Effects of symmetrical voltage sags on squirrel-cage induction motors

Energy Technology Data Exchange (ETDEWEB)

Pedra, Joaquin; Sainz, Luis; Corcoles, Felipe [Department of Electrical Engineering, ETSEIB-UPC, Av. Diagonal, 647, 08028 Barcelona (Spain)

2007-10-15

This paper analyzes the symmetrical voltage sag consequences on the induction motor behavior when single- and double-cage models are considered, namely current and torque peaks, and speed loss. These effects depend on several variables like sag type, duration and depth. Voltage sag effects are studied by using single- and double-cage models for three motors of different rated power. The double-cage model always predicts torque and current peaks higher than those of the single-cage model. The single-cage model predicts that voltage sags can produce motor instability, whereas the double-cage model is always stable. Therefore, the double-cage model must be used for the simulation of the squirrel-cage induction motor, because the single-cage model can give erroneous results in some situations. (author)

SnSAG5 is an alternative surface antigen of Sarcocystis neurona strains that is mutually exclusive to SnSAG1.

Science.gov (United States)

Crowdus, Carolyn A; Marsh, Antoinette E; Saville, Willliam J; Lindsay, David S; Dubey, J P; Granstrom, David E; Howe, Daniel K

2008-11-25

Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). Previous work has identified a gene family of paralogous surface antigens in S. neurona called SnSAGs. These surface proteins are immunogenic in their host animals, and are therefore candidate molecules for development of diagnostics and vaccines. However, SnSAG diversity exists in strains of S. neurona, including the absence of the major surface antigen gene SnSAG1. Instead, sequence for an alternative SnSAG has been revealed in two of the SnSAG1-deficient strains. Herein, we present data characterizing this new surface protein, which we have designated SnSAG5. The results indicated that the protein encoded by the SnSAG5 sequence is indeed a surface-associated molecule that has characteristics consistent with the other SAGs identified in S. neurona and related parasites. Importantly, Western blot analyses of a collection of S. neurona strains demonstrated that 6 of 13 parasite isolates express SnSAG5 as a dominant surface protein instead of SnSAG1. Conversely, SnSAG5 was not detected in SnSAG1-positive strains. One strain, which was isolated from the brain of a sea otter, did not express either SnSAG1 or SnSAG5. Genetic analysis with SnSAG5-specific primers confirmed the presence of the SnSAG5 gene in Western blot-positive strains, while also suggesting the presence of a novel SnSAG sequence in the SnSAG1-deficient, SnSAG5-deficient otter isolate. The findings provide further indication of S. neurona strain diversity, which has implications for diagnostic testing and development of vaccines against EPM as well as the population biology of Sarcocystis cycling in the opossum definitive host.

An Estimation Method of System Voltage Sag Profile using Recorded Sag Data

Science.gov (United States)

Tanaka, Kazuyuki; Sakashita, Tadashi

The influence of voltage sag to electric equipment has become big issues because of wider utilization of voltage sensitive devices. In order to reduce the influence of voltage sag appearing at each customer side, it is necessary to recognize the level of receiving voltage drop due to lightning faults for transmission line. However it is hard to measure directly those sag level at every load node. In this report, a new method of efficiently estimating system voltage sag profile is proposed based on symmetrical coordinate. In the proposed method, limited recorded sag data is used as the estimation condition which is recorded at each substation in power systems. From the point of view that the number of the recorded node is generally far less than those of the transmission route, a fast solution method is developed to calculate only recorder faulted voltage by applying reciprocity theorem for Y matrix. Furthermore, effective screening process is incorporated, in which the limited candidate of faulted transmission line can be chosen. Demonstrative results are presented using the IEEJ East10 standard system and actual 1700 bus system. The results show that estimation accuracy is sufficiently acceptable under less computation labor.

Anti-IL-2 treatment impairs the expansion of T(reg cell population during acute malaria and enhances the Th1 cell response at the chronic disease.

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Cláudia A Zago

Full Text Available Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+ T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory T (T(reg cells has been implicated in both development of clinical immunity and parasite persistence. To evaluate whether IL-2 is required to induce and to sustain the suppressive activity of T(reg cells in malaria, we examined in detail the effects of anti-IL-2 treatment with JES6-1 monoclonal antibody (mAb on the splenic CD4(+ T cell response during acute and chronic P. chabaudi AS infection in C57BL/6 mice. JES6-1 treatment on days 0, 2 and 4 of infection partially inhibits the expansion of the CD4(+CD25(+Foxp3(+ cell population during acute malaria. Despite the concomitant secretion of IL-2 and expression of high affinity IL-2 receptor by large CD4(+ T cells, JES6-1 treatment does not impair effector CD4(+ T cell activation and IFN-γ production. However, at the chronic phase of the disease, an enhancement of cellular and humoral responses occurs in JES6-1-treated mice, with increased production of TNF-α and parasite-specific IgG2a antibodies. Furthermore, JES6-1 mAb completely blocked the in vitro proliferation of CD4(+ T cells from non-treated chronic mice, while it further increased the response of CD4(+ T cells from JES6-1-treated chronic mice. We conclude that JES6-1 treatment impairs the expansion of T(reg cell population during early P. chabaudi malaria and enhances the Th1 cell response in the late phase of the disease.

Power conditioning using dynamic voltage restorers under different voltage sag types.

Science.gov (United States)

Saeed, Ahmed M; Abdel Aleem, Shady H E; Ibrahim, Ahmed M; Balci, Murat E; El-Zahab, Essam E A

2016-01-01

Voltage sags can be symmetrical or unsymmetrical depending on the causes of the sag. At the present time, one of the most common procedures for mitigating voltage sags is by the use of dynamic voltage restorers (DVRs). By definition, a DVR is a controlled voltage source inserted between the network and a sensitive load through a booster transformer injecting voltage into the network in order to correct any disturbance affecting a sensitive load voltage. In this paper, modelling of DVR for voltage correction using MatLab software is presented. The performance of the device under different voltage sag types is described, where the voltage sag types are introduced using the different types of short-circuit faults included in the environment of the MatLab/Simulink package. The robustness of the proposed device is evaluated using the common voltage sag indices, while taking into account voltage and current unbalance percentages, where maintaining the total harmonic distortion percentage of the load voltage within a specified range is desired. Finally, several simulation results are shown in order to highlight that the DVR is capable of effective correction of the voltage sag while minimizing the grid voltage unbalance and distortion, regardless of the fault type.

Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

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Han Seung

2010-06-01

Full Text Available Abstract Background Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. Results Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s. Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. Conclusion Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

The Treg/Th17 axis: A dynamic balance regulated by the gut microbiome

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Sara eOmenetti

2015-12-01

Full Text Available T-helper 17 (Th17 and T-regulatory (Treg cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 cells and Tregs share similar developmental requirements. In fact, the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6 and all-trans retinoic acid (RA. Importantly, the intestinal microbiome also provides immunostimulatory signals, which can activate innate, and downstream adaptive, immune responses. Specific components of the gut microbiome have been implicated in the production of proinflammatory cytokines by innate immune cells, such as IL-6, IL-23, IL-1β, and the subsequent generation and expansion of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of intestinal Tregs that can actively induce mucosal tolerance. As such, dysbiosis of the gut microbiome may not solely represent a consequence of gut inflammation, but rather shape the Treg/Th17 commitment and influence susceptibility to inflammatory bowel disease (IBD. In this review, we discuss Treg and Th17 cell plasticity, its dynamic regulation by the microbiome, and highlight its impact on intestinal homeostasis and disease.

Antimicrobial Tolerance of Pseudomonas aeruginosa Biofilms Is Activated during an Early Developmental Stage and Requires the Two-Component Hybrid SagS

Science.gov (United States)

Gupta, Kajal; Marques, Cláudia N. H.; Petrova, Olga E.

2013-01-01

A hallmark characteristic of biofilms is their extraordinary tolerance to antimicrobial agents. While multiple factors are thought to contribute to the high level of antimicrobial tolerance of biofilms, little is known about the timing of induction of biofilm tolerance. Here, we asked when over the course of their development do biofilms gain their tolerance to antimicrobial agents? We demonstrate that in Pseudomonas aeruginosa, biofilm tolerance is linked to biofilm development, with transition to the irreversible attachment stage regulated by the two-component hybrid SagS, marking the timing when biofilms switch to the high-level tolerance phenotype. Inactivation of sagS rendered biofilms but not planktonic cells more susceptible to tobramycin, norfloxacin, and hydrogen peroxide. Moreover, inactivation of sagS also eliminated the recalcitrance of biofilms to killing by bactericidal antimicrobial agents, a phenotype comparable to that observed upon inactivation of brlR, which encodes a MerR-like transcriptional regulator required for biofilm tolerance. Multicopy expression of brlR in a ΔsagS mutant restored biofilm resistance and recalcitrance to killing by bactericidal antibiotics to wild-type levels. In contrast, expression of sagS did not restore the susceptibility phenotype of ΔbrlR mutant biofilms to wild-type levels, indicating that BrlR functions downstream of SagS. Inactivation of sagS correlated with reduced BrlR levels in biofilms, with the produced BrlR being impaired in binding to the previously described BrlR-activated promoters of the two multidrug efflux pump operons mexAB-oprM and mexEF-oprN. Our findings demonstrate that biofilm tolerance is linked to early biofilm development and SagS, with SagS contributing indirectly to BrlR activation. PMID:23995639

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

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Ying Pan

Full Text Available 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.

The Four types of Tregs in malignant lymphomas

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Wang Jing

2011-12-01

Full Text Available Abstract Regulatory T cells (Tregs are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a suppressor Tregs; (b malignant Tregs; (c direct tumor-killing Tregs; and (d incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas.

