimation of population size from point counts.

  5. Bayesian Kernel Mixtures for Counts

    PubMed Central

    Canale, Antonio; Dunson, David B.

    2011-01-01

    Although Bayesian nonparametric mixture models for continuous data are well developed, there is a limited literature on related approaches for count data. A common strategy is to use a mixture of Poissons, which unfortunately is quite restrictive in not accounting for distributions having variance less than the mean. Other approaches include mixing multinomials, which requires finite support, and using a Dirichlet process prior with a Poisson base measure, which does not allow smooth deviations from the Poisson. As a broad class of alternative models, we propose to use nonparametric mixtures of rounded continuous kernels. An efficient Gibbs sampler is developed for posterior computation, and a simulation study is performed to assess performance. Focusing on the rounded Gaussian case, we generalize the modeling framework to account for multivariate count data, joint modeling with continuous and categorical variables, and other complications. The methods are illustrated through applications to a developmental toxicity study and marketing data. This article has supplementary material online. PMID:22523437

  6. Bayesian Kernel Mixtures for Counts.

    PubMed

    Canale, Antonio; Dunson, David B

    2011-12-01

    Although Bayesian nonparametric mixture models for continuous data are well developed, there is a limited literature on related approaches for count data. A common strategy is to use a mixture of Poissons, which unfortunately is quite restrictive in not accounting for distributions having variance less than the mean. Other approaches include mixing multinomials, which requires finite support, and using a Dirichlet process prior with a Poisson base measure, which does not allow smooth deviations from the Poisson. As a broad class of alternative models, we propose to use nonparametric mixtures of rounded continuous kernels. An efficient Gibbs sampler is developed for posterior computation, and a simulation study is performed to assess performance. Focusing on the rounded Gaussian case, we generalize the modeling framework to account for multivariate count data, joint modeling with continuous and categorical variables, and other complications. The methods are illustrated through applications to a developmental toxicity study and marketing data. This article has supplementary material online. PMID:22523437

  7. Approximate Counting of Graphical Realizations

    PubMed Central

    2015-01-01

    In 1999 Kannan, Tetali and Vempala proposed a MCMC method to uniformly sample all possible realizations of a given graphical degree sequence and conjectured its rapidly mixing nature. Recently their conjecture was proved affirmative for regular graphs (by Cooper, Dyer and Greenhill, 2007), for regular directed graphs (by Greenhill, 2011) and for half-regular bipartite graphs (by Miklós, Erdős and Soukup, 2013). Several heuristics on counting the number of possible realizations exist (via sampling processes), and while they work well in practice, so far no approximation guarantees exist for such an approach. This paper is the first to develop a method for counting realizations with provable approximation guarantee. In fact, we solve a slightly more general problem; besides the graphical degree sequence a small set of forbidden edges is also given. We show that for the general problem (which contains the Greenhill problem and the Miklós, Erdős and Soukup problem as special cases) the derived MCMC process is rapidly mixing. Further, we show that this new problem is self-reducible therefore it provides a fully polynomial randomized approximation scheme (a.k.a. FPRAS) for counting of all realizations. PMID:26161994

  8. Use of Absolute and Comparative Performance Feedback in Absolute and Comparative Judgments and Decisions

    ERIC Educational Resources Information Center

    Moore, Don A.; Klein, William M. P.

    2008-01-01

    Which matters more--beliefs about absolute ability or ability relative to others? This study set out to compare the effects of such beliefs on satisfaction with performance, self-evaluations, and bets on future performance. In Experiment 1, undergraduate participants were told they had answered 20% correct, 80% correct, or were not given their…

  9. Inhibition of lung metastasis by chemokine CCL17-mediated in vivo silencing of genes in CCR4+ Tregs.

    PubMed

    Biragyn, Arya; Bodogai, Monica; Olkhanud, Purevdorj B; Denny-Brown, Sinan R; Puri, Nitin; Ayukawa, Koichi; Kanegasaki, Shiro; Hogaboam, Cory M; Wejksza, Katarzyna; Lee-Chang, Catalina

    2013-05-01

    Despite significant attractiveness of antisense oligonucleotide/RNAi technology, its clinical application has been precluded by a lack of methods for targeted delivery and transduction of primary immune cells in vivo. Here, we devised a chemokine CCL17-based strategy (TARC-arp) that transiently silences expression of genes in immune cells by delivering inhibitory oligonucleotides through their chemokine receptors. In modeling studies using mice with established 4T1.2 breast cancer, we show that IL10 produced by CCR4 cells, in particular FoxP3 regulatory T cells (Tregs), plays an important role in lung metastasis. As such, TARC-arp-mediated silencing of IL10 or FoxP3 in CCR4 Tregs is sufficient to block lung metastasis. Thus, we provide a simple solution that circumvents the problems of RNAi use in vivo, indicating that a disease outcome can be successfully controlled by delivering inhibitory oligonucleotides with chemokines to inactivate a selective subset of immune cells. PMID:23603860

  10. The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation

    PubMed Central

    Kabat, Agnieszka M; Moghaddam, Amin E; Pearson, Claire F; Laing, Adam; Abeler-Dörner, Lucie; Forman, Simon P; Grencis, Richard K; Sattentau, Quentin; Simon, Anna Katharina; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4+ T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3+ Treg cells. Specific ablation of Atg16l1 in Foxp3+ Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders. DOI: http://dx.doi.org/10.7554/eLife.12444.001 PMID:26910010

  11. An alternative calibration method for counting P-32 reactor monitors

    SciTech Connect

    Quirk, T.J.; Vehar, D.W.

    2011-07-01

    Radioactivation of sulfur is a common technique used to measure fast neutron fluences in test and research reactors. Elemental sulfur can be pressed into pellets and used as monitors. The {sup 32}S(n, p) {sup 32}P reaction has a practical threshold of about 3 MeV and its cross section and associated uncertainties are well characterized [1]. The product {sup 32P} emits a beta particle with a maximum energy of 1710 keV [2]. This energetic beta particle allows pellets to be counted intact. ASTM Standard Test Method for Measuring Reaction Rates and Fast-Neutron Fluences by Radioactivation of Sulfur-32 (E265) [3] details a method of calibration for counting systems and subsequent analysis of results. This method requires irradiation of sulfur monitors in a fast-neutron field whose spectrum and intensity are well known. The resultant decay-corrected count rate is then correlated to the known fast neutron fluence. The Radiation Metrology Laboratory (RML) at Sandia has traditionally performed calibration irradiations of sulfur pellets using the {sup 252}Cf spontaneous fission neutron source at the National Inst. of Standards and Technology (NIST) [4] as a transfer standard. However, decay has reduced the intensity of NIST's source; thus lowering the practical upper limits of available fluence. As of May 2010, neutron emission rates have decayed to approximately 3 e8 n/s. In practice, this degradation of capabilities precludes calibrations at the highest fluence levels produced at test reactors and limits the useful range of count rates that can be measured. Furthermore, the reduced availability of replacement {sup 252}Cf threatens the long-term viability of the NIST {sup 252}Cf facility for sulfur pellet calibrations. In lieu of correlating count rate to neutron fluence in a reference field the total quantity of {sup 32}P produced in a pellet can be determined by absolute counting methods. This offers an attractive alternative to extended {sup 252}Cf exposures because it

  12. Matrine improves cognitive impairment and modulates the balance of Th17/Treg cytokines in a rat model of Aβ1-42-induced Alzheimer's disease

    PubMed Central

    Zhang, Yanfeng; Liu, Meifeng; Sun, Hongri

    2016-01-01

    Matrine (MAT) has been reported for its anti-inflammatory and neuroprotective effects. However, little is known about its effects on Th17/Treg cytokines and cognitive impairment in Alzheimer's disease (AD). In the present study, we injected Aβ1-42 to the hippocampus of the rat to induce AD. Three groups of the AD rats were treated with MAT (25, 100 or 200 mg/kg/day, respectively) by intraperitoneal injection for 5 weeks. Levels of Th17 cell cytokines [interleukin (IL)-17A and IL-23] and regulatory T (Treg) cell cytokines [transforming growth factor β (TGF-β) and IL-35] in homogenates of the brain cortex and hippocampus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expressions of Th17 cell specific transcription factor RORγt and Treg cell specific transcription factor Foxp3 in the brain cortex and hippocampus were quantified by real-time RT-PCR. Learning and memory ability of the rats were evaluated by Morris water maze test and novel object recognition test. ELISA detections showed the AD rats had increased levels of IL-17A and IL-23 as well as decreased levels of TGF-β and IL-35. Matrine (100 and 200 mg/kg/day) significantly reversed the alternations of Th17/Treg cytokines induced by Aβ1-42 injection, decreased RORγt mRNA expression, increased Foxp3 mRNA expression and improved the learning and memory ability in the AD rats. The findings demonstrated that the AD rats had imbalance of Th17/Treg cytokines in the brain. MAT could dose-dependently restore the balance of Th17/Treg cytokines and attenuate the cognitive impairment in AD rats. PMID:26862304

  13. Investigation on effects of the nourishing kidney and eliminating toxicity decoction on immunological imbalance of Th1, Th17 and Treg in HBV transgenic mice

    PubMed Central

    Liu, Ya-Min; Xu, Qiu-Ying; Chen, Jun-Xian; Chen, Song; Peng, Hao-Jun; Zeng, Zheng-Lun; Feng, Zhi-Yu; Shen, Qiang

    2015-01-01

    Objective: To study the immune mechanism of nourishing kidney and eliminating toxicity decoction (NKETD) on Chronic Hepatitis B (CHB), we detected the serum concentrations of IFN-γ (the characteristic cytokine of Th1), IL-17A (the characteristic cytokine of Th17) and the quantitative proportion of CD+ 4CD+ 25 foxp3 Treg to CD+ 4 Treg in HBV transgenic mice. Methods: The HBV transgenic mice were randomly divided into six groups: high-dose group, middle-dose group, low-dose group, lamivudine group, model control group and normal mice control group. The serum concentrations of IFN-γ and IL-17A in mice were measured by ELISA method and the ratio of CD+ 4CD+ 25 foxp3 Treg to CD+ 4 Treg was detected by Flow Cytometry Method (FCM). Results: The decoction could increase the serum concentration of IFN-γ and decrease that of IL-17A in HBV transgenic mice. The higher the dose was, the more significantly the concentration of IFN-γ increased. And high-dose decoction could decrease the serum concentration of IL-17A in HBV transgenic mice significantly and continuously while middle-dose and low-dose decoction had no significant effects. However, there wasn’t statistically significant variation on the ratio of CD+ 4CD+ 25 foxp3 Treg to CD+ 4 Treg in HBV transgenic mice. Conclusion: The decoction could treat CHB by regulating the immune function by promoting the generation of Th1 and/or enhancing its function while inhibiting Th17. The immune regulation by decoction had more significant effects than lamivudine. PMID:26221211

  14. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR. PMID:26640276

  15. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR.

  16. Absolute radiometric calibration of the CCRS SAR

    NASA Astrophysics Data System (ADS)

    Ulander, Lars M. H.; Hawkins, Robert K.; Livingstone, Charles E.; Lukowski, Tom I.

    1991-11-01

    Determining the radar scattering coefficients from SAR (synthetic aperture radar) image data requires absolute radiometric calibration of the SAR system. The authors describe an internal calibration methodology for the airborne Canada Centre for Remote Sensing (CCRS) SAR system, based on radar theory, a detailed model of the radar system, and measurements of system parameters. The methodology is verified by analyzing external calibration data acquired over a 6-month period in 1988 by the C-band radar using HH polarization. The results indicate that the overall error is +/- 0.8 dB (1-sigma) for incidence angles +/- 20 deg from antenna boresight. The dominant error contributions are due to the antenna radome and uncertainties in the elevation angle relative to the antenna boresight.

  17. Absolute measurements of fast neutrons using yttrium

    SciTech Connect

    Roshan, M. V.; Springham, S. V.; Rawat, R. S.; Lee, P.; Krishnan, M.

    2010-08-15

    Yttrium is presented as an absolute neutron detector for pulsed neutron sources. It has high sensitivity for detecting fast neutrons. Yttrium has the property of generating a monoenergetic secondary radiation in the form of a 909 keV gamma-ray caused by inelastic neutron interaction. It was calibrated numerically using MCNPX and does not need periodic recalibration. The total yttrium efficiency for detecting 2.45 MeV neutrons was determined to be f{sub n}{approx}4.1x10{sup -4} with an uncertainty of about 0.27%. The yttrium detector was employed in the NX2 plasma focus experiments and showed the neutron yield of the order of 10{sup 8} neutrons per discharge.

  18. Absolute geostrophic currents in global tropical oceans

    NASA Astrophysics Data System (ADS)

    Yang, Lina; Yuan, Dongliang

    2016-11-01

    A set of absolute geostrophic current (AGC) data for the period January 2004 to December 2012 are calculated using the P-vector method based on monthly gridded Argo profiles in the world tropical oceans. The AGCs agree well with altimeter geostrophic currents, Ocean Surface Current Analysis-Real time currents, and moored current-meter measurements at 10-m depth, based on which the classical Sverdrup circulation theory is evaluated. Calculations have shown that errors of wind stress calculation, AGC transport, and depth ranges of vertical integration cannot explain non-Sverdrup transport, which is mainly in the subtropical western ocean basins and equatorial currents near the Equator in each ocean basin (except the North Indian Ocean, where the circulation is dominated by monsoons). The identified non-Sverdrup transport is thereby robust and attributed to the joint effect of baroclinicity and relief of the bottom (JEBAR) and mesoscale eddy nonlinearity.