Analysis of miR-146a and miR-142-3p as Potential Markers of Freshly Isolated or In Vitro-Expanded Human Treg cells

DEFF Research Database (Denmark)

Holmstrøm, K; Pedersen, A E; Gad, M

2017-01-01

Regulatory CD4(+) T cells (Tregs) are pivotal for prevention of autoimmunity. The use of Tregs is therefore of increasing interest in in vitro drug screening assays as well as for a cytotherapy per se against autoimmune disorders. For both purposes, in vitro expansion of peripheral blood Tregs...... in the same markers in activated tTregs as opposed to naïve tTregs. In vitro-expanded Tregs could be identified based on FOXP3 expression, but with loss of a discriminate profile for miRNA candidates and a decline in FOXP3 when activated tTregs were expanded. Our data demonstrate miR-146a and 142-3p...... and cytotherapy as FOXP3 is pivotal for suppressive function....

Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung infection.

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Li, Jing; Dong, Xiaojing; Zhao, Lei; Wang, Xiao; Wang, Yan; Yang, Xi; Wang, Hong; Zhao, Weiming

2016-07-01

Natural killer (NK) cell is an important component in innate immunity, playing a critical role in bridging innate and adaptive immunity by modulating the function of other immune cells including T cells. In this study, we focused on the role of NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung infection. We found that NK cell-depleted mice showed decreased Th1 and Th17 cells, which was correlated with reduced interferon-γ, interleukin (IL)-12, IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor gamma t expression compared with mice treated with the isotype control antibody. In contrast, NK cell depletion significantly increased Treg in cell number and related transcription factor (Foxp3) expression. The opposite trends of changes of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg ratios. The data implicate that NK cells play an important role in host defence against chlamydial lung infection, mainly through maintaining Th1/Treg and Th17/Treg balance. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Traffic Flow at Sags : Theory, Modeling and Control

NARCIS (Netherlands)

Goni-Ros, B.

2016-01-01

Sag vertical curves (sags) are roadway sections along which the gradient increases gradually in the direction of traffic. Empirical observations show that, on freeways, traffic congestion often occurs at sags; actually, in some countries (e.g., Japan), sags are one of the most common types of

An impact analysis of the fault impedance on voltage sags

Energy Technology Data Exchange (ETDEWEB)

Ramos, Alessandro Candido Lopes [CELG - Companhia Energetica de Goias, Goiania, GO (Brazil). Generation and Transmission. System' s Operation Center], E-mail: alessandro.clr@celg.com.br; Batista, Adalberto Jose [Federal University of Goias (UFG), Goiania, GO (Brazil)], E-mail: batista@eee.ufg.br; Leborgne, Roberto Chouhy [Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)], E-mail: rcl@ece.ufrgs.br; Emiliano, Pedro Henrique Mota, E-mail: ph@phph.com.br

2009-07-01

This paper presents an impact analysis of the fault impedance, in terms of its module and angle, on voltage sags caused by faults. Symmetrical and asymmetrical faults are simulated, at transmission and distribution lines, by using a frequency-domain fault simulation software called ANAFAS. Voltage sags are monitored at buses where sensitive end-users are connected. In order to overcome some intrinsic limitations of this software concerning its automatic execution for several cases, a computational tool was developed in Java programming language. This solution allows the automatic simulation of cases including the effect of the fault position, the fault type, and the proper fault impedance. The main conclusion is that the module and angle of the fault impedance can have a significant influence on voltage sag depending on the fault characteristics. (author)

Quantifying the gantry sag on linear accelerators and introducing an MLC-based compensation strategy

Energy Technology Data Exchange (ETDEWEB)

Du Weiliang; Gao Song; Wang Xiaochun; Kudchadker, Rajat J. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

2012-04-15

Purpose: Gantry sag is one of the well-known sources of mechanical imperfections that compromise the spatial accuracy of radiation dose delivery. The objectives of this study were to quantify the gantry sag on multiple linear accelerators (linacs), to investigate a multileaf collimator (MLC)-based strategy to compensate for gantry sag, and to verify the gantry sag and its compensation with film measurements. Methods: The authors used the Winston-Lutz method to measure gantry sag on three Varian linacs. A ball bearing phantom was imaged with megavolt radiation fields at 10 deg. gantry angle intervals. The images recorded with an electronic portal imaging device were analyzed to derive the radiation isocenter and the gantry sag, that is, the superior-inferior wobble of the radiation field center, as a function of the gantry angle. The authors then attempted to compensate for the gantry sag by applying a gantry angle-specific correction to the MLC leaf positions. The gantry sag and its compensation were independently verified using film measurements. Results: Gantry sag was reproducible over a six-month measurement period. The maximum gantry sag was found to vary from 0.7 to 1.0 mm, depending on the linac and the collimator angle. The radiation field center moved inferiorly (i.e., away from the gantry) when the gantry was rotated from 0 deg. to 180 deg. After the MLC leaf position compensation was applied at 90 deg. collimator angle, the maximum gantry sag was reduced to <0.2 mm. The film measurements at gantry angles of 0 deg. and 180 deg. verified the inferior shift of the radiation fields and the effectiveness of MLC compensation. Conclusions: The results indicate that gantry sag on a linac can be quantitatively measured using a simple phantom and an electronic portal imaging device. Reduction of gantry sag is feasible by applying a gantry angle-specific correction to MLC leaf positions at 90 deg. collimator angle.

The GARP/Latent TGF-β1 complex on Treg cells modulates the induction of peripherally derived Treg cells during oral tolerance.

Science.gov (United States)

Edwards, Justin P; Hand, Timothy W; Morais da Fonseca, Denise; Glass, Deborah D; Belkaid, Yasmine; Shevach, Ethan M

2016-06-01

Treg cells can secrete latent TGF-β1 (LTGF-β1), but can also utilize an alternative pathway for transport and expression of LTGF-β1 on the cell surface in which LTGF-β1 is coupled to a distinct LTGF-β binding protein termed glycoprotein A repetitions predominant (GARP)/LRRC32. The function of the GARP/LTGF-β1 complex has remained elusive. Here, we examine in vivo the roles of GARP and TGF-β1 in the induction of oral tolerance. When Foxp3(-) OT-II T cells were transferred to wild-type recipient mice followed by OVA feeding, the conversion of Foxp3(-) to Foxp3(+) OT-II cells was dependent on recipient Treg cells. Neutralization of IL-2 in the recipient mice also abrogated this conversion. The GARP/LTGF-β1 complex on recipient Treg cells, but not dendritic cell-derived TGF-β1, was required for efficient induction of Foxp3(+) T cells and for the suppression of delayed hypersensitivity. Expression of the integrin αvβ8 by Treg cells (or T cells) in the recipients was dispensable for induction of Foxp3 expression. Transient depletion of the bacterial flora enhanced the development of oral tolerance by expanding Treg cells with enhanced expression of the GARP/LTGF-β1 complex. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells

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Kayo Ikeda

2017-11-01

Full Text Available Summary: Foxp3+ regulatory T (Treg cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs, including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3+ Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3+ Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation. : Treg cells regulate excess immune responses and are highly proliferative in vivo. Ikeda et al. find that branched-chain amino acids (BCAAs are essentially required to maintain expansion and the suppressive capacity of Treg cells via Slc3a2 and mTORC1. Keywords: Treg cells, amino acids, immunometabolism, immune regulation, transporter

Sarcocystis neurona merozoites express a family of immunogenic surface antigens that are orthologues of the Toxoplasma gondii surface antigens (SAGs) and SAG-related sequences.

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Howe, Daniel K; Gaji, Rajshekhar Y; Mroz-Barrett, Meaghan; Gubbels, Marc-Jan; Striepen, Boris; Stamper, Shelby

2005-02-01

Sarcocystis neurona is a member of the Apicomplexa that causes myelitis and encephalitis in horses but normally cycles between the opossum and small mammals. Analysis of an S. neurona expressed sequence tag (EST) database revealed four paralogous proteins that exhibit clear homology to the family of surface antigens (SAGs) and SAG-related sequences of Toxoplasma gondii. The primary peptide sequences of the S. neurona proteins are consistent with the two-domain structure that has been described for the T. gondii SAGs, and each was predicted to have an amino-terminal signal peptide and a carboxyl-terminal glycolipid anchor addition site, suggesting surface localization. All four proteins were confirmed to be membrane associated and displayed on the surface of S. neurona merozoites. Due to their surface localization and homology to T. gondii surface antigens, these S. neurona proteins were designated SnSAG1, SnSAG2, SnSAG3, and SnSAG4. Consistent with their homology, the SnSAGs elicited a robust immune response in infected and immunized animals, and their conserved structure further suggests that the SnSAGs similarly serve as adhesins for attachment to host cells. Whether the S. neurona SAG family is as extensive as the T. gondii SAG family remains unresolved, but it is probable that additional SnSAGs will be revealed as more S. neurona ESTs are generated. The existence of an SnSAG family in S. neurona indicates that expression of multiple related surface antigens is not unique to the ubiquitous organism T. gondii. Instead, the SAG gene family is a common trait that presumably has an essential, conserved function(s).

Sarcocystis neurona Merozoites Express a Family of Immunogenic Surface Antigens That Are Orthologues of the Toxoplasma gondii Surface Antigens (SAGs) and SAG-Related Sequences†

Science.gov (United States)

Howe, Daniel K.; Gaji, Rajshekhar Y.; Mroz-Barrett, Meaghan; Gubbels, Marc-Jan; Striepen, Boris; Stamper, Shelby

2005-01-01

Sarcocystis neurona is a member of the Apicomplexa that causes myelitis and encephalitis in horses but normally cycles between the opossum and small mammals. Analysis of an S. neurona expressed sequence tag (EST) database revealed four paralogous proteins that exhibit clear homology to the family of surface antigens (SAGs) and SAG-related sequences of Toxoplasma gondii. The primary peptide sequences of the S. neurona proteins are consistent with the two-domain structure that has been described for the T. gondii SAGs, and each was predicted to have an amino-terminal signal peptide and a carboxyl-terminal glycolipid anchor addition site, suggesting surface localization. All four proteins were confirmed to be membrane associated and displayed on the surface of S. neurona merozoites. Due to their surface localization and homology to T. gondii surface antigens, these S. neurona proteins were designated SnSAG1, SnSAG2, SnSAG3, and SnSAG4. Consistent with their homology, the SnSAGs elicited a robust immune response in infected and immunized animals, and their conserved structure further suggests that the SnSAGs similarly serve as adhesins for attachment to host cells. Whether the S. neurona SAG family is as extensive as the T. gondii SAG family remains unresolved, but it is probable that additional SnSAGs will be revealed as more S. neurona ESTs are generated. The existence of an SnSAG family in S. neurona indicates that expression of multiple related surface antigens is not unique to the ubiquitous organism T. gondii. Instead, the SAG gene family is a common trait that presumably has an essential, conserved function(s). PMID:15664946

Installation of the sag compensator for HANARO

International Nuclear Information System (INIS)

Kim, Hyung Kyoo; Jung, Hoan Sung; Lim, In Cheol; Ahn, Guk Hoon

2008-01-01

Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extent of sags occur. HANARO has the reactor regulation system(RRs) and reactor protection system(RPS). HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut off rods(SOR). When voltage sag or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells

Science.gov (United States)

Harker-Murray, Paul; Porter, Stephen B.; Merkel, Sarah C.; Londer, Aryel; Taylor, Dawn K.; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N.; Suhoski, Megan M.; Miller, Jeffrey S.; Wagner, John E.; June, Carl H.; Riley, James L.

2008-01-01

Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)–coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor β (TGF-β) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL. PMID:18645038

Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.

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Weiting Du

Full Text Available Foxp3(+ regulatory T cells (Treg play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D, and to prevent rejection of organ transplants. In view of the goal of developing autologous Treg-based cell therapy for patients with long-term (>15 years T1D, it will be necessary to expand a sufficient amount of functional Treg in vitro in order to study and compare Treg from T1D patients and healthy subjects. Our results have demonstrated that there is a comparable frequency of Treg in the peripheral blood lymphocytes (PBLs of patients with long-term T1D relative to those in healthy subjects; however, Th1 cells, but not Th17 cells, were increased in the T1D patients. Further, more Treg in PBLs from T1D patients than from healthy subjects expressed the CD45RO(+ memory cell phenotype, suggesting they were antigen-experienced cells. After isolation, Treg from both T1D patients and healthy subjects were successfully expanded with high purity. Although there was no difference in Helios expression on Treg in PBLs, in vitro expansion led to fewer Helios-expressing Treg from T1D patients than healthy subjects. While more Th1-like Treg expressing IFN-γ or TNF-α were found in the PBLs of T1D patients than healthy controls, there was no such difference in the expanded Treg. Importantly, expanded Treg from both subject groups were able to suppress autologous or allogeneic CD8(+ effector T cells equally well. Our findings demonstrate that a large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios. Thus, based on the positive outcomes, these potent expanded Treg from diabetic human patients may be useful in treating T1D or preventing islet graft rejection.

The success of assisted reproduction technologies in relation to composition of the total regulatory T cell (Treg) pool and different Treg subsets.

Science.gov (United States)

Schlossberger, V; Schober, L; Rehnitz, J; Schaier, M; Zeier, M; Meuer, S; Schmitt, E; Toth, B; Strowitzki, T; Steinborn, A

2013-11-01

Are there differences in composition of the total regulatory T cell (Treg) pool and distinct Treg subsets (naïve CD45RA(+)-Tregs, HLA-DR(-)- and HLA-DR(+)-memory Tregs) between successfully and non-successfully IVF/ICSI-treated women? Non-successfully IVF/ICSI-treated women have a decreased percentage of naïve CD45RA(+)-Tregs and an increased percentage of HLA-DR(-)-memory Tregs within the total Treg pool. Immunosuppressive Tregs play a significant role in human reproduction and studies have shown that their number and function are reduced in reproductive failure and complications of pregnancy such as pre-eclampsia and preterm labor. However, no data exist concerning the importance of Tregs for a successful outcome following assisted reproduction technologies. Blood samples were obtained from 210 women undergoing IVF/ICSI treatment, where 14 patients were excluded due to biochemical pregnancy or missed abortion. Age control blood samples were collected from 20 neonates and 176 healthy female volunteers. The study was performed between October 2010 and March 2012. In this study, we determined prospectively the quantity and composition of the total CD4(+)CD127(low+/-)CD25(+)FoxP3(+)-Treg pool and three different Treg subsets (naïve CD45RA(+)-Tregs, HLA-DR(-)- and HLA-DR(+)-memory Tregs) in all women undergoing IVF/ICSI treatment. We examined whether there were differences between those who became pregnant (n = 36) and those who did not (n = 160). The blood samples were collected within 1 h before the embryo transfer and analyzed by six-color flow cytometry. In order to evaluate these results with regard to the normal age-related changes in composition of the total Treg pool, the same analysis was performed using samples of umbilical cord blood and from healthy female volunteers aged between 17 and 76 years. The composition of the total Treg pool was documented for successfully IVF/ICSI-treated women (n = 5) throughout their pregnancy and we assessed the

Peritransplant Treg-Based Immunomodulation to Improve VCA Outcomes

Science.gov (United States)

2017-10-01

orthotopic limb allografts in conjunction with TCR mAb and/or WT or HDAC-/- Treg cell administration 6-12 Milestone(s) Achieved: Efficacy of polyclonal WT...demethylation for each population (WT Tregs, HDAC6-/- Tregs, HDAC11-/- Tregs). 10-12 Subtask 2: Perform orthotopic limb allografts in conjunction ...function, and assessment of TSDR demethylation. • Subtask 3: Perform orthotopic limb allografts in conjunction with TCR mAb and/or WT or HDAC-/- Treg cell

Suppressive and immunoprotective functions of Tregs

Directory of Open Access Journals (Sweden)

Pushpa ePandiyan

2011-11-01

Full Text Available CD4+CD25+Foxp3+ T lymphocytes, known as regulatory T cells or Tregs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of Tregs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells (APCs; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4+ effector T cells are directly inhibited by Tregs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion (PCD; and 4. Contrary to the current view, we discuss new evidence that Tregs, similar to other T cells lineages, can promote protective immune responses in certain infectious contexts (Pandiyan et al. 2011; Chen et al 2011. Although these points are at variance to varying degrees with the standard model of Treg behavior, we will recount developing findings that support these new concepts.

Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/− Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice

Directory of Open Access Journals (Sweden)

Séverine Bézie

2018-01-01

Full Text Available Both CD4+ and CD8+ Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8+ Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8+CD45RClow/− Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8+CD45RClow/− Tregs can be efficiently expanded in the presence of anti-CD3/28 mAbs, high-dose IL-2 and IL-15 and that such expanded Tregs efficiently delay GVHD and human skin transplantation rejection in immune humanized mice. Robustly expanded CD8+ Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. We show that CD8+CD45RClow/− Tregs are equivalent to canonical CD4+CD25highCD127low/− Tregs for suppression of allogeneic immune responses in vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD.

Installation of the sag compensator for HANARO

International Nuclear Information System (INIS)

Kim, Hyungkyoo; Jung, Hoansung; Lim, Incheol; Ahn, Gukhoon

2008-01-01

Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30 MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extent of sags occur. HANARO has the reactor regulation system(RRS) and reactor protection system(RPS). HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut-off rods(SOR). When voltage sag or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent an unwanted trip. We undertook voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator. (author)

A Simple Sag Generator Using SSRs

DEFF Research Database (Denmark)

Senturk, Osman Selcuk; Hava, Ahmet M.

2012-01-01

SSR (solid state relay, a semiconductor power module of triac characteristics) and variable transformer (variac) based sag generator is built for three-phase 10kVA ratings and balanced/imbalanced voltage sags are demonstrated in the laboratory. The performance under resistive and inductive loads...

Model Predictive Control for an Industrial SAG Mill

DEFF Research Database (Denmark)

Ohan, Valeriu; Steinke, Florian; Metzger, Michael

2012-01-01

identication. When applied to MIMO systems we call this controller a MIMO-ARX based MPC. We use an industrial Semi-Autogenous Grinding (SAG) mill to illustrate the performance of this controller. SAG mills are the primary units in a grinding chain and also the most power consuming units. Therefore, improved...... control of SAG mills has the potential to signicantly improve eciency and reduce the specic energy consumption for mineral processes. Grinding circuits involving SAG mills are multivariate processes. Commissioning of a control system based on a classical single-loop controllers with logic is time...

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Chao Yan

Full Text Available 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.

GILZ Promotes Production of Peripherally Induced Treg Cells and Mediates the Crosstalk between Glucocorticoids and TGF-β Signaling

Directory of Open Access Journals (Sweden)

Oxana Bereshchenko

2014-04-01

Full Text Available Regulatory T (Treg cells expressing the transcription factor forkhead box P3 (FoxP3 control immune responses and prevent autoimmunity. Treatment with glucocorticoids (GCs has been shown to increase Treg cell frequency, but the mechanisms of their action on Treg cell induction are largely unknown. Here, we report that glucocorticoid-induced leucine zipper (GILZ, a protein induced by GCs, promotes Treg cell production. In mice, GILZ overexpression causes an increase in Treg cell number, whereas GILZ deficiency results in impaired generation of peripheral Treg cells (pTreg, associated with increased spontaneous and experimental intestinal inflammation. Mechanistically, we found that GILZ is required for GCs to cooperate with TGF-β in FoxP3 induction, while it enhances TGF-β signaling by binding to and promoting Smad2 phosphorylation and activation of FoxP3 expression. Thus, our results establish an essential GILZ-mediated link between the anti-inflammatory action of GCs and the regulation of TGF-β-dependent pTreg production.