  19. Absolute Measurement of Electron Cloud Density

    SciTech Connect

    Covo, M K; Molvik, A W; Cohen, R H; Friedman, A; Seidl, P A; Logan, G; Bieniosek, F; Baca, D; Vay, J; Orlando, E; Vujic, J L

    2007-06-21

    Beam interaction with background gas and walls produces ubiquitous clouds of stray electrons that frequently limit the performance of particle accelerator and storage rings. Counterintuitively we obtained the electron cloud accumulation by measuring the expelled ions that are originated from the beam-background gas interaction, rather than by measuring electrons that reach the walls. The kinetic ion energy measured with a retarding field analyzer (RFA) maps the depressed beam space-charge potential and provides the dynamic electron cloud density. Clearing electrode current measurements give the static electron cloud background that complements and corroborates with the RFA measurements, providing an absolute measurement of electron cloud density during a 5 {micro}s duration beam pulse in a drift region of the magnetic transport section of the High-Current Experiment (HCX) at LBNL.

  20. Micron Accurate Absolute Ranging System: Range Extension

    NASA Technical Reports Server (NTRS)

    Smalley, Larry L.; Smith, Kely L.

    1999-01-01

    The purpose of this research is to investigate Fresnel diffraction as a means of obtaining absolute distance measurements with micron or greater accuracy. It is believed that such a system would prove useful to the Next Generation Space Telescope (NGST) as a non-intrusive, non-contact measuring system for use with secondary concentrator station-keeping systems. The present research attempts to validate past experiments and develop ways to apply the phenomena of Fresnel diffraction to micron accurate measurement. This report discusses past research on the phenomena, and the basis of the use Fresnel diffraction distance metrology. The apparatus used in the recent investigations, experimental procedures used, preliminary results are discussed in detail. Continued research and equipment requirements on the extension of the effective range of the Fresnel diffraction systems is also described.

  1. Absolute calibration of remote sensing instruments

    NASA Astrophysics Data System (ADS)

    Biggar, S. F.; Bruegge, C. J.; Capron, B. A.; Castle, K. R.; Dinguirard, M. C.; Holm, R. G.; Lingg, L. J.; Mao, Y.; Palmer, J. M.; Phillips, A. L.

    1985-12-01

    Source-based and detector-based methods for the absolute radiometric calibration of a broadband field radiometer are described. Using such a radiometer, calibrated by both methods, the calibration of the integrating sphere used in the preflight calibration of the Thematic Mapper was redetermined. The results are presented. The in-flight calibration of space remote sensing instruments is discussed. A method which uses the results of ground-based reflectance and atmospheric measurements as input to a radiative transfer code to predict the radiance at the instrument is described. A calibrated, helicopter-mounted radiometer is used to determine the radiance levels at intermediate altitudes to check the code predictions. Results of such measurements for the calibration of the Thematic Mapper on Landsat 5 and an analysis that shows the value of such measurements are described.

  2. Swarm's Absolute Scalar Magnetometer metrological performances

    NASA Astrophysics Data System (ADS)

    Leger, J.; Fratter, I.; Bertrand, F.; Jager, T.; Morales, S.

    2012-12-01

    The Absolute Scalar Magnetometer (ASM) has been developed for the ESA Earth Observation Swarm mission, planned for launch in November 2012. As its Overhauser magnetometers forerunners flown on Oersted and Champ satellites, it will deliver high resolution scalar measurements for the in-flight calibration of the Vector Field Magnetometer manufactured by the Danish Technical University. Latest results of the ground tests carried out to fully characterize all parameters that may affect its accuracy, both at instrument and satellite level, will be presented. In addition to its baseline function, the ASM can be operated either at a much higher sampling rate (burst mode at 250 Hz) or in a dual mode where it also delivers vector field measurements as a by-product. The calibration procedure and the relevant vector performances will be discussed.

  3. MAGSAT: Vector magnetometer absolute sensor alignment determination

    NASA Technical Reports Server (NTRS)

    Acuna, M. H.

    1981-01-01

    A procedure is described for accurately determining the absolute alignment of the magnetic axes of a triaxial magnetometer sensor with respect to an external, fixed, reference coordinate system. The method does not require that the magnetic field vector orientation, as generated by a triaxial calibration coil system, be known to better than a few degrees from its true position, and minimizes the number of positions through which a sensor assembly must be rotated to obtain a solution. Computer simulations show that accuracies of better than 0.4 seconds of arc can be achieved under typical test conditions associated with existing magnetic test facilities. The basic approach is similar in nature to that presented by McPherron and Snare (1978) except that only three sensor positions are required and the system of equations to be solved is considerably simplified. Applications of the method to the case of the MAGSAT Vector Magnetometer are presented and the problems encountered discussed.

  4. Providing reference standards and metrology for the few photon-photon counting community

    NASA Astrophysics Data System (ADS)

    Beaumont, Andrew R.; Cheung, Jessica Y.; Chunnilall, Christopher J.; Ireland, Jane; White, Malcolm G.

    2009-10-01

    The main drivers for developing few-photon metrological techniques are the rapidly progressing field of quantum information processing, which requires the development of high-efficiency photon-counting detectors, and the wider use of photon-counting technology in biology, medical physics and nuclear physics. This paper will focus on the provision of standards for the few photon community and the development of techniques for the characterisation of photon-counting detectors. At the high-power end, microwatts, we are developing a low-power absolute radiometer as a primary standard that will be used to provide traceability over a much broader spectral range. At the few photon-photon-counting level we are developing a conventional calibration technique, which is traceable to the primary standard through a reference trap detector. This method can be used in both analogue and photon-counting modes and provides a convenient route for providing customer calibration at few-photon levels across the optical spectrum. At the photon-counting/single-photon level we are developing a technique based on correlated photons. These are produced via parametric downconversion and can be used to measure directly the detection efficiency of photon-counting detectors. A cross-validation of the correlated photon and conventional technique is reported. Finally we discuss this work in the context of an EU project, that is aimed at establishing the route towards the re-definition of the candela, the SI unit for optical radiation.

  5. White blood cell count - series (image)

    MedlinePlus

    ... measures two components: the total number of WBC's (leukocytes), and the differential count. The differential count measures the percentages of each type of leukocyte present. WBC's are composed of granulocytes (neutrophils, eosinophils, ...

  6. Reviving common standards in point-count surveys for broad inference across studies

    USGS Publications Warehouse

    Matsuoka, Steven M.; Mahon, C. Lisa; Handel, Colleen M.; Solymos, Peter; Bayne, Erin M.; Fontaine, Patricia C.; Ralph, C.J.

    2014-01-01

    We revisit the common standards recommended by Ralph et al. (1993, 1995a) for conducting point-count surveys to assess the relative abundance of landbirds breeding in North America. The standards originated from discussions among ornithologists in 1991 and were developed so that point-count survey data could be broadly compared and jointly analyzed by national data centers with the goals of monitoring populations and managing habitat. Twenty years later, we revisit these standards because (1) they have not been universally followed and (2) new methods allow estimation of absolute abundance from point counts, but these methods generally require data beyond the original standards to account for imperfect detection. Lack of standardization and the complications it introduces for analysis become apparent from aggregated data. For example, only 3% of 196,000 point counts conducted during the period 1992-2011 across Alaska and Canada followed the standards recommended for the count period and count radius. Ten-minute, unlimited-count-radius surveys increased the number of birds detected by >300% over 3-minute, 50-m-radius surveys. This effect size, which could be eliminated by standardized sampling, was ≥10 times the published effect sizes of observers, time of day, and date of the surveys. We suggest that the recommendations by Ralph et al. (1995a) continue to form the common standards when conducting point counts. This protocol is inexpensive and easy to follow but still allows the surveys to be adjusted for detection probabilities. Investigators might optionally collect additional information so that they can analyze their data with more flexible forms of removal and time-of-detection models, distance sampling, multiple-observer methods, repeated counts, or combinations of these methods. Maintaining the common standards as a base protocol, even as these study-specific modifications are added, will maximize the value of point-count data, allowing compilation and

  7. Count rate limitations in pulsed accelerator fields

    SciTech Connect

    Justus, Alan L

    2010-12-15

    This paper discusses various concepts involved in the counting losses of pulse-counting health physics instrumentation when used within the pulsed radiation environments of typical accelerator fields, in order to pre-establish appropriate limitations in use. Discussed are the 'narrow' pulse and the 'wide' pulse cases, the special effect of neutron moderating assemblies, and the effect of pulse microstructure on the counting losses of the pulse-counting instrumentation. Examples are provided which highlight the various concepts and limitations.

  8. Race-specific WBC and neutrophil count reference intervals.

    PubMed

    Lim, E-M; Cembrowski, George; Cembrowski, M; Clarke, G

    2010-12-01

    Healthy African Americans are known to have reduced white blood cell counts (WBC) and absolute neutrophil counts (ANC) compared with European Americans, with little agreement about the levels in reference intervals. The objective is to establish race-specific reference intervals for WBC and ANC using US National Health and Nutrition Examination Survey (NHANES) of 2000-2003. A total of 14,184 civilian noninstitutionalized US citizens participated in NHANES 2000-2003 had complete blood count, red cell distribution width, platelet count and automated WBC differential determined on a Coulter MAXM. The exclusion criteria were used: ferritin <12 ng/ml, pregnancy, body mass index >30, diastolic blood pressure >100 mm Hg, creatinine >2.5 mg/dl, glucose >126 mg/dl. Data were separated into six sex/race categories: female non-Hispanic white, non-Hispanic black (NHBF)], Mexican American; male non-Hispanic white, non-Hispanic black (NHBM), Mexican American and two age groupings (12-18 and >18 years). NHB 2.5-97.5 percentile WBC and (ANC) limits follow (units: × 10⁹ /l): NHBM, ages 12-18: 3.2-9.3 (1.0-6.2); NHBF, ages 12-18: 3.7-10.1 (1.2-6.6); adult NHBM: 3.1-9.9 (1.3-6.6); adult NHBF: 3.4-11 (1.4-7.5). NHB limits are significantly lower than the NHW and MA limits. In most US healthcare organizations, insufficient agreement exists because of large differences in reference intervals for different ethnicities. In areas with peoples of African descent (>10--20%), race-specific WBC and ANC reference intervals must be provided for proper diagnosis and clinical research.

  9. SPERM COUNT DISTRIBUTIONS IN FERTILE MEN

    EPA Science Inventory

    Sperm concentration and count are often used as indicators of environmental impacts on male reproductive health. Existing clinical databases may be biased towards subfertile men with low sperm counts and less is known about expected sperm count distributions in cohorts of fertil...

  10. Count-doubling time safety circuit

    DOEpatents

    Rusch, Gordon K.; Keefe, Donald J.; McDowell, William P.

    1981-01-01

    There is provided a nuclear reactor count-factor-increase time monitoring circuit which includes a pulse-type neutron detector, and means for counting the number of detected pulses during specific time periods. Counts are compared and the comparison is utilized to develop a reactor scram signal, if necessary.

  11. DC KIDS COUNT e-Databook Indicators

    ERIC Educational Resources Information Center

    DC Action for Children, 2012

    2012-01-01

    This report presents indicators that are included in DC Action for Children's 2012 KIDS COUNT e-databook, their definitions and sources and the rationale for their selection. The indicators for DC KIDS COUNT represent a mix of traditional KIDS COUNT indicators of child well-being, such as the number of children living in poverty, and indicators of…

  12. Monte Carlo Simulation of Counting Experiments.

    ERIC Educational Resources Information Center

    Ogden, Philip M.

    A computer program to perform a Monte Carlo simulation of counting experiments was written. The program was based on a mathematical derivation which started with counts in a time interval. The time interval was subdivided to form a binomial distribution with no two counts in the same subinterval. Then the number of subintervals was extended to…

  13. Airborne dust particle counting techniques.

    PubMed

    Sharma, S G; Prasad, B D

    2006-03-01

    The paper briefly describes an electro-optical system for counting of dust particles, which is based on the scattering phenomena. Utilizing the scattering of light by various size particles present in the environment, various particle counting techniques have been developed in order to measure the scattered intensity of light. Light scatters in all directions but much more in the so-called near forward direction 17( composite function) off axis, at 163( composite function) from the light source in the visible range. On the basis of two techniques, the right angle and forward angle scattering, opto-mechanical systems have been developed which measure scattered intensity and particulate matter. The forward scattering Nephelometer is more sensitive and therefore is more suitable for pollution monitoring than the right angle scattering Nephelometer. Whereas the right angle scattering Nephelometer has the utility in extremely low concentration in ppb level owing to the excellent light trap efficiency in comparison to forward scattering Nephelometer. In this paper measurement techniques and measurement results associated with design and development of a real time particle analyser are also discussed.

  14. Verification of 235U mass content in nuclear fuel plates by an absolute method

    NASA Astrophysics Data System (ADS)

    El-Gammal, W.

    2007-01-01

    Nuclear Safeguards is referred to a verification System by which a State can control all nuclear materials (NM) and nuclear activities under its authority. An effective and efficient Safeguards System must include a system of measurements with capabilities sufficient to verify such NM. Measurements of NM using absolute methods could eliminate the dependency on NM Standards, which are necessary for other relative or semi-absolute methods. In this work, an absolute method has been investigated to verify the 235U mass content in nuclear fuel plates of Material Testing Reactor (MTR) type. The most intense gamma-ray signature at 185.7 keV emitted after α-decay of the 235U nuclei was employed in the method. The measuring system (an HPGe-spectrometer) was mathematically calibrated for efficiency using the general Monte Carlo transport code MCNP-4B. The calibration results and the measured net count rate were used to estimate the 235U mass content in fuel plates at different detector-to-fuel plate distances. Two sets of fuel plates, containing natural and low enriched uranium, were measured at the Fuel Fabrication Facility. Average accuracies for the estimated 235U masses of about 2.62% and 0.3% are obtained for the fuel plates containing natural and low enriched uranium; respectively, with a precision of about 3%.

  15. On the absolute alignment of GONG images

    NASA Astrophysics Data System (ADS)

    Toner, C. G.