Installation of the sag compensator for HANARO

International Nuclear Information System (INIS)

Kim, H. K.; Jung, H. S.; Ahn, G. H.; Lim, I. C.

2008-01-01

Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extents of sags occur. HANARO has the reactor regulation system (RRS) and reactor protection system (RPS). HANARO is designed so as to tripped automatically by insertion of control absorber rods (CAR) and shut-off rods (SOR). When voltage or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent an unwanted trip. We undertook voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

Survey of the rubber tree genome reveals a high number of cysteine protease-encoding genes homologous to Arabidopsis SAG12.

Science.gov (United States)

Zou, Zhi; Liu, Jianting; Yang, Lifu; Xie, Guishui

2017-01-01

Arabidopsis thaliana SAG12, a senescence-specific gene encoding a cysteine protease, is widely used as a molecular marker for the study of leaf senescence. To date, its potential orthologues have been isolated from several plant species such as Brassica napus and Nicotiana tabacum. However, little information is available in rubber tree (Hevea brasiliensis), a rubber-producing plant of the Euphorbiaceae family. This study presents the identification of SAG12-like genes from the rubber tree genome. Results showed that an unexpected high number of 17 rubber orthologues with a single intron were found, contrasting the single copy with two introns in Arabidopsis. The gene expansion was also observed in another two Euphorbiaceae plants, castor bean (Ricinus communis) and physic nut (Jatropha curcas), both of which contain 8 orthologues. In accordance with no occurrence of recent whole-genome duplication (WGD) events, most duplicates in castor and physic nut were resulted from tandem duplications. In contrast, the duplicated HbSAG12H genes were derived from tandem duplications as well as the recent WGD. Expression analysis showed that most HbSAG12H genes were lowly expressed in examined tissues except for root and male flower. Furthermore, HbSAG12H1 exhibits a strictly senescence-associated expression pattern in rubber tree leaves, and thus can be used as a marker gene for the study of senescence mechanism in Hevea.

A new approach to voltage sag detection based on wavelet transform

Energy Technology Data Exchange (ETDEWEB)

Gencer, Oezguer; Oeztuerk, Semra; Erfidan, Tarik [Kocaeli University, Faculty of Engineering, Department of Electrical Engineering, Veziroglu Kampuesue, Eski Goelcuek Yolu, Kocaeli (Turkey)

2010-02-15

In this work, a new voltage sag detection method based on wavelet transform is developed. Voltage sag detection algorithms, so far have proved their efficiency and computational ability. Using several windowing techniques take long computational times for disturbance detection. Also researchers have been working on separating voltage sags from other voltage disturbances for the last decade. Due to increasing power quality standards new high performance disturbance detection algorithms are necessary to obtain high power quality standards. For this purpose, the wavelet technique is used for detecting voltage sag duration and magnitude. The developed voltage sag detection algorithm is implemented with high speed microcontroller. Test results show that, the new approach provides very accurate and satisfactory voltage sag detection. (author)

Voltage sags impact on CAR and SOR of HANARO

International Nuclear Information System (INIS)

Kim, Hyung Kyoo; Jung, Hoan Sung; Wu, Jong Sup

2004-01-01

The combination of the unstable electric power and sensitive equipment may cause the nuisance of reactor trip. The reactor is tripped by the RRS and RPS during the occurrence of the voltage sags or momentary interruptions. We tested the components of RRS and RPS for the immunity from voltage sags and momentary interruptions. The tested components are DC power supply for CAR (control absorbed rod) of RRS and AC coil contactor for SOR (shut off rod) of RPS. We briefly describe the power quality standard for the voltage sags. This paper summarizes the magnitudes and durations of the voltage sags which impact on the CAR and SOR system

Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion.

Science.gov (United States)

Kadle, Rohini L; Abdou, Salma A; Villarreal-Ponce, Alvaro P; Soares, Marc A; Sultan, Darren L; David, Joshua A; Massie, Jonathan; Rifkin, William J; Rabbani, Piul; Ceradini, Daniel J

2018-01-01

Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs. We observed that priming MSCs in hypoxia promotes maintenance of stem-like characteristics, with greater expression of typical MSC cell-surface markers, increased proliferation, and maintenance of differentiation potential. Addition of autologous MSCs to CD4+/allogeneic endothelial cell (EC) co-culture increases regulatory T cell (Treg) proliferation, which is further enhanced when MSCs are primed in hypoxia. Furthermore, MSC-mediated Treg expansion does not require direct cell-cell contact. The expression of indolamine 2,3-dioxygenase, a mediator of MSC immunomodulation, increases when MSCs are primed in hypoxia, and inhibition of IDO significantly decreases the expansion of Tregs. Priming with inflammatory cytokines IFNγ and TNFα increases also expression of markers associated with MSC immunomodulatory function, but decreases MSC proliferation. The expression of IDO also increases when MSCs are primed with inflammatory cytokines. However, there is no increase in Treg expansion when MSCs are primed with IFNγ, suggesting an alternate mechanism for inflammatory-stimulated MSC immunomodulation. Overall, these results suggest that MSCs primed in hypoxia or inflammatory conditions are optimally primed for immunosuppressive function. These results provide a clearer picture of how to enhance MSC immunomodulation for clinical use.

Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

Science.gov (United States)

Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

2018-01-01

To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

Research on uncertainty evaluation measure and method of voltage sag severity

Science.gov (United States)

Liu, X. N.; Wei, J.; Ye, S. Y.; Chen, B.; Long, C.

2018-01-01

Voltage sag is an inevitable serious problem of power quality in power system. This paper focuses on a general summarization and reviews on the concepts, indices and evaluation methods about voltage sag severity. Considering the complexity and uncertainty of influencing factors, damage degree, the characteristics and requirements of voltage sag severity in the power source-network-load sides, the measure concepts and their existing conditions, evaluation indices and methods of voltage sag severity have been analyzed. Current evaluation techniques, such as stochastic theory, fuzzy logic, as well as their fusion, are reviewed in detail. An index system about voltage sag severity is provided for comprehensive study. The main aim of this paper is to propose thought and method of severity research based on advanced uncertainty theory and uncertainty measure. This study may be considered as a valuable guide for researchers who are interested in the domain of voltage sag severity.

Evolution of density-dependent movement during experimental range expansions.

Science.gov (United States)

Fronhofer, E A; Gut, S; Altermatt, F

2017-12-01

Range expansions and biological invasions are prime examples of transient processes that are likely impacted by rapid evolutionary changes. As a spatial process, range expansions are driven by dispersal and movement behaviour. Although it is widely accepted that dispersal and movement may be context-dependent, for instance density-dependent, and best represented by reaction norms, the evolution of density-dependent movement during range expansions has received little experimental attention. We therefore tested current theory predicting the evolution of increased movement at low densities at range margins using highly replicated and controlled range expansion experiments across multiple genotypes of the protist model system Tetrahymena thermophila. Although rare, we found evolutionary changes during range expansions even in the absence of initial standing genetic variation. Range expansions led to the evolution of negatively density-dependent movement at range margins. In addition, we report the evolution of increased intrastrain competitive ability and concurrently decreased population growth rates in range cores. Our findings highlight the importance of understanding movement and dispersal as evolving reaction norms and plastic life-history traits of central relevance for range expansions, biological invasions and the dynamics of spatially structured systems in general. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Voltage sags: Their impact on the utility and industrial customers

International Nuclear Information System (INIS)

Davis, T.; Beam, G.E.; Melhorn, C.J.

1995-01-01

This paper describes the impact of voltage sags on the utility and industrial customers. Several utility measures are presented to minimize the customer's exposure to voltage sags. However, these measures cannot completely eliminate the impact of voltage sags on sensitive equipment. A case study is presented in this paper that includes measurement results that were used to characterize the voltage sags experienced on the utility system and in the industrial facility, simulation results that were used to develop area of vulnerability curves for the industrial facility, mitigation equipment that was employed to improve the sensitive equipment's ride through capability, and the lessons learned from the systems approach analysis

Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion1

Science.gov (United States)

Turner, Michael S.; Kane, Lawrence P.; Morel, Penelope A.

2009-01-01

The definitions of tolerogenic vs. immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allo-antigens. However, we have previously reported that mature DC (G4DC) prevented the onset of autoimmune diabetes whereas immature DC (GMDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR Tg mice were stimulated, in the absence of exogenous cytokine, with GMDC or G4DC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both GMDC and G4DC presenting low peptide doses induced weak TCR signaling via the Akt/mTOR pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed G4DC, but not GMDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-Tg T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with antigen dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low antigen doses. These studies indicate that strength of Akt/mTOR signaling, a critical T cell intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production. PMID:19801514

Transmission line sag calculations using interval mathematics

Energy Technology Data Exchange (ETDEWEB)

Shaalan, H. [Institute of Electrical and Electronics Engineers, Washington, DC (United States)]|[US Merchant Marine Academy, Kings Point, NY (United States)

2007-07-01

Electric utilities are facing the need for additional generating capacity, new transmission systems and more efficient use of existing resources. As such, there are several uncertainties associated with utility decisions. These uncertainties include future load growth, construction times and costs, and performance of new resources. Regulatory and economic environments also present uncertainties. Uncertainty can be modeled based on a probabilistic approach where probability distributions for all of the uncertainties are assumed. Another approach to modeling uncertainty is referred to as unknown but bounded. In this approach, the upper and lower bounds on the uncertainties are assumed without probability distributions. Interval mathematics is a tool for the practical use and extension of the unknown but bounded concept. In this study, the calculation of transmission line sag was used as an example to demonstrate the use of interval mathematics. The objective was to determine the change in cable length, based on a fixed span and an interval of cable sag values for a range of temperatures. The resulting change in cable length was an interval corresponding to the interval of cable sag values. It was shown that there is a small change in conductor length due to variation in sag based on the temperature ranges used in this study. 8 refs.

Responsive demand to mitigate slow recovery voltage sags

DEFF Research Database (Denmark)

Garcia-Valle, Rodrigo; da Silva, Luiz Carlos Pereira; Xu, Zhao

2012-01-01

, and reactive power reserve for peak load management through price responsive methods and also as energy providers through embedded generation technologies. This article introduces a new technology, called demand as voltagecontrolled reserve, which can help mitigation of momentary voltage sags. The technology...... faults. This article presents detailed models, discussion, and simulation tests to demonstrate the technical viability and effectiveness of the demand as voltage-controlled reserve technology for mitigating voltage sags....... can be provided by thermostatically controlled loads as well as other types of load. This technology has proven to be effective in distribution systems with a large composition of induction motors, when voltage sags present slow recovery characteristics because of the deceleration of the motors during...

Treg/IL-17 ratio and Treg differentiation in patients with COPD.

Directory of Open Access Journals (Sweden)

Yang Jin

Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic pulmonary and systematic inflammation. An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes. T-helper (Th, T-cytotoxic (Tc and T-regulatory (Treg cells may play important roles in immune and inflammatory responses. This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD.Twenty-three patients with stable COPD (SCOPD and 21 patients with AECOPD were enrolled in the present study. In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls. The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9 were measured by enzyme-linked immunosorbent assay (ELISA kits. Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies. Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment. There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups. Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient. Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions

Voltage Sag due to Pollution Induced Flashover Across Ceramic Insulator Strings

Science.gov (United States)

Reddy B, Subba; Goswami, Arup Kumar

2017-11-01

Voltage sag or voltage dips are significant to industrial reliability. There is a necessity to characterize the feeder level power quality (PQ) and the PQ performance among various utility companies. Contamination/pollution induced flashover is the ultimate consequence of the creeping discharges across the insulator strings which induce voltage sag. These have a severe threat on the safe and reliable operation of power systems. In the present work an attempt has been made to experimentally investigate the occurrence of voltage sag/dips during pollution induced flashovers. Results show significant dip/sag in the voltage magnitude during the flashover process.

Effects of balanced and unbalanced voltage sags on DC adjustable-speed drives

Energy Technology Data Exchange (ETDEWEB)

Pedra, Joaquin; Sainz, Luis; Corcoles, Felipe; Bergas, Joan [Department of Electrical Engineering, ETSEIB-UPC, Av. Diagonal, 647, 08028 Barcelona (Spain); de Blas, Alfredo [Department of Electrical Engineering, EUETIB-UPC, C. d' Urgell, 187, 08036 Barcelona (Spain)

2008-06-15

This paper analyzes the sensitivity of DC adjustable-speed drives to balanced and unbalanced voltage sags. The influence of sag type, depth, duration and phase-angle jump on DC drives is studied. The control of the DC drive has been taken into account to understand drive behavior in the presence of voltage sags. Two working modes of the DC motor are considered in the study: as a consumer load and as a regenerative load. When the DC motor works as a consumer load, the study shows that sag type and depth have a significant influence on drive behavior. However, the voltage sag can be ridden through if the rectifier firing angle is set correctly by the control. When the DC motor works as a regenerative load, the study shows the consequences of the three-phase rectifier commutation failure due to the voltage sag. (author)

Compensation for gravitational sag of bent mirror

Energy Technology Data Exchange (ETDEWEB)

Mao, Chengwen; Jiang, Hui; He, Yan; Liang, Dongxu; Lan, Xuying; Yan, Shuai [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, CAS, Shanghai 201800 (China); Shu, De-ming [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); Li, Aiguo, E-mail: aiguo.li@sinap.ac.cn [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, CAS, Shanghai 201800 (China)

2017-05-01

The gravitational sag of aspheric bent mirrors with face-up or face-down geometry produces a nonnegligible optical error. As an effective compensation, width optimization is used to match the combined effects of the gravitational and bending moments. This method is described by analytical expressions and two calculation algorithms. The results of theoretical simulations and finite element analysis have proved that this method can reduce the slope error resulting from gravitational sag to the level of nano radians.

Compensation for gravitational sag of bent mirror

International Nuclear Information System (INIS)

Mao, Chengwen; Jiang, Hui; He, Yan; Liang, Dongxu; Lan, Xuying; Yan, Shuai; Shu, De-ming; Li, Aiguo

2017-01-01

The gravitational sag of aspheric bent mirrors with face-up or face-down geometry produces a nonnegligible optical error. As an effective compensation, width optimization is used to match the combined effects of the gravitational and bending moments. This method is described by analytical expressions and two calculation algorithms. The results of theoretical simulations and finite element analysis have proved that this method can reduce the slope error resulting from gravitational sag to the level of nano radians.

Computation and measurement of calandria tube sag in PHWR

International Nuclear Information System (INIS)

Kim, Tae Ryong; Sohn, Seok Man

2003-01-01

Calandria tubes and liquid injection shutdown system (LISS) tubes in a pressurized heavy water reactor (PHWR) is known to sag due to irradiation creep and growth during plant operation. When the sag of calandria tube becomes bigger, the calandria tube possibly comes in contact with LISS tube crossing beneath and calandria tube. The contact subsequently may cause the damage on the calandria tube resulting in unpredicted outage of the plant. It is therefore necessary to check the gap between the two tubes in order to periodically confirm no contact by using a proper measure during the plant life. An ultrasonic gap measuring probe assembly which can be inserted into two viewing ports of the calandria was developed in Korea and utilized to measure the sags of both tubes in the PHWR. It was found that the centerlines of calandria tubes and liquid injection shutdown system tubes can be precisely detected by ultrasonic wave. The gaps between two tubes were easily obtained from the relative distance of the measured centerline elevations of the tubes. Based on the irradiation creep equation and the measurement data, a computer program to calculate the sags was also developed. With the computer program, the sag at the end of plant life was predicted. (author)

3, 3'-Diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance.

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Liu, Yun; She, Weimin; Wang, Fuping; Li, Jing; Wang, Jiyao; Jiang, Wei

2014-12-01

This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset. Besides, with the assistance of AhR antagonist CH223191 and anti-TLR4 neutralizing antibody, we designed the in-vitro DIM-incubation experiments to discuss the roles of aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1B1) and toll-like receptor 4 (TLR4) on DIM's effects when shifting Treg/Th17 imbalance. Notably, in NASH mouse models, DIM alleviated hepatic steatosis and inflammation, and shifted the Treg/Th17 imbalance from MCD diet-induced Th17 dominance to Treg dominance. In-vitro, DIM not only significantly up-regulated the mRNAs of Foxp3 (Treg-specific) in purified spleen CD4(+) T cells, but also enhanced the immunosuppressive function of these Treg cells. Besides, DIM significantly up-regulated the proteins of CYP1A1 and CYP1B1 whereas down-regulated those of TLR4 on CD4(+) T cells from MCD-diet mice. Moreover, blocking AhR attenuated while blocking TLR4 enhanced the effects of DIM when regulating Treg/Th17 imbalance. Conclusively, DIM could be used as a potential therapeutic candidate to treat NASH based on its dramatic induction of Treg dominance to alleviate intra-hepatic inflammation, suggesting us a clue that the dietary cruciferous vegetables (containing abundant DIM) might exist as a protective factor for patients with NASH-related liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential effects of IL-2 and IL-21 on expansion of the CD4+ CD25+ Foxp3+ T regulatory cells with redundant roles in natural killer cell mediated antibody dependent cellular cytotoxicity in chronic lymphocytic leukemia.

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Gowda, Aruna; Ramanunni, Asha; Cheney, Carolyn; Rozewski, Darlene; Kindsvogel, Wayne; Lehman, Amy; Jarjoura, David; Caligiuri, Michael; Byrd, John C; Muthusamy, Natarajan

2010-01-01

CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4(+)CD25(Intermediate) or CD4(+)CD25(Dim/-) T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25(+)Foxp3(+)T cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.

Changes in natural Foxp3(+Treg but not mucosally-imprinted CD62L(negCD38(+Foxp3(+Treg in the circulation of celiac disease patients.

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Marieke A van Leeuwen

Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammation driven by gluten-reactive CD4(+ T cells. Due to lack of selective markers it has not been determined whether defects in inducible regulatory T cell (Treg differentiation are associated with CD. This is of importance as changes in numbers of induced Treg could be indicative of defects in mucosal tolerance development in CD. Recently, we have shown that, after encounter of retinoic acid during differentiation, circulating gut-imprinted T cells express CD62L(negCD38(+. Using this new phenotype, we now determined whether alterations occur in the frequency of natural CD62L(+Foxp3(+ Treg or mucosally-imprinted CD62L(negCD38(+Foxp3(+ Treg in peripheral blood of CD patients. In particular, we compared pediatric CD, aiming to select for disease at onset, with adult CD. METHODS: Cell surface markers, intracellular Foxp3 and Helios were determined by flow cytometry. Foxp3 expression was also detected by immunohistochemistry in duodenal tissue of CD patients. RESULTS: In children, the percentages of peripheral blood CD4(+Foxp3(+ Treg were comparable between CD patients and healthy age-matched controls. Differentiation between natural and mucosally-imprinted Treg on the basis of CD62L and CD38 did not uncover differences in Foxp3. In adult patients on gluten-free diet and in refractory CD increased percentages of circulating natural CD62L(+Foxp3(+ Treg, but normal mucosally-imprinted CD62L(negCD38(+Foxp3(+ Treg frequencies were observed. CONCLUSIONS: Our data exclude that significant numeric deficiency of mucosally-imprinted or natural Foxp3(+ Treg explains exuberant effector responses in CD. Changes in natural Foxp3(+ Treg occur in a subset of adult patients on a gluten-free diet and in refractory CD patients.