    2001-01-01

    In order to combine data from the six instruments in the GONG network the alignment of all of the images must be known to a fairly high precision (~0°.1 for GONG Classic and ~0°.01 for GONG+). The relative orientation is obtained using the angular cross-correlation method described by (Toner & Harvey, 1998). To obtain the absolute orientation the Project periodically records a day of drift scans, where the image of the Sun is allowed to drift across the CCD repeatedly throughout the day. These data are then analyzed to deduce the direction of Terrestrial East-West as a function of hour angle (i.e., time) for that instrument. The transit of Mercury on Nov. 15, 1999, which was recorded by three of the GONG instruments, provided an independent check on the current alignment procedures. Here we present a comparison of the alignment of GONG images as deduced from both drift scans and the Mercury transit for two GONG sites: Tucson (GONG+ camera) and Mauna Loa (GONG Classic camera). The agreement is within ~0°.01 for both cameras, however, the scatter is substantially larger for GONG Classic: ~0°.03 compared to ~0°.01 for GONG+.

  16. Climate Absolute Radiance and Refractivity Observatory (CLARREO)

    NASA Technical Reports Server (NTRS)

    Leckey, John P.

    2015-01-01

    The Climate Absolute Radiance and Refractivity Observatory (CLARREO) is a mission, led and developed by NASA, that will measure a variety of climate variables with an unprecedented accuracy to quantify and attribute climate change. CLARREO consists of three separate instruments: an infrared (IR) spectrometer, a reflected solar (RS) spectrometer, and a radio occultation (RO) instrument. The mission will contain orbiting radiometers with sufficient accuracy, including on orbit verification, to calibrate other space-based instrumentation, increasing their respective accuracy by as much as an order of magnitude. The IR spectrometer is a Fourier Transform spectrometer (FTS) working in the 5 to 50 microns wavelength region with a goal of 0.1 K (k = 3) accuracy. The FTS will achieve this accuracy using phase change cells to verify thermistor accuracy and heated halos to verify blackbody emissivity, both on orbit. The RS spectrometer will measure the reflectance of the atmosphere in the 0.32 to 2.3 microns wavelength region with an accuracy of 0.3% (k = 2). The status of the instrumentation packages and potential mission options will be presented.

  17. Absolute flux measurements for swift atoms

    NASA Technical Reports Server (NTRS)

    Fink, M.; Kohl, D. A.; Keto, J. W.; Antoniewicz, P.

    1987-01-01

    While a torsion balance in vacuum can easily measure the momentum transfer from a gas beam impinging on a surface attached to the balance, this measurement depends on the accommodation coefficients of the atoms with the surface and the distribution of the recoil. A torsion balance is described for making absolute flux measurements independent of recoil effects. The torsion balance is a conventional taut suspension wire design and the Young modulus of the wire determines the relationship between the displacement and the applied torque. A compensating magnetic field is applied to maintain zero displacement and provide critical damping. The unique feature is to couple the impinging gas beam to the torsion balance via a Wood's horn, i.e., a thin wall tube with a gradual 90 deg bend. Just as light is trapped in a Wood's horn by specular reflection from the curved surfaces, the gas beam diffuses through the tube. Instead of trapping the beam, the end of the tube is open so that the atoms exit the tube at 90 deg to their original direction. Therefore, all of the forward momentum of the gas beam is transferred to the torsion balance independent of the angle of reflection from the surfaces inside the tube.

  18. Gyrokinetic Statistical Absolute Equilibrium and Turbulence

    SciTech Connect

    Jian-Zhou Zhu and Gregory W. Hammett

    2011-01-10

    A paradigm based on the absolute equilibrium of Galerkin-truncated inviscid systems to aid in understanding turbulence [T.-D. Lee, "On some statistical properties of hydrodynamical and magnetohydrodynamical fields," Q. Appl. Math. 10, 69 (1952)] is taken to study gyrokinetic plasma turbulence: A finite set of Fourier modes of the collisionless gyrokinetic equations are kept and the statistical equilibria are calculated; possible implications for plasma turbulence in various situations are discussed. For the case of two spatial and one velocity dimension, in the calculation with discretization also of velocity v with N grid points (where N + 1 quantities are conserved, corresponding to an energy invariant and N entropy-related invariants), the negative temperature states, corresponding to the condensation of the generalized energy into the lowest modes, are found. This indicates a generic feature of inverse energy cascade. Comparisons are made with some classical results, such as those of Charney-Hasegawa-Mima in the cold-ion limit. There is a universal shape for statistical equilibrium of gyrokinetics in three spatial and two velocity dimensions with just one conserved quantity. Possible physical relevance to turbulence, such as ITG zonal flows, and to a critical balance hypothesis are also discussed.

  19. Automatic cell counting with ImageJ.

    PubMed

    Grishagin, Ivan V

    2015-03-15

    Cell counting is an important routine procedure. However, to date there is no comprehensive, easy to use, and inexpensive solution for routine cell counting, and this procedure usually needs to be performed manually. Here, we report a complete solution for automatic cell counting in which a conventional light microscope is equipped with a web camera to obtain images of a suspension of mammalian cells in a hemocytometer assembly. Based on the ImageJ toolbox, we devised two algorithms to automatically count these cells. This approach is approximately 10 times faster and yields more reliable and consistent results compared with manual counting.

  20. Wavefunction collapse through backaction of counting weakly interacting photons

    NASA Astrophysics Data System (ADS)

    Harrell, L. E.

    2016-03-01

    We apply the formalism of quantum measurement theory to the idealized measurement of the position of a particle with an optical interferometer, finding that the backaction of counting entangled photons systematically collapses the particle's wavefunction toward a narrow Gaussian wavepacket at the location xest determined by the measurement without appeal to environmental decoherence or other spontaneous collapse mechanism. Further, the variance in the particle's position, as calculated from the post-measurement wavefunction, agrees precisely with shot-noise limited uncertainty of the measured xest. Both the identification of the absolute square of the particle's initial wavefunction as the probability density for xest and the de Broglie hypothesis emerge as consequences of interpreting the intensity of the optical field as proportional to the probability of detecting a photon. Linear momentum information that is encoded in the particle's initial wavefunction survives the measurement, and the pre-measurement expectation values are preserved in the ensemble average.

  1. Issues in Absolute Spectral Radiometric Calibration: Intercomparison of Eight Sources

    NASA Technical Reports Server (NTRS)

    Goetz, Alexander F. H.; Kindel, Bruce; Pilewskie, Peter

    1998-01-01

    The application of atmospheric models to AVIRIS and other spectral imaging data to derive surface reflectance requires that the sensor output be calibrated to absolute radiance. Uncertainties in absolute calibration are to be expected, and claims of 92% accuracy have been published. Measurements of accurate surface albedos and cloud absorption to be used in radiative balance calculations depend critically on knowing the absolute spectral-radiometric response of the sensor. The Earth Observing System project is implementing a rigorous program of absolute radiometric calibration for all optical sensors. Since a number of imaging instruments that provide output in terms of absolute radiance are calibrated at different sites, it is important to determine the errors that can be expected among calibration sites. Another question exists about the errors in the absolute knowledge of the exoatmospheric spectral solar irradiance.

  2. IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity.

    PubMed

    Fabrizi, Marta; Marchetti, Valentina; Mavilio, Maria; Marino, Arianna; Casagrande, Viviana; Cavalera, Michele; Moreno-Navarrete, Josè Maria; Mezza, Teresa; Sorice, Gian Pio; Fiorentino, Loredana; Menghini, Rossella; Lauro, Renato; Monteleone, Giovanni; Giaccari, Andrea; Fernandez Real, José Manuel; Federici, Massimo

    2014-06-01

    Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since interleukin (IL)-21 plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Treg differentiation/activity, we hypothesized that it could play a role in obesity-induced insulin resistance. We found IL-21 and IL-21R mRNA expression upregulated in adipose tissue of high-fat diet (HFD) wild-type (WT) mice and in stromal vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly, a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (KO) mice compared with WT animals fed both normal diet and HFD. In a context of diet-induced obesity, IL-21 KO mice, compared with WT animals, exhibited lower body weight, improved insulin sensitivity, and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by a higher induction of interferon regulatory factor 4 (IRF4), a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Treg activity, developing and maintaining adipose tissue inflammation in the obesity state.

  3. Bacterial counts associated with recycled newspaper bedding.

    PubMed

    Hogan, J S; Smith, K L; Todhunter, D A; Schoenberger, P S

    1990-07-01

    Bacterial counts associated with recycled newspaper, wood shavings, and pelleted corn cobs used as bedding for lactating dairy cows were compared. Chopped newspaper and pelleted corn cobs had similar gram-negative bacterial, coliform, and streptococcal bedding counts. Staphylococcal counts in pelleted corn cobs were greater than in chopped newspaper. Conversely, gram-negative bacterial, coliform, and staphylococcal counts in chopped newspaper were greater than in wood shavings. Coliform and streptococcal counts did not differ between chopped newspaper and wood shavings bedding materials. Teat swab counts from cows bedded on pelleted corn cobs were greater than those from cows bedded on chopped newspaper for gram-negative bacterial, coliform, Klebsiella species, and staphylococci. Streptococcal teat swab counts did not differ between cows bedded on chopped newspaper and pelleted corn cobs. Cows bedded on chopped newspaper and wood shavings had similar gram-negative bacterial, coliform, and Klebsiella species teat swab counts. Streptococcal and staphylococcal teat swab counts were greater from cows bedded on chopped newspaper than those from cows bedded on wood shavings. Teat swab and bedding counts were correlated. In general, bacterial counts in bedding suggest no advantage in using chopped newspaper over pelleted corn cobs or wood shavings in reducing exposure of teats to environmental mastitis pathogens. PMID:2229587

  4. Kids Count in Delaware, Families Count in Delaware: Fact Book, 2003.

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Kids Count in Delaware.

    This Kids Count Fact Book is combined with the Families Count Fact Book to provide information on statewide trends affecting children and families in Delaware. The Kids Count and Families Count indicators have been combined into four new categories: health and health behaviors, educational involvement and achievement, family environment and…

  5. Antifungal activity of tuberose absolute and some of its constituents.

    PubMed

    Nidiry, Eugene Sebastian J; Babu, C S Bujji

    2005-05-01

    The antifungal activity of the absolute of tuberose (Polianthes tuberosa ) and some of its constituents were evaluated against the mycelial growth of Colletotrichum gloeosporioides on potato-dextrose-agar medium. Tuberose absolute showed only mild activity at a concentration of 500 mg/L. However, three constituents present in the absolute, namely geraniol, indole and methyl anthranilate exhibited significant activity showing total inhibition of the mycelial growth at this concentration.

  6. Houttuynia cordata Thunb reverses oxaliplatin-induced neuropathic pain in rat by regulating Th17/Treg balance.

    PubMed

    Wan, Cheng-Fu; Zheng, Li-Li; Liu, Yan; Yu, Xue

    2016-01-01

    Oxaliplatin is a widely used anti-advanced colorectal cancer drug, while it could induce neuropathy. Houttuynia cordata Thunb (HCT) has a wide range of biological activities, such as anti-inflammation, anti-cancer, and immune regulation. In the present study, we investigated the effect of HCT on oxaliplatin-induced neuropathy in rat models. HCT (1000 mg/kg/day) significantly decreased the number of withdrawal responses and the withdrawal latency in oxaliplatin-treated rats. HCT could down-regulated the serum levels of Interleukin-6 (IL-6) and macrophage inflammatory protein1-α (MIP-1α) in oxaliplatin-treated rats. Th17/Treg balance was reversed by HCT in oxaliplatin-treated rats by regulating PI3K/Akt/mTOR signaling pathway. The present results suggest that HCT is useful as a therapeutic drug for oxaliplatin-induced neuropathic pain. PMID:27186286

  7. Houttuynia cordata Thunb reverses oxaliplatin-induced neuropathic pain in rat by regulating Th17/Treg balance

    PubMed Central

    Wan, Cheng-Fu; Zheng, Li-Li; Liu, Yan; Yu, Xue

    2016-01-01

    Oxaliplatin is a widely used anti-advanced colorectal cancer drug, while it could induce neuropathy. Houttuynia cordata Thunb (HCT) has a wide range of biological activities, such as anti-inflammation, anti-cancer, and immune regulation. In the present study, we investigated the effect of HCT on oxaliplatin-induced neuropathy in rat models. HCT (1000 mg/kg/day) significantly decreased the number of withdrawal responses and the withdrawal latency in oxaliplatin-treated rats. HCT could down-regulated the serum levels of Interleukin-6 (IL-6) and macrophage inflammatory protein1-α (MIP-1α) in oxaliplatin-treated rats. Th17/Treg balance was reversed by HCT in oxaliplatin-treated rats by regulating PI3K/Akt/mTOR signaling pathway. The present results suggest that HCT is useful as a therapeutic drug for oxaliplatin-induced neuropathic pain. PMID:27186286

  8. The absolute disparity anomaly and the mechanism of relative disparities.

    PubMed

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne

    2016-06-01

    There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1).