The Treg/Th17 Paradigm in Lung Cancer

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Min-Chao Duan

2014-01-01

Full Text Available Pathogenic mechanisms underlying the development of lung cancer are very complex and not yet entirely clarified. T lymphocytes and their immune-regulatory cytokines play a pivotal role in controlling tumor growth and metastasis. Following activation by unique cytokines, CD4+ T helper cells differentiate into Th1, Th2, Th17, and regulatory T cells (Tregs. Traditionally, research in lung cancer immunity has focused almost exclusively on Th1/Th2 cell balance. Recently, Th17 cells and Tregs represent an intriguing issue to be addressed in lung cancer pathogenesis. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against tumor cells. Th17 cells directly or via other proinflammatory cytokines modulate antitumor immune responses. Notably, there is a close relation between Tregs and Th17 cells. However, the possible interaction between these subsets in lung cancer remains to be elucidated. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent a useful tool for lung cancer treatment in the future. The purpose of this review is to discuss recent findings of the role of these novel populations in lung cancer immunity and to highlight the pleiotropic effects of these subsets on the development and regulation of lung cancer.

Increased Th17/Treg Ratio in Poststroke Fatigue

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Xinjing Liu

2015-01-01

Full Text Available Fatigue is a major debilitating symptom after stroke. The biological mechanisms underlying poststroke fatigue (PFS are unknown. We hypothesized that PSF is associated with an alteration in the balance between Th17 and Treg cells. To test this hypothesis we assessed fatigue in 30 stroke survivors using the Fatigue Scale for Motor and Cognitive Functions (FSMC. Peripheral blood was collected for assessment of Th17 and Treg cell populations and measurement of interleukin-10 (IL-10. Participants were dichotomized into severe fatigue n=14 and low-moderate fatigue n=16 groups by K-mean cluster analysis of FSMC scores. There were no group differences in age, gender, stroke type, stroke severity, or time since stroke. Stroke survivors in the severe fatigue group reported greater anxiety p=0.004 and depression p=0.001 than in the low-moderate fatigue group. The ratio of Th17 to Treg cells was significantly increased in the severe fatigue group relative to the mild-moderate fatigue group p=0.035. Serum levels of IL-10 negatively correlated withTh17/Treg ratio (r=-0.408,  p=0.025. Our preliminary findings suggest that an imbalance in the Th17/Treg ratio is associated with the severity of PSF.

Deletion of Fanca or Fancd2 dysregulates Treg in mice

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Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

2014-01-01

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

Deletion of Fanca or Fancd2 dysregulates Treg in mice.

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Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

2014-03-20

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

Selective Expansion of Memory CD4+ T cells By Mitogenic Human CD28 Generates Inflammatory Cytokines and Regulatory T cells

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Singh, Manisha; Basu, Sreemanti; Camell, Christina; Couturier, Jacob; Nudelman, Rodolfo J.; Medina, Miguel A.; Rodgers, John R.; Lewis, Dorothy E.

2009-01-01

Co-stimulatory signals are important for development of effector and regulatory T cells. In this case, CD28 signaling is usually considered inert in the absence of signaling through the TCR. By contrast, mitogenic rat CD28 mAbs reportedly expand regulatory T cells without TCR stimulation. We found that a commercially available human CD28 mAb (ANC28) stimulated PBMCs without TCR co-ligation or cross-linking; ANC28 selectively expanded CD4+CD25+FoxP3−(T effector) and CD4+CD25+FoxP3+ (Treg) cells. ANC28 stimulated the CD45RO+ CD4+ (memory) population whereas CD45RA+CD4+ (naïve) cells did not respond. ANC28 also induced inflammatory cytokines. Treg induced by ANC28 retain the Treg phenotype longer than did co-stimulated Treg. Treg induced by ANC28 suppressed CD25− T cells through a contact-dependent mechanism. Purity influenced the response of CD4+CD25+ cells because bead-purified CD4+CD25+ cells (85–90% pure) responded strongly to ANC28, whereas 98% pure FACS-sorted CD4+CD25 bright (T-reg) did not respond. Purified CD4+CD25int cells responded similarly to the bead-purified CD4+CD25+ cells. Thus, pre-activated CD4+ T cells (CD25int) respond to ANC28 rather than Treg (CD25bright). The ability of ANC28 to expand both effectors producing inflammatory cytokines as well as suppressive regulatory T cells might be useful for ex vivo expansion of therapeutic T cells. PMID:18446791

Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct

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Söderlund Johan

2010-08-01

Full Text Available Abstract Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir.

A rationale for the observed non-linearity in pressure tube creep sag with time in service

International Nuclear Information System (INIS)

Sedran, P.J.

2013-01-01

In 2012, a paper was presented at the CNS SGC Conference which included an explanation for measured non-linear trends in Pressure Tube (PT) creep sag. The section of the 2012 paper covering this topic was revised and is presented as the main subject of this paper. The practical applications for the prediction of long-term Fuel Channel (FC) creep sag include the analysis of Calandria Tube - Liquid Injection Nozzle (CT-LIN) contact, and fuel passage and PT replacement assessments. The current practice for predicting FC creep sag in life cycle management applications is to use a linear model for creep sag versus time in service. However, PT sag measurements from the Point Lepreau Generating Station (PLGS) and Gentilly-2 (G-2) have displayed a non-linear trend with a creep sag rate that is decreasing with time in service. As an example, for PT F06 in PLGS, a 60% reduction in the nominal creep sag rate was observed for measurements taken 18 years apart. Subsequently, it was found that a 56% reduction in the creep sag rate for F06 over 18 years could be attributed to a fundamental geometric property of the PT creep sag profile. In addition, a further 1.6% decrease in the creep sag rate of the CT over the same period could be attributed to bending stress reductions due to the deformation of the CT. The resultant reduction in the PT creep sag rate for F06 was predicted to be 57.6%, closely matching the observed PT creep sag rate reduction of 60%. Therefore, this paper provides a rationale to explain the observed non-linear trends in PT creep sag, the use of which could benefit stations engaging in asset management as a means of FC life extension. This paper presents a summary of the worked performed to correlate the observed reductions in PT creep sag rate to the geometrical properties of the PT creep sag profile and the predicted bending stress reductions in the CT. (author)

In-vitro inhibition of IFNγ+ iTreg mediated by monoclonal antibodies against cell surface determinants essential for iTreg function

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Daniel Volker

2012-08-01

Full Text Available Abstract Background IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins. Methods PBL of healthy control individuals were stimulated polyclonally in-vitro in the presence of monoclonal antibodies or recombinant proteins against/of CD178, CD152, CD279, CD28, CD95, and HLA-DR. Induction of IFNγ+ iTreg and proliferation of effector cells was determined using four-color fluorescence flow cytometry. Blockade of iTreg function was analyzed using polyclonally stimulated co-cultures with separated CD4+CD25+CD127-IFNγ+ PBL. Results High monoclonal antibody concentrations inhibited the induction of CD4+CD25+Foxp3+IFNγ+ PBL (anti-CD152, anti-CD279, anti-CD95: p +CD25+CD127-IFNγ+ PBL (anti-CD178, anti-CD152, anti-CD279, anti-CD95: p +CD25+Foxp3+IFNγ+ PBL (rCD152 and rCD95: p +CD25+CD127-IFNγ+ PBL showed lower cell proliferation than co-cultures with CD4+CD25+CD127-IFNγ- PBL (p +CD25+CD127-IFNγ- PBL-containing co-cultures in the presence of monoclonal antibody (anti-CD28, anti-CD152, anti-CD279: p +CD25+CD127-IFNγ+ PBL (with the exception anti-CD28 monoclonal antibody: p +CD25+CD127-IFNγ- PBL but do not efficiently block suppressive iTreg function in co-cultures with CD4+CD25+CD127-IFNγ+ PBL. Conclusions CD178, CD152, CD279, CD28, CD95, and HLA-DR determinants are important for induction and suppressive function of IFNγ+ iTreg.

Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg) Development.

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Zhou, Yuetao; Salker, Madhuri S; Walker, Britta; Münzer, Patrick; Borst, Oliver; Gawaz, Meinrad; Gulbins, Erich; Singh, Yogesh; Lang, Florian

2016-01-01

Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme involved in the production of ceramide by breaking down sphingomyelin. Previous studies in T-cells have suggested that ASM is involved in CD28 signalling, T lymphocyte granule secretion, degranulation, and vesicle shedding similar to the formation of phosphatidylserine-exposing microparticles from glial cells. However, whether ASM affects the development of Treg has not yet been described. Splenocytes, isolated Naive T lymphocytes and cultured T cells were characterized for various immune T cell markers by flow cytometery. Cell proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye, cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and protein expression by Western Blotting respectively. ASM deficient mice have higher number of Treg compared with littermate control mice. In vitro induction of ASM deficient T cells in the presence of TGF-β and IL-2 lead to a significantly higher number of Foxp3+ induced Treg (iTreg) compared with control T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation and Rictor levels compared with control iTreg. Ceramide C6 led to significant reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg leads to induction of IL-1β, IL-6 and IL-17 but not IFN-γ mRNA levels. ASM is a negative regulator of natural and iTreg. © 2016 The Author(s) Published by S. Karger AG, Basel.

Detection and correction for EPID and gantry sag during arc delivery using cine EPID imaging.