  9. The absolute disparity anomaly and the mechanism of relative disparities

    PubMed Central

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne

    2016-01-01

    There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1). PMID:27248566

  10. γc-signaling cytokines induce a regulatory T cell (Treg) phenotype in malignant CD4+ T lymphocytes

    PubMed Central

    Kasprzycka, M; Zhang, Q; Witkiewicz, A; Marzec, M; Potoczek, M; Liu, X; Wang, HY; Milone, M; Basu, S; Mauger, J; Choi, JK; Abrams, T; Hou, S; Rook, AH; Vonderheid, E; Woetmann, A; Odum, N; Wasik, MA

    2008-01-01

    Here we demonstrate that malignant mature CD4+ T lymphocytes derived from cutaneous T-cell lymphomas (CTCL) variably display some aspects of the Tregulatory (Treg) phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T-cell lymphoproliferative disorders expressed CD25 and TGF-β, the expression of FOXP3 and, to a lesser degree, IL-10 was restricted to two CTCL cell lines that are dependent on exogeneous IL-2. IL-2, IL-15 and IL-21, all of which signals through receptors containing the common γ (γc) chain, induced expression of IL-10 in the IL-2-dependent cell lines as well as primary leukemic CTCL cells. However, only IL-2 and IL-15, but not IL-21, induced expression of FOXP3. The IL-2-triggered induction of IL-10 and FOXP3 expression occurred by signaling through STAT3 and STAT5, respectively. Immunohistochemical analysis of the CTCL tissues revealed that FOXP3-expressing cells were common among the CD7-negative enlarged atypical and small lymphocytes at the early, skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate that the Treg cell features are induced in CTCL T cells by γc signaling cytokines such as IL-2 and do not represent a fully pre-determined, constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4+ T cells become exposed. PMID:18684941

  11. Rejection of metastatic 4T1 breast cancer by attenuation of Treg cells in combination with immune stimulation.

    PubMed

    Chen, Li; Huang, Tian-Gui; Meseck, Marcia; Mandeli, John; Fallon, John; Woo, Savio L C

    2007-12-01

    4T1 breast carcinoma is a highly malignant and poorly immunogenic murine tumor model that resembles advanced breast cancer in humans, and is refractory to most immune stimulation-based treatments. We hypothesize that the ineffectiveness of immune stimulatory treatment is mediated by the suppressive effects of CD4(+)CD25(+) regulatory T (Treg) cells, which can be attenuated by engaging the glucocorticoid-induced tumor necrosis factor receptor family-related protein with its natural ligand (GITRL); further, combination treatment with existing immune stimulation regimens will augment anti-tumor immunity and eradicate metastatic 4T1 tumors in mice.A soluble homodimeric form of mouse GITRL (mIg-mGITRLs) was molecularly constructed and used to treat orthotopic 4T1 tumors established in immune-competent, syngeneic Balb/c mice. When applied in combination with adenovirus-mediated intratumoral murine granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-12 (IL-12) gene delivery plus systemic 4-1BB activation, mIg-mGITRLs attenuated the immune-suppressive function of splenic Treg cells, which led to elevated interferon-gamma (IFN-gamma) production, tumor-specific cytolytic T-cell activities, tumor rejection and long-term survival in 65% of the animals without apparent toxicities. The results demonstrate that addition of mIg-mGITRLs to an immune-stimulatory treatment regimen significantly improved long-term survival without apparent toxicity, and could potentially be clinically translated into an effective and safe treatment modality for metastatic breast cancer in patients. PMID:17968355

  12. Counting hypermaps by Egorychev's method

    NASA Astrophysics Data System (ADS)

    Mednykh, Alexander; Nedela, Roman

    2016-09-01

    The aim of this paper is to find explicit formulae for the number of rooted hypermaps with a given number of darts on an orientable surface of genus g≤ 3. Such formulae were obtained earlier for g=0 and g=1 by Walsh and Arquès respectively. We first employ the Egorychev's method of counting combinatorial sums to obtain a new version of the Arquès formula for genus g=1. Then we apply the same approach to get new results for genus g=2,3. We could do it due to recent results by Giorgetti, Walsh, and Kazarian, Zograf who derived two different, but equivalent, forms of the generating functions for the number of hypermaps of genus two and three.

  13. Counting solutions from finite samplings.

    PubMed

    Huang, Haiping; Zhou, Haijun

    2012-02-01

    We formulate the solution counting problem within the framework of the inverse Ising problem and use fast belief propagation equations to estimate the entropy whose value provides an estimate of the true one. We test this idea on both diluted models [random 2-SAT (2-satisfiability) and 3-SAT problems] and a fully connected model (binary perceptron), and show that when the constraint density is small, this estimate can be very close to the true value. The information stored by the salamander retina under the natural movie stimuli can also be estimated, and our result is consistent with that obtained by the Monte Carlo method. Of particular significance is that the sizes of other metastable states for this real neuronal network are predicted. PMID:22463290

  14. Counting solutions from finite samplings

    NASA Astrophysics Data System (ADS)

    Huang, Haiping; Zhou, Haijun

    2012-02-01

    We formulate the solution counting problem within the framework of the inverse Ising problem and use fast belief propagation equations to estimate the entropy whose value provides an estimate of the true one. We test this idea on both diluted models [random 2-SAT (2-satisfiability) and 3-SAT problems] and a fully connected model (binary perceptron), and show that when the constraint density is small, this estimate can be very close to the true value. The information stored by the salamander retina under the natural movie stimuli can also be estimated, and our result is consistent with that obtained by the Monte Carlo method. Of particular significance is that the sizes of other metastable states for this real neuronal network are predicted.

  15. Low Background Counting At SNOLAB

    SciTech Connect

    Lawson, Ian; Cleveland, Bruce

    2011-04-27

    It is a continuous and ongoing effort to maintain radioactivity in materials and in the environment surrounding most underground experiments at very low levels. These low levels are required so that experiments can achieve the required detection sensitivities for the detection of low-energy neutrinos, searches for dark matter and neutrinoless double-beta decay. SNOLAB has several facilities which are used to determine these low background levels in the materials and the underground environment. This proceedings will describe the SNOLAB High Purity Germanium Detector which has been in continuous use for the past five years and give results of many of the items that have been counted over that period. Brief descriptions of SNOLAB's alpha-beta and electrostatic counters will be given, and the radon levels at SNOLAB will be discussed.

  16. Well coincidence counting and analysis

    SciTech Connect

    Lu, Ming-Shih; Teichmann, T.; Ceo, R.N.; Collins, L.L.

    1994-03-01

    In several recent papers a physical/mathematical model was developed to describe the nuclear multiplicative processes in samples containing fissile material from a general statistical viewpoint, starting with the basic underlying physical phenomena. The results of this model agreed with the established picture used in ``standard`` HLNCC (High Level Neutron Coincidence Counter) measurements, but considerably extended them, and allowed a more detailed interpretation of the underlying physical mechanisms and of the higher moments of the neutron counts. The present paper examines some recent measurements made at Y-12 (Oak Ridge) using the AWCC, in the light of this model. The results show internal consistency under a variety of conditions, and give good agreement between experiment and theory.

  17. Photon counting compressive depth mapping.

    PubMed

    Howland, Gregory A; Lum, Daniel J; Ware, Matthew R; Howell, John C

    2013-10-01

    We demonstrate a compressed sensing, photon counting lidar system based on the single-pixel camera. Our technique recovers both depth and intensity maps from a single under-sampled set of incoherent, linear projections of a scene of interest at ultra-low light levels around 0.5 picowatts. Only two-dimensional reconstructions are required to image a three-dimensional scene. We demonstrate intensity imaging and depth mapping at 256 × 256 pixel transverse resolution with acquisition times as short as 3 seconds. We also show novelty filtering, reconstructing only the difference between two instances of a scene. Finally, we acquire 32 × 32 pixel real-time video for three-dimensional object tracking at 14 frames-per-second. PMID:24104293

  18. Counting paths with Schur transitions

    NASA Astrophysics Data System (ADS)

    Díaz, Pablo; Kemp, Garreth; Véliz-Osorio, Alvaro

    2016-10-01

    In this work we explore the structure of the branching graph of the unitary group using Schur transitions. We find that these transitions suggest a new combinatorial expression for counting paths in the branching graph. This formula, which is valid for any rank of the unitary group, reproduces known asymptotic results. We proceed to establish the general validity of this expression by a formal proof. The form of this equation strongly hints towards a quantum generalization. Thus, we introduce a notion of quantum relative dimension and subject it to the appropriate consistency tests. This new quantity finds its natural environment in the context of RCFTs and fractional statistics; where the already established notion of quantum dimension has proven to be of great physical importance.

  19. Counting Electrons on Liquid Helium

    NASA Astrophysics Data System (ADS)

    Glasson, Phillip

    2004-03-01

    Electrons on liquid helium, localised in an array of quantum dots, have been proposed as condensed matter qubits [M.I.Dykman et al. Phys.Rev. B 67, 155402 (2003)]. The ground and first excited Rydberg states in the vertical potential well on the helium surface would represent |0> and |1>. This requires (a) novel electronic devices on helium using microstructured substrates, (b) excitation of Rydberg states using millimetric microwaves and (c) detection of individual electrons and their quantum states. Progress in meeting these challenges will be presented. An AC-coupled Field Effect Transistor (FET) has been made on GaAs, using free electrons on suspended liquid helium microchannels, 16 micron wide and 1.6 microns deep [P.Glasson et al, Phys.Rev.Lett. 87 176802 (2001)]. The microwave absorption to the first excited Rydberg state near 200 GHz has been measured below 1 K [E.Collin et al. Phys.Rev.Lett. 89, 245301 (2002)], where the temperature-dependent contribution to the linewidth is small. High values of the ratio of the Rabi frequency to the linewidth are obtained. Electrons are trapped on a 5 micron diameter pool of superfluid helium, above a single-electron-transistor (SET) as a detector. The pool is charged from a surface electron reservoir and we count the electrons into and out of the trap. Individual electrons can be stored, detected and counted: the next stage is quantum state detection. The prospects for qubits and quantum information processing with electrons on helium will be assessed.

  20. Absolute Plate Velocities from Seismic Anisotropy

    NASA Astrophysics Data System (ADS)

    Kreemer, Corné; Zheng, Lin; Gordon, Richard

    2015-04-01

    The orientation of seismic anisotropy inferred beneath plate interiors may provide a means to estimate the motions of the plate relative to the sub-asthenospheric mantle. Here we analyze two global sets of shear-wave splitting data, that of Kreemer [2009] and an updated and expanded data set, to estimate plate motions and to better understand the dispersion of the data, correlations in the errors, and their relation to plate speed. We also explore the effect of using geologically current plate velocities (i.e., the MORVEL set of angular velocities [DeMets et al. 2010]) compared with geodetically current plate velocities (i.e., the GSRM v1.2 angular velocities [Kreemer et al. 2014]). We demonstrate that the errors in plate motion azimuths inferred from shear-wave splitting beneath any one tectonic plate are correlated with the errors of other azimuths from the same plate. To account for these correlations, we adopt a two-tier analysis: First, find the pole of rotation and confidence limits for each plate individually. Second, solve for the best fit to these poles while constraining relative plate angular velocities to consistency with the MORVEL relative plate angular velocities. The SKS-MORVEL absolute plate angular velocities (based on the Kreemer [2009] data set) are determined from the poles from eight plates weighted proportionally to the root-mean-square velocity of each plate. SKS-MORVEL indicates that eight plates (Amur, Antarctica, Caribbean, Eurasia, Lwandle, Somalia, Sundaland, and Yangtze) have angular velocities that differ insignificantly from zero. The net rotation of the lithosphere is 0.25±0.11° Ma-1 (95% confidence limits) right-handed about 57.1°S, 68.6°E. The within-plate dispersion of seismic anisotropy for oceanic lithosphere (σ=19.2° ) differs insignificantly from that for continental lithosphere (σ=21.6° ). The between-plate dispersion, however, is significantly smaller for oceanic lithosphere (σ=7.4° ) than for continental

  1. Evaluation of the Absolute Regional Temperature Potential

    NASA Technical Reports Server (NTRS)

    Shindell, D. T.

    2012-01-01

    The Absolute Regional Temperature Potential (ARTP) is one of the few climate metrics that provides estimates of impacts at a sub-global scale. The ARTP presented here gives the time-dependent temperature response in four latitude bands (90-28degS, 28degS-28degN, 28-60degN and 60-90degN) as a function of emissions based on the forcing in those bands caused by the emissions. It is based on a large set of simulations performed with a single atmosphere-ocean climate model to derive regional forcing/response relationships. Here I evaluate the robustness of those relationships using the forcing/response portion of the ARTP to estimate regional temperature responses to the historic aerosol forcing in three independent climate models. These ARTP results are in good accord with the actual responses in those models. Nearly all ARTP estimates fall within +/-20%of the actual responses, though there are some exceptions for 90-28degS and the Arctic, and in the latter the ARTP may vary with forcing agent. However, for the tropics and the Northern Hemisphere mid-latitudes in particular, the +/-20% range appears to be roughly consistent with the 95% confidence interval. Land areas within these two bands respond 39-45% and 9-39% more than the latitude band as a whole. The ARTP, presented here in a slightly revised form, thus appears to provide a relatively robust estimate for the responses of large-scale latitude bands and land areas within those bands to inhomogeneous radiative forcing and thus potentially to emissions as well. Hence this metric could allow rapid evaluation of the effects of emissions policies at a finer scale than global metrics without requiring use of a full climate model.

  2. Absolute Radiometric Calibration of KOMPSAT-3A

    NASA Astrophysics Data System (ADS)

    Ahn, H. Y.; Shin, D. Y.; Kim, J. S.; Seo, D. C.; Choi, C. U.

    2016-06-01

    This paper presents a vicarious radiometric calibration of the Korea Multi-Purpose Satellite-3A (KOMPSAT-3A) performed by the Korea Aerospace Research Institute (KARI) and the Pukyong National University Remote Sensing Group (PKNU RSG) in 2015.The primary stages of this study are summarized as follows: (1) A field campaign to determine radiometric calibrated target fields was undertaken in Mongolia and South Korea. Surface reflectance data obtained in the campaign were input to a radiative transfer code that predicted at-sensor radiance. Through this process, equations and parameters were derived for the KOMPSAT-3A sensor to enable the conversion of calibrated DN to physical units, such as at-sensor radiance or TOA reflectance. (2) To validate the absolute calibration coefficients for the KOMPSAT-3A sensor, we performed a radiometric validation with a comparison of KOMPSAT-3A and Landsat-8 TOA reflectance using one of the six PICS (Libya 4). Correlations between top-of-atmosphere (TOA) radiances and the spectral band responses of the KOMPSAT-3A sensors at the Zuunmod, Mongolia and Goheung, South Korea sites were significant for multispectral bands. The average difference in TOA reflectance between KOMPSAT-3A and Landsat-8 image over the Libya 4, Libya site in the red-green-blue (RGB) region was under 3%, whereas in the NIR band, the TOA reflectance of KOMPSAT-3A was lower than the that of Landsat-8 due to the difference in the band passes of two sensors. The KOMPSAT-3Aensor includes a band pass near 940 nm that can be strongly absorbed by water vapor and therefore displayed low reflectance. Toovercome this, we need to undertake a detailed analysis using rescale methods, such as the spectral bandwidth adjustment factor.