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Rowshanfarzad, Pejman; Sabet, Mahsheed; O'Connor, Daryl J; McCowan, Peter M; McCurdy, Boyd M C; Greer, Peter B

2012-02-01

Electronic portal imaging devices (EPIDs) have been studied and used for pretreatment and in-vivo dosimetry applications for many years. The application of EPIDs for dosimetry in arc treatments requires accurate characterization of the mechanical sag of the EPID and gantry during rotation. Several studies have investigated the effects of gravity on the sag of these systems but each have limitations. In this study, an easy experiment setup and accurate algorithm have been introduced to characterize and correct for the effect of EPID and gantry sag during arc delivery. Three metallic ball bearings were used as markers in the beam: two of them fixed to the gantry head and the third positioned at the isocenter. EPID images were acquired during a 360° gantry rotation in cine imaging mode. The markers were tracked in EPID images and a robust in-house developed MATLAB code was used to analyse the images and find the EPID sag in three directions as well as the EPID + gantry sag by comparison to the reference gantry zero image. The algorithm results were then tested against independent methods. The method was applied to compare the effect in clockwise and counter clockwise gantry rotations and different source-to-detector distances (SDDs). The results were monitored for one linear accelerator over a course of 15 months and six other linear-accelerators from two treatment centers were also investigated using this method. The generalized shift patterns were derived from the data and used in an image registration algorithm to correct for the effect of the mechanical sag in the system. The Gamma evaluation (3%, 3 mm) technique was used to investigate the improvement in alignment of cine EPID images of a fixed field, by comparing both individual images and the sum of images in a series with the reference gantry zero image. The mechanical sag during gantry rotation was dependent on the gantry angle and was larger in the in-plane direction, although the patterns were not

The negative temperature coefficient resistivities of Ag2S-Ag core–shell structures

International Nuclear Information System (INIS)

Yu, Mingming; Liu, Dongzhi; Li, Wei; Zhou, Xueqin

2014-01-01

In this paper, the conductivity of silver nanoparticle films protected by 3-mercaptopropionic acid (Ag/MPA) has been investigated. When the nanoparticles were annealed in air at 200 °C, they converted to stable Ag 2 S-Ag core–shell structures. The mechanism for the formation of the Ag 2 S-Ag core–shell structures along with the compositional changes and the microstructural evolution of the Ag/MPA nanoparticles during the annealing process are discussed. It is proposed that the Ag 2 S-Ag core–shell structure was formed through a solid-state reduction reaction, in which the Ag + ions coming from Ag 2 S were reduced by sulfonate species and sulfur ions. The final Ag 2 S-Ag films display an exponentially decreased resistivity with increasing temperature from 25 to 170 °C. The negative temperature coefficient resistivity of Ag 2 S-Ag films can be adjusted by changing the S/Ag molar ratio used for the synthesis of the Ag/MPA nanoparticles, paving the way for the preparation of negative temperature-coefficient thermistors via printing technology for use in the electronics.

Voltage Sag Compensator for CAR and SOR of HANARO

International Nuclear Information System (INIS)

Kim, Hyung-Kyoo; Jung, Hoan-Sung; Wu, Jong-Sup

2007-01-01

HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut-off rods(SOR) and the process systems, such as primary cooling system, secondary cooling system and reflector cooling system, etc., stop whenever the off-site power failure occurs, the reactor trips automatically. When voltage sag or momentary interruption occurs, the process systems are in operation but the reactor has an unwanted trip by insertion of CARs and SORs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent a nuisance trip. The compensated time is decided not to exceed 1 sec in consideration of reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis.

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Johan Verhagen

Full Text Available In vitro induced Foxp3+ T regulatory (iTreg cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.

Expansion of CD25-Negative Forkhead Box P3-Positive T Cells during HIV and Mycobacterium tuberculosis Infection

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Matías T. Angerami

2017-05-01

Full Text Available Tuberculosis (TB and HIV alter the immune system, and coinfected (HIV-TB individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of “unconventional” CD4+CD25−FoxP3+ Treg (uTreg population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4+CD25+FoxP3+ Treg subsets (cTreg in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1, glucocorticoid-induced tumor necrosis factor receptor (GITR, and the effector/memory distribution by flow cytometry in cTreg and uTreg. Also, IL-10, TGF-β, IFN-γ production, and the suppressor capacity of uTregs were analyzed in cocultures with effector lymphocytes and compared with the effect of regulatory T cells (Tregs. We found diminished expression of CD39 and higher levels of PD1 on uTreg compared to cTreg in both HIV-TB and healthy donors (HD. In addition, uTreg and cTreg showed differences in maturation status in both HIV-TB and HD groups, due to the expansion of effector memory uTregs. Interestingly, both HIV-TB and HD showed a pronounced production of IFN-γ in uTreg population, though no significant differences were observed for IL-10 and TGF-β production between uTreg and cTreg. Moreover, IFN-γ+ cells were restricted to the CD39− uTreg population. Finally, when the suppressor capacity was evaluated, both uTreg and cTreg inhibited polyclonal T cell-proliferation and IFN-γ production in a similar extent. These findings suggest that uTregs, which are expanded during HIV-TB coinfection, exert regulatory functions in a similar way to cTregs despite an altered surface expression of Treg characteristic markers and differences in cytokine production.

Allocation of Load-Loss Cost Caused by Voltage Sag

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Gao, X.

2017-10-01

This paper focuses on the allocation of load-loss cost caused by voltage sag in the environment of electricity market. To compensate the loss of loads due to voltage sags, the load-loss cost is allocated to both sources and power consumers. On the basis of Load Drop Cost (LDC), a quantitative evaluation index of load-loss cost caused by voltage sag is identified. The load-loss cost to be allocated to power consumers themselves is calculated according to load classification. Based on the theory of power component the quantitative relation between sources and loads is established, thereby a quantitative calculation method for load-loss cost allocated to each source is deduced and the quantitative compensation from individual source to load is proposed. A simple five-bus system illustrates the main features of the proposed method.

Immunogenic Eimeria tenella glycosylphosphatidylinositol-anchored surface antigens (SAGs induce inflammatory responses in avian macrophages.

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Yock-Ping Chow

Full Text Available At least 19 glycosylphosphatidylinositol (GPI-anchored surface antigens (SAGs are expressed specifically by second-generation merozoites of Eimeria tenella, but the ability of these proteins to stimulate immune responses in the chicken is unknown.Ten SAGs, belonging to two previously defined multigene families (A and B, were expressed as soluble recombinant (r fusion proteins in E. coli. Chicken macrophages were treated with purified rSAGs and changes in macrophage nitrite production, and in mRNA expression profiles of inducible nitric oxide synthase (iNOS and of a panel of cytokines were measured. Treatment with rSAGs 4, 5, and 12 induced high levels of macrophage nitric oxide production and IL-1β mRNA transcription that may contribute to the inflammatory response observed during E. tenella infection. Concomitantly, treatment with rSAGs 4, 5 and 12 suppressed the expression of IL-12 and IFN-γ and elevated that of IL-10, suggesting that during infection these molecules may specifically impair the development of cellular mediated immunity.In summary, some E. tenella SAGs appear to differentially modulate chicken innate and humoral immune responses and those derived from multigene family A (especially rSAG 12 may be more strongly linked with E. tenella pathogenicity associated with the endogenous second generation stages.

β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.

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Johnson, Mark C; Garland, Alaina L; Nicolson, Sarah C; Li, Chengwen; Samulski, R Jude; Wang, Bo; Tisch, Roland

2013-11-01

Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell-mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell-specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively suppresses ongoing type 1 diabetes long term.

The influence of transformers, induction motors and fault resistance regarding propagation voltage sags

OpenAIRE

Jairo Blanco; Ruben Darío Leal; Jonathan Jacome; Johann F. Petit; Gabriel Ordoñez; Víctor Barrera

2011-01-01

This article presents an analysis of voltage sag propagation. The ATPDraw tool was selected for simulating the IEEE 34 node test feeder. It takes into account both voltage sags caused by electrical fault network, as well as voltage sag propagation characteristics caused by induction motor starting and transformer energising. The analysis was aimed at assessing the influence of transformer winding connections, the impedance of these transformers, lines and cables, summarising the...

Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

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Wang, Xiaogang; Dong, Haisheng; Li, Qi; Li, Yingxian; Hong, An

2015-01-01

Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma. PMID:26405597

CARACTERIZACIÓN DE LUMINARIAS TIPO HALURO METÁLICO ANTE EVENTOS SAG

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Bonie Johana Restrepo Cuestas

Full Text Available Este artículo plantea una metodología para la caracterización de luminarias de haluro metálico, ante eventos sag. Inicialmente, se diseñó y construyó un generador de eventos sag. Luego, se planteó un esquema de pruebas, que fue utilizado para analizar el comportamiento de un tipo de luminarias de alta densidad de descarga tipo Metal Halide, ante eventos sag. Finalmente, tomando como referente el estándar SEMI F-47, se realizó la construcción de una curva característica que muestra la región de operación de la luminaria.

Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

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Slobodin, Gleb; Ahmad, Mohammad Sheikh; Rosner, Itzhak; Peri, Regina; Rozenbaum, Michael; Kessel, Aharon; Toubi, Elias; Odeh, Majed

2010-01-01

The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 2010 Elsevier Inc. All rights reserved.

Gravity sag of sandwich panel assemblies as applied to precision cathode strip chamber structural design

International Nuclear Information System (INIS)

Horvath, J.