  3. Orion Absolute Navigation System Progress and Challenge

    NASA Technical Reports Server (NTRS)

    Holt, Greg N.; D'Souza, Christopher

    2012-01-01

    The absolute navigation design of NASA's Orion vehicle is described. It has undergone several iterations and modifications since its inception, and continues as a work-in-progress. This paper seeks to benchmark the current state of the design and some of the rationale and analysis behind it. There are specific challenges to address when preparing a timely and effective design for the Exploration Flight Test (EFT-1), while still looking ahead and providing software extensibility for future exploration missions. The primary onboard measurements in a Near-Earth or Mid-Earth environment consist of GPS pseudo-range and delta-range, but for future explorations missions the use of star-tracker and optical navigation sources need to be considered. Discussions are presented for state size and composition, processing techniques, and consider states. A presentation is given for the processing technique using the computationally stable and robust UDU formulation with an Agee-Turner Rank-One update. This allows for computational savings when dealing with many parameters which are modeled as slowly varying Gauss-Markov processes. Preliminary analysis shows up to a 50% reduction in computation versus a more traditional formulation. Several state elements are discussed and evaluated, including position, velocity, attitude, clock bias/drift, and GPS measurement biases in addition to bias, scale factor, misalignment, and non-orthogonalities of the accelerometers and gyroscopes. Another consideration is the initialization of the EKF in various scenarios. Scenarios such as single-event upset, ground command, and cold start are discussed as are strategies for whole and partial state updates as well as covariance considerations. Strategies are given for dealing with latent measurements and high-rate propagation using multi-rate architecture. The details of the rate groups and the data ow between the elements is discussed and evaluated.

  4. Absolute determination of local tropospheric OH concentrations

    NASA Technical Reports Server (NTRS)

    Armerding, Wolfgang; Comes, Franz-Josef

    1994-01-01

    Long path absorption (LPA) according to Lambert Beer's law is a method to determine absolute concentrations of trace gases such as tropospheric OH. We have developed a LPA instrument which is based on a rapid tuning of the light source which is a frequency doubled dye laser. The laser is tuned across two or three OH absorption features around 308 nm with a scanning speed of 0.07 cm(exp -1)/microsecond and a repetition rate of 1.3 kHz. This high scanning speed greatly reduces the fluctuation of the light intensity caused by the atmosphere. To obtain the required high sensitivity the laser output power is additionally made constant and stabilized by an electro-optical modulator. The present sensitivity is of the order of a few times 10(exp 5) OH per cm(exp 3) for an acquisition time of a minute and an absorption path length of only 1200 meters so that a folding of the optical path in a multireflection cell was possible leading to a lateral dimension of the cell of a few meters. This allows local measurements to be made. Tropospheric measurements have been carried out in 1991 resulting in the determination of OH diurnal variation at specific days in late summer. Comparison with model calculations have been made. Interferences are mainly due to SO2 absorption. The problem of OH self generation in the multireflection cell is of minor extent. This could be shown by using different experimental methods. The minimum-maximum signal to noise ratio is about 8 x 10(exp -4) for a single scan. Due to the small size of the absorption cell the realization of an open air laboratory is possible in which by use of an additional UV light source or by additional fluxes of trace gases the chemistry can be changed under controlled conditions allowing kinetic studies of tropospheric photochemistry to be made in open air.

  5. Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis and control of autoimmune arthritis

    PubMed Central

    Astry, Brian; Venkatesha, Shivaprasad H.; Moudgil, Kamal D.

    2014-01-01

    The T helper (Th) cell subsets are characterized by the type of cytokines produced and the master transcription factor expressed. Th1 cells participate in cell-mediated immunity, whereas Th2 cells promote humoral immunity. Furthermore, the two subsets can control each other. Thereby, Th1-Th2 balance offered a key paradigm in understanding the induction and regulation of immune pathology in autoimmune and other diseases. However, over the past decade, Th17 cells producing interleukin-17 (IL-17) have emerged as the major pathogenic T cell subset in many pathological conditions that were previously attributed to Th1 cells. In addition, the role of CD4+CD25+ T regulatory cells (Treg) in controlling the activity of Th17 and other T cell subsets has increasingly been realized. Thereby, examination of the Th17/Treg balance in the course of autoimmune diseases has significantly advanced our understanding of the pathogenesis of these disorders. The differentiation of Th17 and Treg cells from naïve T cells is inter-related and controlled in part by the cytokine milieu. For example, transforming growth factor β (TGFβ) is required for Treg induction, whereas the same cytokine in the presence of IL-6 (or IL-1) promotes the differentiation of Th17. Furthermore, IL-23 plays a role in the maintenance of Th17. Accordingly, novel therapeutic approaches are being developed to target IL-23/IL-17 as well as to modulate the Th17/Treg balance in favor of immune regulation to control autoimmunity. PMID:25595306

  6. Natural T Regulatory Cells (n Treg) in the Peripheral Blood of Healthy Subjects and Subjects with Chronic Periodontitis – A Pilot Study

    PubMed Central

    Sabarish, Ram; Lavu, Vamsi

    2016-01-01

    Introduction The T cells play a central role in the aetiopathogenesis of periodontal disease. Natural T regulatory cells (nTreg) are the key stone immunoregulatory elements having an anergic phenotype and play an important role in the suppression of exaggerated immune responses thereby maintaining homeostasis. There are increasing evidences for the role of nTreg in the periodontal disease pathogenesis. Aim To identify the proportion of natural T regulatory cells in the peripheral blood of periodontally healthy subjects and subjects with chronic periodontitis. Materials and Methods A total of 15 subjects (7 with healthy gingiva and 8 with chronic periodontitis) were recruited for this pilot study. Baseline periodontal parameters were recorded and 5 ml of peripheral blood was collected. The samples from both the groups were analysed for the relative proportion of nTreg (identified by the expression CD45RB+CD4+CD25+FOXP3+) using flow cytometry. Results The mean percentages of the CD45RB+CD4+CD25+ cells expressing FOXP3 in control and chronic periodontitis group were found to be 14.75±5.04 and 43.13±11.17 respectively. The mean proportion of nTreg were compared between the control and chronic periodontitis sample using Mann-Whitney Test and was found to be statistically significant with (p<0.001). Conclusion A higher proportion of nTreg in the peripheral blood sample of chronic periodontitis subjects were observed as compared to that of healthy individuals. PMID:27134998

  7. The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal

    PubMed Central

    Liu, Yongzhe; Qiu, Lan; Wang, Yanxun; Aimurola, Halimulati; Zhao, Yuyue; Li, Shan; Xu, Zuojun

    2016-01-01

    Objectives Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients. Methods Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission. Results The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed. Conclusions An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The

  8. Self-Digitization Microfluidic Chip for Absolute Quantification of mRNA in Single Cells

    PubMed Central

    2015-01-01

    Quantification of mRNA in single cells provides direct insight into how intercellular heterogeneity plays a role in disease progression and outcomes. Quantitative polymerase chain reaction (qPCR), the current gold standard for evaluating gene expression, is insufficient for providing absolute measurement of single-cell mRNA transcript abundance. Challenges include difficulties in handling small sample volumes and the high variability in measurements. Microfluidic digital PCR provides far better sensitivity for minute quantities of genetic material, but the typical format of this assay does not allow for counting of the absolute number of mRNA transcripts samples taken from single cells. Furthermore, a large fraction of the sample is often lost during sample handling in microfluidic digital PCR. Here, we report the absolute quantification of single-cell mRNA transcripts by digital, one-step reverse transcription PCR in a simple microfluidic array device called the self-digitization (SD) chip. By performing the reverse transcription step in digitized volumes, we find that the assay exhibits a linear signal across a wide range of total RNA concentrations and agrees well with standard curve qPCR. The SD chip is found to digitize a high percentage (86.7%) of the sample for single-cell experiments. Moreover, quantification of transferrin receptor mRNA in single cells agrees well with single-molecule fluorescence in situ hybridization experiments. The SD platform for absolute quantification of single-cell mRNA can be optimized for other genes and may be useful as an independent control method for the validation of mRNA quantification techniques. PMID:25390242

  9. Self-digitization microfluidic chip for absolute quantification of mRNA in single cells.

    PubMed

    Thompson, Alison M; Gansen, Alexander; Paguirigan, Amy L; Kreutz, Jason E; Radich, Jerald P; Chiu, Daniel T

    2014-12-16

    Quantification of mRNA in single cells provides direct insight into how intercellular heterogeneity plays a role in disease progression and outcomes. Quantitative polymerase chain reaction (qPCR), the current gold standard for evaluating gene expression, is insufficient for providing absolute measurement of single-cell mRNA transcript abundance. Challenges include difficulties in handling small sample volumes and the high variability in measurements. Microfluidic digital PCR provides far better sensitivity for minute quantities of genetic material, but the typical format of this assay does not allow for counting of the absolute number of mRNA transcripts samples taken from single cells. Furthermore, a large fraction of the sample is often lost during sample handling in microfluidic digital PCR. Here, we report the absolute quantification of single-cell mRNA transcripts by digital, one-step reverse transcription PCR in a simple microfluidic array device called the self-digitization (SD) chip. By performing the reverse transcription step in digitized volumes, we find that the assay exhibits a linear signal across a wide range of total RNA concentrations and agrees well with standard curve qPCR. The SD chip is found to digitize a high percentage (86.7%) of the sample for single-cell experiments. Moreover, quantification of transferrin receptor mRNA in single cells agrees well with single-molecule fluorescence in situ hybridization experiments. The SD platform for absolute quantification of single-cell mRNA can be optimized for other genes and may be useful as an independent control method for the validation of mRNA quantification techniques.

  10. Avian leucocyte counting using the hemocytometer

    USGS Publications Warehouse

    Dein, F.J.; Wilson, A.; Fischer, D.; Langenberg, P.

    1994-01-01

    Automated methods for counting leucocytes in avian blood are not available because of the presence of nucleated erythrocytes and thrombocytes. Therefore, total white blood cell counts are performed by hand using a hemocytometer. The Natt and Herrick and the Unopette methods are the most common stain and diluent preparations for this procedure. Replicate hemocytometer counts using these two methods were performed on blood from four birds of different species. Cells present in each square of the hemocytometer were counted. Counting cells in the corner, side, or center hemocytometer squares produced statistically equivalent results; counting four squares per chamber provided a result similar to that obtained by counting nine squares; and the Unopette method was more precise for hemocytometer counting than was the Natt and Herrick method. The Unopette method is easier to learn and perform but is an indirect process, utilizing the differential count from a stained smear. The Natt and Herrick method is a direct total count, but cell identification is more difficult.

  11. Reference ranges and sources of variability of CD4 counts in HIV-seronegative women and men.

    PubMed Central

    Maini, M K; Gilson, R J; Chavda, N; Gill, S; Fakoya, A; Ross, E J; Phillips, A N; Weller, I V

    1996-01-01

    BACKGROUND: CD4 lymphocyte counts are used to monitor immune status in HIV disease. An understanding of the variability of CD4 counts which occurs in the absence of HIV infection is essential to their interpretation. The sources and degree of such variability have not been extensively studied. OBJECTIVES: To establish reference ranges for CD4 counts in HIV-seronegative women and heterosexual men attending a genitourinary medicine (GUM) clinic, and to identify possible differences according to gender and cigarette smoking and, in women, any effect of the menstrual cycle, oral contraceptive use and cigarette smoking. DESIGN: Female and heterosexual male patients attending a GUM clinic and requesting an HIV-antibody test were recruited prospectively. Results from an earlier study of CD4 counts in homosexual men were available for comparison. METHODS: Lymphocyte subpopulation analysis on whole blood by flow cytometry. RESULTS: The absolute CD4 count and percentage of CD4 cells (CD4%) were significantly higher in women (n = 195) than heterosexual men (n = 91) [difference between the means 111 x 106/1 (95% CI 41, 180) and 3.1% (1.30, 4.88)]. The absolute CD4 count and CD4% were also significantly higher in smokers (n = 143) than non-smokers (n = 140) [difference 143 (79, 207) and 2.1% (0.43, 3.81)]. Reference ranges for absolute CD4 counts (geometric mean +/- 2SD) were calculated on log transformed data as follows; female smokers 490-1610, female non-smokers 430-1350, heterosexual male smokers 380-1600, heterosexual male non-smokers 330-1280. Among other variables examined, combined oral contraceptive pill use was associated with a trend towards a lower absolute CD4 count. Changes were seen in CD4% with the menstrual cycle. CD4 counts and CD4% did not differ significantly between heterosexual men and homosexual men (n = 45). CONCLUSION: There is a significant gender and smoking effect on CD4 counts. The effects of oral contraceptive use and the menstrual cycle warrant

  12. Mid-infrared absolute spectral responsivity scale based on an absolute cryogenic radiometer and an optical parametric oscillator laser

    NASA Astrophysics Data System (ADS)

    Zhao, Kun; Shi, Xueshun; Chen, Haidong; Liu, Yulong; Liu, Changming; Chen, Kunfeng; Li, Ligong; Gan, Haiyong; Ma, Chong

    2016-06-01

    We are reporting on a laser-based absolute spectral responsivity scale in the mid-infrared spectral range. By using a mid-infrared tunable optical parametric oscillator as the laser source, the absolute responsivity scale has been established by calibrating thin-film thermopile detectors against an absolute cryogenic radiometer. The thin-film thermopile detectors can be then used as transfer standard detectors. The extended uncertainty of the absolute spectral responsivity measurement has been analyzed to be 0.58%–0.68% (k  =  2).

  13. Mid-infrared absolute spectral responsivity scale based on an absolute cryogenic radiometer and an optical parametric oscillator laser

    NASA Astrophysics Data System (ADS)

    Zhao, Kun; Shi, Xueshun; Chen, Haidong; Liu, Yulong; Liu, Changming; Chen, Kunfeng; Li, Ligong; Gan, Haiyong; Ma, Chong

    2016-06-01

    We are reporting on a laser-based absolute spectral responsivity scale in the mid-infrared spectral range. By using a mid-infrared tunable optical parametric oscillator as the laser source, the absolute responsivity scale has been established by calibrating thin-film thermopile detectors against an absolute cryogenic radiometer. The thin-film thermopile detectors can be then used as transfer standard detectors. The extended uncertainty of the absolute spectral responsivity measurement has been analyzed to be 0.58%-0.68% (k  =  2).

  14. Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25-FoxP3- T cells.

    PubMed

    Centuori, Sara M; Trad, Malika; LaCasse, Collin J; Alizadeh, Darya; Larmonier, Claire B; Hanke, Neale T; Kartchner, Jessica; Janikashvili, Nona; Bonnotte, Bernard; Larmonier, Nicolas; Katsanis, Emmanuel

    2012-11-01

    MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined. Previous reports have suggested that MDSC may contribute to Treg induction in cancer. Herein, we provide evidence that tumor-induced gr-MDSCs, endowed with the potential of suppressing conventional T Lc, surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs. Furthermore, gr-MDSCs impede the proliferation of nTregs without, however, affecting FoxP3 expression. Suppression of iTreg differentiation from naïve CD4(+) cells by gr-MDSC occurs early in the polarization process, requires inhibition of early T cell activation, and depends on ROS and IDO but does not require arginase 1, iNOS, NO, cystine/cysteine depletion, PD-1 and PD-L1 signaling, or COX-2. These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs.

  15. Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25−FoxP3− T cells

    PubMed Central

    Centuori, Sara M.; Trad, Malika; LaCasse, Collin J.; Alizadeh, Darya; Larmonier, Claire B.; Hanke, Neale T.; Kartchner, Jessica; Janikashvili, Nona; Bonnotte, Bernard; Larmonier, Nicolas; Katsanis, Emmanuel

    2012-01-01

    MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined. Previous reports have suggested that MDSC may contribute to Treg induction in cancer. Herein, we provide evidence that tumor-induced gr-MDSCs, endowed with the potential of suppressing conventional T Lc, surprisingly impair TGF-β1-mediated generation of CD4+CD25+FoxP3+ iTregs. Furthermore, gr-MDSCs impede the proliferation of nTregs without, however, affecting FoxP3 expression. Suppression of iTreg differentiation from naïve CD4+ cells by gr-MDSC occurs early in the polarization process, requires inhibition of early T cell activation, and depends on ROS and IDO but does not require arginase 1, iNOS, NO, cystine/cysteine depletion, PD-1 and PD-L1 signaling, or COX-2. These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs. PMID:22891289

  16. Novalis' Poetic Uncertainty: A "Bildung" with the Absolute

    ERIC Educational Resources Information Center

    Mika, Carl

    2016-01-01

    Novalis, the Early German Romantic poet and philosopher, had at the core of his work a mysterious depiction of the "absolute." The absolute is Novalis' name for a substance that defies precise knowledge yet calls for a tentative and sensitive speculation. How one asserts a truth, represents an object, and sets about encountering things…

  17. Absolute Pitch in Infant Auditory Learning: Evidence for Developmental Reorganization.

    ERIC Educational Resources Information Center

    Saffran, Jenny R.; Griepentrog, Gregory J.

    2001-01-01

    Two experiments examined 8-month-olds' use of absolute and relative pitch cues in a tone-sequence statistical learning task. Results suggest that, given unsegmented stimuli that do not conform to rules of musical composition, infants are more likely to track patterns of absolute pitches than of relative pitches. A third experiment found that adult…

  18. Supplementary and Enrichment Series: Absolute Value. Teachers' Commentary. SP-25.

    ERIC Educational Resources Information Center

    Bridgess, M. Philbrick, Ed.

    This is one in a series of manuals for teachers using SMSG high school supplementary materials. The pamphlet includes commentaries on the sections of the student's booklet, answers to the exercises, and sample test questions. Topics covered include addition and multiplication in terms of absolute value, graphs of absolute value in the Cartesian…

  19. Supplementary and Enrichment Series: Absolute Value. SP-24.

    ERIC Educational Resources Information Center

    Bridgess, M. Philbrick, Ed.

    This is one in a series of SMSG supplementary and enrichment pamphlets for high school students. This series is designed to make material for the study of topics of special interest to students readily accessible in classroom quantity. Topics covered include absolute value, addition and multiplication in terms of absolute value, graphs of absolute…

  20. Absolute dimensions of unevolved O type close binaries

    SciTech Connect

    Doom, C.; de Loore, C.

    1984-03-15

    A method is presented to derive the absolute dimensions of early-type detached binaries by combining the observed parameters with results of evolutionary computations. The method is used to obtain the absolute dimensions of nine close binaries. We find that most systems have an initial masss ratio near 1.

  1. Absolute Humidity and the Seasonality of Influenza (Invited)

    NASA Astrophysics Data System (ADS)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

    2010-12-01

    Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

  2. Determination of Absolute Zero Using a Computer-Based Laboratory

    ERIC Educational Resources Information Center

    Amrani, D.

    2007-01-01

    We present a simple computer-based laboratory experiment for evaluating absolute zero in degrees Celsius, which can be performed in college and undergraduate physical sciences laboratory courses. With a computer, absolute zero apparatus can help demonstrators or students to observe the relationship between temperature and pressure and use…

  3. Absolute radiometric calibration of advanced remote sensing systems

    NASA Technical Reports Server (NTRS)

    Slater, P. N.

    1982-01-01

    The distinction between the uses of relative and absolute spectroradiometric calibration of remote sensing systems is discussed. The advantages of detector-based absolute calibration are described, and the categories of relative and absolute system calibrations are listed. The limitations and problems associated with three common methods used for the absolute calibration of remote sensing systems are addressed. Two methods are proposed for the in-flight absolute calibration of advanced multispectral linear array systems. One makes use of a sun-illuminated panel in front of the sensor, the radiance of which is monitored by a spectrally flat pyroelectric radiometer. The other uses a large, uniform, high-radiance reference ground surface. The ground and atmospheric measurements required as input to a radiative transfer program to predict the radiance level at the entrance pupil of the orbital sensor are discussed, and the ground instrumentation is described.

  4. Smoking, allergy, and the differential white blood cell count.

    PubMed Central

    Taylor, R G; Gross, E; Joyce, H; Holland, F; Pride, N B

    1985-01-01

    Dutch workers have proposed that people with asthma and those smokers who develop chronic airflow obstruction share a common allergic constitution. To study whether smoking itself is associated with indicators of allergy, we have examined 237 men aged 51-61 years (120 smokers, 73 ex-smokers, and 44 non-smokers) who were recruited to a long term study of lung function in 1974, at which time men with a clinical diagnosis of asthma were excluded. Smokers, ex-smokers, and non-smokers did not differ in personal or family history of allergic disease, but the prevalence of positive responses to skinprick tests was greater in ex-smokers (59%) than in the other two groups (33% and 34%). In men with negative responses to skinprick tests total serum IgE was greater in smokers (log10 mean 1.41 IU/ml) and in ex-smokers (log10 mean 1.53 IU/ml) than in non-smokers (log10 mean 1.12 IU/ml). In men with positive skin test responses serum IgE was similar in the three groups (log10 mean ranging from 1.68 to 1.78 IU/ml). Geometric mean total white cell counts in the peripheral blood were higher in smokers (7.34 X 10(9)/l) than in non-smokers (5.82 X 10(9)/l); the value in ex-smokers (6.16 X 10(9)/l) was intermediate. Absolute blood eosinophil counts were increased in smokers disproportionately to the increase in total white cell count. Thus smoking is associated with small increases in some markers of allergy. These changes are probably acquired after the onset of smoking but sequential studies are required to amplify these cross sectional observations. Smokers whose skin test responses are positive appear more likely to give up smoking. PMID:3969651

  5. Peripheral Blood Lymphocyte Subset Counts in Pre-menopausal Women with Iron-Deficiency Anaemia

    PubMed Central

    Reza Keramati, Mohammad; Sadeghian, Mohammad Hadi; Ayatollahi, Hossein; Mahmoudi, Mahmoud; Khajedaluea, Mohammad; Tavasolian, Houman; Borzouei, Anahita

    2011-01-01

    Background: Iron-deficiency anaemia (IDA) is a major worldwide public health problem. Children and women of reproductive age are especially vulnerable to IDA, and it has been reported that these patients are more prone to infection. This study was done to evaluate alteration of lymphocyte subgroups in IDA. Methods: In this prospective study, we investigated lymphocyte subsets in pre-menopausal women with iron-deficiency anaemia; 50 normal subjects and 50 IDA (hypochromic microcytic) cases were enrolled. Experimental and control anticoagulated blood samples were evaluated using flow cytometry to determine the absolute and relative numbers of various lymphocyte subgroups. Finally, the results of the patient and control groups were compared. Results: Mean (SD) absolute counts of lymphocytes, CD3+ cells, CD3+/CD4+ subsets (T helper) and CD3+/CD8+ subsets (T cytotoxic) in the patient group were 2.08 (0.65) x 109/L, 1.53 (0.53) x 109/L, 0.87 (0.28) x 109/L, and 0.51 (0.24) x 109/L, respectively. The results showed significant differences between case and control groups in mean absolute counts of lymphocytes (P = 0.014), T lymphocytes (P = 0.009), helper T cells (P = 0.004), and cytotoxic T cells (P = 0.043). Conclusion: This study showed that absolute counts of peripheral blood T lymphocytes as a marker of cell-mediated immunity may be decreased in pre-menopausal women with iron-deficiency anaemia, and that these patients may be more prone to infection. PMID:22135572

  6. Low Background Counting at LBNL

    DOE PAGES

    Smith, A. R.; Thomas, K. J.; Norman, E. B.; Chan, Y. D.; Lesko, K. T.; Hurley, D. L.

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K)more » or common cosmogenic/anthropogenic products, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.« less

  7. Low Background Counting at LBNL

    SciTech Connect

    Smith, A. R.; Thomas, K. J.; Norman, E. B.; Chan, Y. D.; Lesko, K. T.; Hurley, D. L.

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  8. Identification of CSF fistulas by radionuclide counting

    SciTech Connect

    Yamamoto, Y.; Kunishio, K.; Sunami, N.; Yamamoto, Y.; Satoh, T.; Suga, M.; Asari, S. )

    1990-07-01

    A radionuclide counting method, performed with the patient prone and the neck flexed, was used successfully to diagnose CSF rhinorrhea in two patients. A normal radionuclide ratio (radionuclide counts in pledget/radionuclide counts in 1-ml blood sample) was obtained in 11 normal control subjects. Significance was determined to be a ratio greater than 0.37. Use of radionuclide counting method of determining CSF rhinorrhea is recommended when other methods have failed to locate a site of leakage or when posttraumatic meningitis suggests subclinical CSF rhinorrhea.

  9. Th1-Like ICOS+ Foxp3+ Treg Cells Preferentially Express CXCR3 and Home to β-Islets during Pre-Diabetes in BDC2.5 NOD Mice.

    PubMed

    Kornete, Mara; Mason, Edward S; Girouard, Julien; Lafferty, Erin I; Qureshi, Salman; Piccirillo, Ciriaco A

    2015-01-01

    Type 1 diabetes (T1D) occurs through a breakdown of self-tolerance resulting in the autoimmune destruction of the insulin producing β-islets of the pancreas. A numerical and functional waning of CD4+ Foxp3+ regulatory T (Treg) cells, prompted by a pancreatic IL-2 deficiency, accompanies Th1 autoimmunity and T1D progression in non-obese diabetic (NOD) mice. Recently, we identified a dominant subset of intra-islet Treg cells that expresses the ICOS costimulatory receptor and promotes self-tolerance delaying the onset of T1D. ICOS co-stimulation potently enhances IL-2 induced survival and proliferation, and suppressive activity of Treg cells in situ. Here, we propose an ICOS-dependent mechanism of Treg cell homing to the β-islets during pre-diabetes in the NOD model via upregulation of the CXCR3 chemokine receptor. The islet-specific ICOS+ Treg cell subset preferentially expresses CXCR3 in the pancreatic lymph nodes (pLN) in response to Teff cell-mediated pancreatic inflammation, an expression correlating with the onset and magnitude of IFN-γ production by Teff cells in pancreatic sites. We also reveal that intra-pancreatic APC populations and insulin-producing β, but not α nor δ, islet cells secrete the CXCR3 chemokines, CXCL9, 10 and 11, and selectively promote ICOS+ CXCR3+ Treg cell chemotaxis in vitro. Strikingly, islet-derived Treg cells also produce these chemokines suggesting an auto-regulation of homing by this subset. Unlike ICOS- cells, ICOS+ Treg cells adopt a Th1-like Treg phenotype while maintaining their suppressive capacity, characterized by expression of T-bet and CXCR3 and production of IFN-γ in the draining pLNs. Finally, in vivo neutralization of IFN-γ blocked Treg cell CXCR3 upregulation evincing its role in regulating expression of this chemokine receptor by Treg cells. Thus, CXCR3-mediated trafficking of Treg cells could represent a mechanism of homeostatic immunoregulation during diabetogeneesis. PMID:25946021

  10. Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4+ CD25+ Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice

    PubMed Central

    Wang, Junhua; Vuitton, Dominique A.; Müller, Norbert; Hemphill, Andrew; Spiliotis, Markus; Blagosklonov, Oleg; Grandgirard, Denis; Leib, Stephen L.; Shalev, Itay; Levy, Gary; Lu, Xiaomei; Lin, Renyong; Wen, Hao; Gottstein, Bruno

    2015-01-01

    Background The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. Methods/Findings Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. Conclusions FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation

  11. All-Trans Retinoic Acid Promotes TGF-β-Induced Tregs via Histone Modification but Not DNA Demethylation on Foxp3 Gene Locus

    PubMed Central

    Li, Zhiyuan; Lan, Qin; Chen, Maogen; Liu, Ya; Xia, Zanxian; Wang, Julie; Han, Yuanping; Shi, Wei; Quesniaux, Valerie; Ryffel, Bernhard; Brand, David; Li, Bin; Liu, Zhongmin; Zheng, Song Guo

    2011-01-01

    Background It has been documented all-trans retinoic acid (atRA) promotes the development of TGF-β-induced CD4+Foxp3+ regulatory T cells (iTreg) that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs. Methodology/Principal Findings Addition of atRA to naïve CD4+CD25− cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS) elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered. Conclusions/Significance We have identified the cellular and molecular mechanism(s) by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation. PMID:21931768

  12. Mini-implants and miniplates generate sub-absolute and absolute anchorage

    PubMed Central

    Consolaro, Alberto

    2014-01-01

    The functional demand imposed on bone promotes changes in the spatial properties of osteocytes as well as in their extensions uniformly distributed throughout the mineralized surface. Once spatial deformation is established, osteocytes create the need for structural adaptations that result in bone formation and resorption that happen to meet the functional demands. The endosteum and the periosteum are the effectors responsible for stimulating adaptive osteocytes in the inner and outer surfaces.Changes in shape, volume and position of the jaws as a result of skeletal correction of the maxilla and mandible require anchorage to allow bone remodeling to redefine morphology, esthetics and function as a result of spatial deformation conducted by orthodontic appliances. Examining the degree of changes in shape, volume and structural relationship of areas where mini-implants and miniplates are placed allows us to classify mini-implants as devices of subabsolute anchorage and miniplates as devices of absolute anchorage. PMID:25162561

  13. 2009 KidsCount in Colorado!

    ERIC Educational Resources Information Center

    Colorado Children's Campaign, 2009

    2009-01-01

    "KidsCount in Colorado!" is an annual publication of the Colorado Children's Campaign, which provides the best available state- and county-level data to measure and track the education, health and general well-being of the state's children. KidsCount in Colorado! informs policy debates and community discussions, serving as a valuable resource for…

  14. 2008 KidsCount in Colorado!

    ERIC Educational Resources Information Center

    Colorado Children's Campaign, 2008

    2008-01-01

    "KidsCount in Colorado!" is an annual publication of the Colorado Children's Campaign, which provides the best available state- and county-level data to measure and track the education, health and general well-being of the state's children. KidsCount in Colorado! informs policy debates and community discussions, serving as a valuable resource for…

  15. 2013 Kids Count in Colorado! Community Matters

    ERIC Educational Resources Information Center

    Colorado Children's Campaign, 2013

    2013-01-01

    "Kids Count in Colorado!" is an annual publication of the Children's Campaign, providing state and county level data on child well-being factors including child health, education, and economic status. Since its first release 20 years ago, "Kids Count in Colorado!" has become the most trusted source for data and information on…

  16. Accuracy of Carbohydrate Counting in Adults.

    PubMed

    Meade, Lisa T; Rushton, Wanda E

    2016-07-01

    In Brief This study investigates carbohydrate counting accuracy in patients using insulin through a multiple daily injection regimen or continuous subcutaneous insulin infusion. The average accuracy test score for all patients was 59%. The carbohydrate test in this study can be used to emphasize the importance of carbohydrate counting to patients and to provide ongoing education. PMID:27621531

  17. Early Concepts of Number and Counting

    ERIC Educational Resources Information Center

    Box, Katherine; Scott, Paul

    2004-01-01

    Before primitive man had grasped the concept of number, the written word or even speech, he was able to count. This was important for keeping track of food supplies, sending messages, trading between villages and even keeping track of how many animals were in their herd. Counting was done in various ways, but in all cases, the underlying principle…

  18. 7 CFR 1220.625 - Counting requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.625 Counting requests. (a) The... ineligibility determinations, the requests shall be counted no later than the 14th business day following...

  19. Is It Counting, or Is It Adding?

    ERIC Educational Resources Information Center

    Eisenhardt, Sara; Fisher, Molly H.; Thomas, Jonathan; Schack, Edna O.; Tassell, Janet; Yoder, Margaret

    2014-01-01

    The Common Core State Standards for Mathematics (CCSSI 2010) expect second grade students to "fluently add and subtract within 20 using mental strategies" (2.OA.B.2). Most children begin with number word sequences and counting approximations and then develop greater skill with counting. But do all teachers really understand how this…

  20. Comb-calibrated frequency-modulated continuous-wave ladar for absolute distance measurements.

    PubMed

    Baumann, Esther; Giorgetta, Fabrizio R; Coddington, Ian; Sinclair, Laura C; Knabe, Kevin; Swann, William C; Newbury, Nathan R

    2013-06-15

    We demonstrate a comb-calibrated frequency-modulated continuous-wave laser detection and ranging (FMCW ladar) system for absolute distance measurements. The FMCW ladar uses a compact external cavity laser that is swept quasi-sinusoidally over 1 THz at a 1 kHz rate. The system simultaneously records the heterodyne FMCW ladar signal and the instantaneous laser frequency at sweep rates up to 3400 THz/s, as measured against a free-running frequency comb (femtosecond fiber laser). Demodulation of the ladar signal against the instantaneous laser frequency yields the range to the target with 1 ms update rates, bandwidth-limited 130 μm resolution and a ~100 nm accuracy that is directly linked to the counted repetition rate of the comb. The precision is <100 nm at the 1 ms update rate and reaches ~6 nm for a 100 ms average. PMID:23938965

  1. In-progress absolute radiometric inflight calibration of the LANDSAT-4 sensors

    NASA Technical Reports Server (NTRS)

    Castle, K.; Dinguirard, M.; Ezra, C. E.; Holm, R. G.; Jackson, R. J.; Kastner, C. J.; Palmer, J. M.; Savage, R.; Slater, P. N.

    1983-01-01

    An approach is described for providing periodic inflight absolute radiometric calibrations of the LANDSAT-4 sensors by reference to selected, instrumented ground areas. Results of some early ground measurements and computer simulations are presented. Selection of a suitable ground reference site, accurate measurement of the spectral reflectance of the selected area, determination of atmospheric characteristics during the morning of the sensor overpass, reduction of the measured data and their use in an appropriate atmospheric radiative transfer program, and comparison of the radiance level data with the digital counts of for the images of the selected areas are discussed. Preliminary measurements of gypsum are being made as an aid in defining the characteristics of field equipment to be constructed and calibrated for use over the White Sands Missile Range.

  2. An All Fiber White Light Interferometric Absolute Temperature Measurement System

    PubMed Central

    Kim, Jeonggon Harrison

    2008-01-01

    Recently the author of this article proposed a new signal processing algorithm for an all fiber white light interferometer. In this article, an all fiber white light interferometric absolute temperature measurement system is presented using the previously proposed signal processing algorithm. Stability and absolute temperature measurement were demonstrated. These two tests demonstrated the feasibility of absolute temperature measurement with an accuracy of 0.015 fringe and 0.0005 fringe, respectively. A hysteresis test from 373K to 873K was also presented. Finally, robustness of the sensor system towards laser diode temperature drift, AFMZI temperature drift and PZT non-linearity was demonstrated.

  3. Absolute Antenna Calibration at the US National Geodetic Survey

    NASA Astrophysics Data System (ADS)

    Mader, G. L.; Bilich, A. L.

    2012-12-01

    Geodetic GNSS applications routinely demand millimeter precision and extremely high levels of accuracy. To achieve these accuracies, measurement and instrument biases at the centimeter to millimeter level must be understood. One of these biases is the antenna phase center, the apparent point of signal reception for a GNSS antenna. It has been well established that phase center patterns differ between antenna models and manufacturers; additional research suggests that the addition of a radome or the choice of antenna mount can significantly alter those a priori phase center patterns. For the more demanding GNSS positioning applications and especially in cases of mixed-antenna networks, it is all the more important to know antenna phase center variations as a function of both elevation and azimuth in the antenna reference frame and incorporate these models into analysis software. Determination of antenna phase center behavior is known as "antenna calibration". Since 1994, NGS has computed relative antenna calibrations for more than 350 antennas. In recent years, the geodetic community has moved to absolute calibrations - the IGS adopted absolute antenna phase center calibrations in 2006 for use in their orbit and clock products, and NGS's CORS group began using absolute antenna calibration upon the release of the new CORS coordinates in IGS08 epoch 2005.00 and NAD 83(2011,MA11,PA11) epoch 2010.00. Although NGS relative calibrations can be and have been converted to absolute, it is considered best practice to independently measure phase center characteristics in an absolute sense. Consequently, NGS has developed and operates an absolute calibration system. These absolute antenna calibrations accommodate the demand for greater accuracy and for 2-dimensional (elevation and azimuth) parameterization. NGS will continue to provide calibration values via the NGS web site www.ngs.noaa.gov/ANTCAL, and will publish calibrations in the ANTEX format as well as the legacy ANTINFO

  4. Kids Count in Delaware, Families Count in Delaware: Fact Book, 2002.

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Kids Count in Delaware.

    This Kids Count Fact Book is combined with the Families Count Fact Book to provide information on statewide trends affecting children and families in Delaware. The Kids Count statistical profile is based on 11 main indicators of child well-being: (1) births to teens 15-17 years; (2) births to teens 10 to 14 years; (3) low birth weight babies; (3)…

  5. (18)F primary standard at ENEA-INMRI by three absolute techniques and calibration of a well-type IG11 ionization chamber.

    PubMed

    Capogni, Marco; Carconi, Pierluigi; De Felice, Pierino; Fazio, Aldo

    2016-03-01

    A new (18)F primary standardization carried out at ENEA-INMRI by three different absolute techniques, i.e. 4πγNaI(Tl)γ high-efficiency counting, TDCR and 4πβ(LS)-γ[NaI(Tl)] coincidence counting method, allowed the calibration of a fixed well-reentrant IG11 ionization chamber (IC), with an uncertainty lower than 1%, and to check the calibration factor of a portable well-type IC NPL-CRC model, previously calibrated. By the new standard the ENEA-INMRI was linked to the BIPM International Reference System (SIR) through the BIPM SIR Transfer Instrument (SIRTI).

  6. (18)F primary standard at ENEA-INMRI by three absolute techniques and calibration of a well-type IG11 ionization chamber.

    PubMed

    Capogni, Marco; Carconi, Pierluigi; De Felice, Pierino; Fazio, Aldo

    2016-03-01

    A new (18)F primary standardization carried out at ENEA-INMRI by three different absolute techniques, i.e. 4πγNaI(Tl)γ high-efficiency counting, TDCR and 4πβ(LS)-γ[NaI(Tl)] coincidence counting method, allowed the calibration of a fixed well-reentrant IG11 ionization chamber (IC), with an uncertainty lower than 1%, and to check the calibration factor of a portable well-type IC NPL-CRC model, previously calibrated. By the new standard the ENEA-INMRI was linked to the BIPM International Reference System (SIR) through the BIPM SIR Transfer Instrument (SIRTI). PMID:26774395

  7. Cosmology with velocity dispersion counts: an alternative to measuring cluster halo masses

    NASA Astrophysics Data System (ADS)

    Caldwell, C. E.; McCarthy, I. G.; Baldry, I. K.; Collins, C. A.; Schaye, J.; Bird, S.

    2016-11-01

    The evolution of galaxy cluster counts is a powerful probe of several fundamental cosmological parameters. A number of recent studies using this probe have claimed tension with the cosmology preferred by the analysis of the Planck primary cosmic microwave background (CMB) data, in the sense that there are fewer clusters observed than predicted based on the primary CMB cosmology. One possible resolution to this problem is systematic errors in the absolute halo mass calibration in cluster studies, which is required to convert the standard theoretical prediction (the halo mass function) into counts as a function of the observable (e.g. X-ray luminosity, Sunyaev-Zel'dovich flux, and optical richness). Here we propose an alternative strategy, which is to directly compare predicted and observed cluster counts as a function of the one-dimensional velocity dispersion of the cluster galaxies. We argue that the velocity dispersion of groups/clusters can be theoretically predicted as robustly as mass but, unlike mass, it can also be directly observed, thus circumventing the main systematic bias in traditional cluster counts studies. With the aid of the BAHAMAS suite of cosmological hydrodynamical simulations, we demonstrate the potential of the velocity dispersion counts for discriminating even similar Λ cold dark matter models. These predictions can be compared with the results from existing redshift surveys such as the highly complete Galaxy And Mass Assembly survey, and upcoming wide-field spectroscopic surveys such as the Wide Area Vista Extragalactic Survey and the Dark Energy Survey Instrument.

  8. Constitutive expression of genes encoding notch receptors and ligands in developing lymphocytes, nTreg cells and dendritic cells in the human thymus.

    PubMed

    Bento-de-Souza, Luciana; Victor, Jefferson R; Bento-de-Souza, Luiz C; Arrais-Santos, Magaly; Rangel-Santos, Andréia C; Pereira-Costa, Érica; Raniero-Fernandes, Elaine; Seixas-Duarte, Maria I; Oliveira-Filho, João B; Silva Duarte, Alberto J

    2016-01-01

    The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and ligands (DLL1-3 and Jagged1-2) constitute one of several pathways involved in this process. Our data revealed differential constitutive expression of Notch genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting their participation in human thymocyte maturation. nTreg analyses indicated that the Notch components function in parallel to promote maturation in the thymus. PMID:27504259

  9. B7-H4Ig inhibits mouse and human T-cell function and treats EAE via IL-10/Treg-dependent mechanisms☆

    PubMed Central

    Podojil, Joseph R.; Liu, Linda N.; Marshall, Shannon A.; Chiang, Ming-Yi; Goings, Gwen E.; Chen, Lieping; Langermann, Solomon; Miller, Stephen D.

    2014-01-01

    We evaluated the therapeutic efficacy and mechanisms of action of both mouse and human B7-H4 Immunoglobulin fusion proteins (mB7-H4Ig; hB7-H4Ig) in treating EAE. The present data show that mB7-H4Ig both directly and indirectly (via increasing Treg function) inhibited CD4+ T-cell proliferation and differentiation in both Th1- and Th17-cell promoting conditions while inducing production of IL-10. B7-H4Ig treatment effectively ameliorated progression of both relapsing (R-EAE) and chronic EAE correlating with decreased numbers of activated CD4+ T-cells within the CNS and spleen, and a concurrent increase in number and function of Tregs. The functional requirement for Treg activation in treating EAE was demonstrated by a loss of therapeutic efficacy of hB7-H4Ig in R-EAE following inactivation of Treg function either by anti-CD25 treatment or blockade of IL-10. Significant to the eventual translation of this treatment into clinical practice, hB7-H4Ig similarly inhibited the in vitro differentiation of naïve human CD4+ T-cells in both Th1- and Th17-promoting conditions, while promoting the production of IL-10. B7-H4Ig thus regulates pro-inflammatory T-cell responses by a unique dual mechanism of action and demonstrates significant promise as a therapeutic for autoimmune diseases, including MS. PMID:23683881

  10. Absolute pitch in infant auditory learning: evidence for developmental reorganization.

    PubMed

    Saffran, J R; Griepentrog, G J

    2001-01-01

    To what extent do infants represent the absolute pitches of complex auditory stimuli? Two experiments with 8-month-old infants examined the use of absolute and relative pitch cues in a tone-sequence statistical learning task. The results suggest that, given unsegmented stimuli that do not conform to the rules of musical composition, infants are more likely to track patterns of absolute pitches than of relative pitches. A 3rd experiment tested adults with or without musical training on the same statistical learning tasks used in the infant experiments. Unlike the infants, adult listeners relied primarily on relative pitch cues. These results suggest a shift from an initial focus on absolute pitch to the eventual dominance of relative pitch, which, it is argued, is more useful for both music and speech processing.

  11. Absolute calibration of sniffer probes on Wendelstein 7-X

    NASA Astrophysics Data System (ADS)

    Moseev, D.; Laqua, H. P.; Marsen, S.; Stange, T.; Braune, H.; Erckmann, V.; Gellert, F.; Oosterbeek, J. W.

    2016-08-01

    Here we report the first measurements of the power levels of stray radiation in the vacuum vessel of Wendelstein 7-X using absolutely calibrated sniffer probes. The absolute calibration is achieved by using calibrated sources of stray radiation and the implicit measurement of the quality factor of the Wendelstein 7-X empty vacuum vessel. Normalized absolute calibration coefficients agree with the cross-calibration coefficients that are obtained by the direct measurements, indicating that the measured absolute calibration coefficients and stray radiation levels in the vessel are valid. Close to the launcher, the stray radiation in the empty vessel reaches power levels up to 340 kW/m2 per MW injected beam power. Furthest away from the launcher, i.e., half a toroidal turn, still 90 kW/m2 per MW injected beam power is measured.

  12. Temporal Dynamics of Microbial Rhodopsin Fluorescence Reports Absolute Membrane Voltage

    PubMed Central

    Hou, Jennifer H.; Venkatachalam, Veena; Cohen, Adam E.

    2014-01-01

    Plasma membrane voltage is a fundamentally important property of a living cell; its value is tightly coupled to membrane transport, the dynamics of transmembrane proteins, and to intercellular communication. Accurate measurement of the membrane voltage could elucidate subtle changes in cellular physiology, but existing genetically encoded fluorescent voltage reporters are better at reporting relative changes than absolute numbers. We developed an Archaerhodopsin-based fluorescent voltage sensor whose time-domain response to a stepwise change in illumination encodes the absolute membrane voltage. We validated this sensor in human embryonic kidney cells. Measurements were robust to variation in imaging parameters and in gene expression levels, and reported voltage with an absolute accuracy of 10 mV. With further improvements in membrane trafficking and signal amplitude, time-domain encoding of absolute voltage could be applied to investigate many important and previously intractable bioelectric phenomena. PMID:24507604

  13. Absolute Value Boundedness, Operator Decomposition, and Stochastic Media and Equations

    NASA Technical Reports Server (NTRS)

    Adomian, G.; Miao, C. C.

    1973-01-01

    The research accomplished during this period is reported. Published abstracts and technical reports are listed. Articles presented include: boundedness of absolute values of generalized Fourier coefficients, propagation in stochastic media, and stationary conditions for stochastic differential equations.

  14. Absolute calibration of sniffer probes on Wendelstein 7-X.

    PubMed

    Moseev, D; Laqua, H P; Marsen, S; Stange, T; Braune, H; Erckmann, V; Gellert, F; Oosterbeek, J W

    2016-08-01

    Here we report the first measurements of the power levels of stray radiation in the vacuum vessel of Wendelstein 7-X using absolutely calibrated sniffer probes. The absolute calibration is achieved by using calibrated sources of stray radiation and the implicit measurement of the quality factor of the Wendelstein 7-X empty vacuum vessel. Normalized absolute calibration coefficients agree with the cross-calibration coefficients that are obtained by the direct measurements, indicating that the measured absolute calibration coefficients and stray radiation levels in the vessel are valid. Close to the launcher, the stray radiation in the empty vessel reaches power levels up to 340 kW/m(2) per MW injected beam power. Furthest away from the launcher, i.e., half a toroidal turn, still 90 kW/m(2) per MW injected beam power is measured. PMID:27587121

  15. Preparation of an oakmoss absolute with reduced allergenic potential.

    PubMed

    Ehret, C; Maupetit, P; Petrzilka, M; Klecak, G

    1992-06-01

    Synopsis Oakmoss absolute, an extract of the lichen Evernia prunastri, is known to cause allergenic skin reactions due to the presence of certain aromatic aldehydes such as atranorin, chloratranorin, ethyl hematommate and ethyl chlorohematommate. In this paper it is shown that treatment of Oakmoss absolute with amino acids such as lysine and/or leucine, lowers considerably the content of these allergenic constituents including atranol and chloratranol. The resulting Oakmoss absolute, which exhibits an excellent olfactive quality, was tested extensively in comparative studies on guinea pigs and on man. The results of the Guinea Pig Maximization Test (GPMT) and Human Repeated Insult Patch Test (HRIPT) indicate that, in comparison with the commercial test sample, the allergenicity of this new quality of Oakmoss absolute was considerably reduced, and consequently better skin tolerance of this fragrance for man was achieved. PMID:19272096

  16. Rapid, absolute calibration of x-ray filters employed by laser-produced plasma diagnostics.

    PubMed

    Brown, G V; Beiersdorfer, P; Emig, J; Frankel, M; Gu, M F; Heeter, R F; Magee, E; Thorn, D B; Widmann, K; Kelley, R L; Kilbourne, C A; Porter, F S

    2008-10-01

    The Electron Beam Ion Trap (EBIT) facility at the Lawrence Livermore National Laboratory is being used to absolutely calibrate the transmission efficiency of x-ray filters employed by diodes and spectrometers used to diagnose laser-produced plasmas. EBIT emits strong, discrete monoenergetic lines at appropriately chosen x-ray energies. X rays are detected using the high resolution EBIT Calorimeter Spectrometer (ECS), developed for LLNL at the NASA/Goddard Space Flight Center. X-ray filter transmission efficiency is determined by dividing the x-ray counts detected when the filter is in the line of sight by those detected when out of the line of sight. Verification of filter thickness can be completed in only a few hours, and absolute efficiencies can be calibrated in a single day over a broad range from about 0.1 to 15 keV. The EBIT calibration lab has been used to field diagnostics (e.g., the OZSPEC instrument) with fully calibrated x-ray filters at the OMEGA laser. Extensions to use the capability for calibrating filter transmission for the DANTE instrument on the National Ignition Facility are discussed. PMID:19044471

  17. Rapid, absolute calibration of x-ray filters employed by laser-produced plasma diagnostics

    SciTech Connect

    Brown, G. V.; Beiersdorfer, P.; Emig, J.; Frankel, M.; Gu, M. F.; Heeter, R. F.; Magee, E.; Thorn, D. B.; Widmann, K.; Kelley, R. L.; Kilbourne, C. A.; Porter, F. S.

    2008-10-15

    The Electron Beam Ion Trap (EBIT) facility at the Lawrence Livermore National Laboratory is being used to absolutely calibrate the transmission efficiency of x-ray filters employed by diodes and spectrometers used to diagnose laser-produced plasmas. EBIT emits strong, discrete monoenergetic lines at appropriately chosen x-ray energies. X rays are detected using the high resolution EBIT Calorimeter Spectrometer (ECS), developed for LLNL at the NASA/Goddard Space Flight Center. X-ray filter transmission efficiency is determined by dividing the x-ray counts detected when the filter is in the line of sight by those detected when out of the line of sight. Verification of filter thickness can be completed in only a few hours, and absolute efficiencies can be calibrated in a single day over a broad range from about 0.1 to 15 keV. The EBIT calibration lab has been used to field diagnostics (e.g., the OZSPEC instrument) with fully calibrated x-ray filters at the OMEGA laser. Extensions to use the capability for calibrating filter transmission for the DANTE instrument on the National Ignition Facility are discussed.

  18. Rapid, Absolute Calibration of X-ray Filters Employed By Laser-Produced Plasma Diagnostics

    SciTech Connect

    Brown, G V; Beiersdorfer, P; Emig, J; Frankel, M; Gu, M F; Heeter, R F; Magee, E; Thorn, D B; Widmann, K; . Kelley, R L; Kilbourne, C A; Porter, F S

    2008-05-11

    The electron beam ion trap (EBIT) facility at the Lawrence Livermore National Laboratory is being used to absolutely calibrate the transmission efficiency of X-ray filters employed by diodes and spectrometers used to diagnose laser-produced plasmas. EBIT emits strong, discrete monoenergetic lines at appropriately chosen X-ray energies. X-rays are detected using the high-resolution EBIT calorimeter spectrometer (ECS), developed for LLNL at the NASA/Goddard Space Flight Center. X-ray filter transmission efficiency is determined by dividing the X-ray counts detected when the filter is in the line of sight by those detected when out of the line of sight. Verification of filter thickness can be completed in only a few hours, and absolute efficiencies can be calibrated in a single day over a broad range from about 0.1 to 15 keV. The EBIT calibration lab has been used to field diagnostics (e.g., the OZSPEC instrument) with fully calibrated X-ray filters at the OMEGA laser. Extensions to use the capability for calibrating filter transmission for the DANTE instrument on the National Ignition Facility are discussed.

  19. Oxidized high-density lipoprotein accelerates atherosclerosis progression by inducing the imbalance between treg and teff in LDLR knockout mice.

    PubMed

    Ru, Ding; Zhiqing, He; Lin, Zhu; Feng, Wu; Feng, Zhang; Jiayou, Zhang; Yusheng, Ren; Min, Fan; Chun, Liang; Zonggui, Wu

    2015-05-01

    High density lipoprotein (HDL) dysfunction has been widely reported in clinic, and oxidation of HDL (ox-HDL) was shown to be one of the most common modifications in vivo and participate in the progression of atherosclerosis. But the behind mechanisms are still elusive. In this study, we firstly analyzed and found strong relationship between serum ox-HDL levels and risk factors of coronary artery diseases in clinic, then the effects of ox-HDL in initiation and progression of atherosclerosis in LDLR knockout mice were investigated by infusion of ox-HDL dissolved in chitosan hydrogel before the formation of lesions in vivo. Several new evidence were shown: (i) the serum levels of ox-HDL peaked early before the formation of lesions in LDLR mice fed with high fat diet similar to oxidative low density lipoprotein, (ii) the formation of atherosclerotic lesions could be accelerated by infusion of ox-HDL, (iii) the pro-atherosclerotic effects of ox-HDL were accompanied by imbalanced levels of effector and regulatory T cells and relative gene expressions, which implied that imbalance of teff and treg might contribute to the pro-atherosclerosis effects of ox-HDL.

  20. Oxidized high-density lipoprotein accelerates atherosclerosis progression by inducing the imbalance between treg and teff in LDLR knockout mice.

    PubMed

    Ru, Ding; Zhiqing, He; Lin, Zhu; Feng, Wu; Feng, Zhang; Jiayou, Zhang; Yusheng, Ren; Min, Fan; Chun, Liang; Zonggui, Wu

    2015-05-01

    High density lipoprotein (HDL) dysfunction has been widely reported in clinic, and oxidation of HDL (ox-HDL) was shown to be one of the most common modifications in vivo and participate in the progression of atherosclerosis. But the behind mechanisms are still elusive. In this study, we firstly analyzed and found strong relationship between serum ox-HDL levels and risk factors of coronary artery diseases in clinic, then the effects of ox-HDL in initiation and progression of atherosclerosis in LDLR knockout mice were investigated by infusion of ox-HDL dissolved in chitosan hydrogel before the formation of lesions in vivo. Several new evidence were shown: (i) the serum levels of ox-HDL peaked early before the formation of lesions in LDLR mice fed with high fat diet similar to oxidative low density lipoprotein, (ii) the formation of atherosclerotic lesions could be accelerated by infusion of ox-HDL, (iii) the pro-atherosclerotic effects of ox-HDL were accompanied by imbalanced levels of effector and regulatory T cells and relative gene expressions, which implied that imbalance of teff and treg might contribute to the pro-atherosclerosis effects of ox-HDL. PMID:25912129