1993-01-01

The relationship between gravity sag of a precision cathode strip chamber and its sandwich panel structural design is explored parametrically. An algorithm for estimating the dominant component of gravity sag is defined. Graphs of normalized gravity sag as a function of gap frame width and material, sandwich core edge filler width and material, panel skin thickness, gap height, and support location are calculated using the gravity sag algorithm. The structural importance of the sandwich-to-sandwich ''gap frame'' connection is explained

Improved detection of equine antibodies against Sarcocystis neurona using polyvalent ELISAs based on the parasite SnSAG surface antigens.

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Yeargan, Michelle R; Howe, Daniel K

2011-02-28

Equine protozoal myeloencephalitis (EPM) is a common neurologic disease of horses that is caused by the apicomplexan pathogen Sarcocystis neurona. To help improve serologic diagnosis of S. neurona infection, we have modified existing enzyme-linked immunosorbent assays (ELISAs) based on the immunogenic parasite surface antigens SnSAG2, SnSAG3, and SnSAG4 to make the assays polyvalent, thereby circumventing difficulties associated with parasite antigenic variants and diversity in equine immune responses. Two approaches were utilized to achieve polyvalence: (1) mixtures of the individual recombinant SnSAGs (rSnSAGs) were included in single ELISAs; (2) a collection of unique SnSAG chimeras that fused protein domains from different SnSAG surface antigens into a single recombinant protein were generated for use in the ELISAs. These new assays were assessed using a defined sample set of equine sera and cerebrospinal fluids (CSFs) that had been characterized by Western blot and/or were from confirmed EPM horses. While all of the polyvalent ELISAs performed relatively well, the highest sensitivity and specificity (100%/100%) were achieved with assays containing the rSnSAG4/2 chimera (Domain 1 of SnSAG4 fused to SnSAG2) or using a mixture of rSnSAG3 and rSnSAG4. The rSnSAG4 antigen alone and the rSnSAG4/3 chimera (Domain 1 of SnSAG4 fused to Domain 2 of SnSAG3) exhibited the next best accuracy at 95.2% sensitivity and 100% specificity. Binding ratios and percent positivity (PP) ratios, determined by comparing the mean values for positive versus negative samples, showed that the most advantageous signal to noise ratios were provided by rSnSAG4 and the rSnSAG4/3 chimera. Collectively, our results imply that a polyvalent ELISA based on SnSAG4 and SnSAG3, whether as a cocktail of two proteins or as a single chimeric protein, can give optimal results in serologic testing of serum or CSF for the presence of antibodies against S. neurona. The use of polyvalent SnSAG ELISAs will

SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region.

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Sun, Yun; Sun, Li; Xing, Ming-qing; Liu, Chun-sheng; Hu, Yong-hua

2013-11-12

Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to the immunoprotective mechanism

Cysticerci drive dendritic cells to promote in vitro and in vivo Tregs differentiation.

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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 CD25(high)Foxp3+ 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.

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

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Stockis, Julie; Liénart, Stéphanie; Colau, Didier; Collignon, Amandine; Nishimura, Stephen L; Sheppard, Dean; Coulie, Pierre G; Lucas, Sophie

2017-11-21

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis

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Fu, Wenyu; Hu, Wenhuo; Shi, Lei; Mundra, Jyoti Joshi; Xiao, GuoZhi; Dustin, Michael L.; Liu, Chuan-ju

2017-01-01

Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN. In addition, PGRN-mediated expansion and activation of Treg cells, as well as IL-10 production, depends on JNK signaling, but not on known PGRN-activated ERK and PI3K pathways. Furthermore, microarray and chromatin immunoprecipitation sequencing screens led to the discovery of forkhead box protein O4 and signal transducer and activator of transcription 3 as the transcription factors required for PGRN induction of IL-10 in Treg cells. These findings define a previously unrecognized signaling pathway that underlies IL-10 production by PGRN in Treg cells and present new insights into the mechanisms by which PGRN resolves inflammation in inflammatory conditions and autoimmune diseases, particularly inflammatory arthritis.—Fu, W., Hu, W., Shi, L., Mundra, J. J. Xiao, G., Dustin, M. L., Liu, C. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis. PMID:28011648

Multipurpose Compensation Scheme for Voltage Sag/Swell and Selective Harmonics Elimination in Distribution Systems

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Mustafa Inci

2018-01-01

Full Text Available Voltage harmonics, sag, and swell are the most harmful disturbances in distribution systems. This paper introduces a novel effective controller method for simultaneous compensation of both voltage sag/swell and voltage harmonics by using multifunctional dynamic voltage restorer. In proposed controller method called FFT with integrated ISRF, ISRF detects the magnitudes of voltage sag/swell quickly and precisely, and FFT extracts the selective components of voltage harmonics very effectively. The proposed method integrates the superior properties of ISRF and FFT methods. FFT integrated ISRF is applied for the first time to provide the compensation of both sag/swell and selective harmonics together. The proposed system has ability to compensate symmetrical/asymmetrical sag/swell and symmetrical/asymmetrical selective harmonics which are 5th, 7th, 11th and 13th. The controlled system is modelled in PSCAD/EMDTC and compared with conventional methods. The performance results verify that the proposed method compensates voltage disturbances effectively in the system.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

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Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

2013-02-08

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

International Nuclear Information System (INIS)

Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

2013-01-01

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17.

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Zhang, Lingling; Fu, Jingjing; Sheng, Kangliang; Li, Ying; Song, Shanshan; Li, Peipei; Song, Shasha; Wang, Qingtong; Chen, Jingyu; Yu, Jianhua; Wei, Wei

2015-03-01

Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+) DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17 function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic potential for autoimmune arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

Downregulation of IL-17-producing T cells is associated with regulatory T cell expansion and disease progression in chronic lymphocytic leukemia.

Science.gov (United States)

Jadidi-Niaragh, Farhad; Ghalamfarsa, Ghasem; Memarian, Ali; Asgarian-Omran, Hossein; Razavi, Seyed Mohsen; Sarrafnejad, Abdolfattah; Shokri, Fazel

2013-04-01

Little is known about the immunobiology of interleukin-17 (IL-17)-producing T cells and regulatory T cells (Treg) in chronic lymphocytic leukemia (CLL). In this study, the frequencies of Th17, Tc17, and CD39(+) Treg cells were enumerated in peripheral T cells isolated from 40 CLL patients and 15 normal subjects by flow cytometry. Our results showed a lower frequency of Th17 and Tc17 cells in progressive (0.99 ± 0.12 % of total CD3(+)CD4(+) cells; 0.44 ± 0.09 % of total CD8(+) cells) compared to indolent patients (1.57 ± 0.24 %, p = 0.042; 0.82 ± 0.2 %, p = 0.09) and normal subjects (1.78 ± 0.2 %, p = 0.003; 0.71 ± 0.09 %, p = 0.04). Decrease in IL-17-producing T cells was associated with CD39(+) Treg cells expansion. Variation of IL-17-producing cells and Treg cells in indolent and progressive patients was neither associated to the expression levels of Th1- and Th2-specific transcription factors T-bet and GATA-3 nor to the frequencies of IFN-γ and IL-4-producing CD4(+) T cells in a selected number of samples. Additionally, suppressive potential of CD4(+) Treg was similar in CLL patients and normal subjects. Our data indicate that progression of CLL is associated with downregulation of IL-17-producing T cells and expansion of Treg cells, implying contribution of these subsets of T cells in the progression of CLL.

The SnSAG merozoite surface antigens of Sarcocystis neurona are expressed differentially during the bradyzoite and sporozoite life cycle stages.

Science.gov (United States)

Gautam, A; Dubey, J P; Saville, W J; Howe, D K

2011-12-29

Sarcocystis neurona is a two-host coccidian parasite whose complex life cycle progresses through multiple developmental stages differing at morphological and molecular levels. The S. neurona merozoite surface is covered by multiple, related glycosylphosphatidylinositol-linked proteins, which are orthologous to the surface antigen (SAG)/SAG1-related sequence (SRS) gene family of Toxoplasma gondii. Expression of the SAG/SRS proteins in T. gondii and another related parasite Neospora caninum is life-cycle stage specific and seems necessary for parasite transmission and persistence of infection. In the present study, the expression of S. neurona merozoite surface antigens (SnSAGs) was evaluated in the sporozoite and bradyzoite stages. Western blot analysis was used to compare SnSAG expression in merozoites versus sporozoites, while immunocytochemistry was performed to examine expression of the SnSAGs in merozoites versus bradyzoites. These analyses revealed that SnSAG2, SnSAG3 and SnSAG4 are expressed in sporozoites, while SnSAG5 was appeared to be downregulated in this life cycle stage. In S. neurona bradyzoites, it was found that SnSAG2, SnSAG3, SnSAG4 and SnSAG5 were either absent or expression was greatly reduced. As shown for T. gondii, stage-specific expression of the SnSAGs may be important for the parasite to progress through its developmental stages and complete its life cycle successfully. Thus, it is possible that the SAG switching mechanism by these parasites could be exploited as a point of intervention. As well, the alterations in surface antigen expression during different life cycle stages may need to be considered when designing prospective approaches for protective vaccination. Copyright © 2011 Elsevier B.V. All rights reserved.

Appropriate Development of the Liver Treg Compartment Is Modulated by the Microbiota and Requires TGF-β and MyD88

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Ann Maria

2014-01-01

Full Text Available Neither the early postnatal development of the liver Treg compartment nor the factors that regulate its development has been characterized. We compared the early developmental patterns of Treg cell accumulation in murine liver, thymus, and spleen. A FoxP3EGFP reporter mouse was employed to identify Treg cells. Mononuclear cells were isolated from organs postnatally, stained for CD4, and examined by flow cytometry to enumerate FoxP3+CD4hi cells. To assess roles for TGF-β1, MyD88, and TLR2, gene-specific knockout pups were generated from heterozygous breeders. To test the role of commensal bacteria, pregnant dams were administered antibiotics during gestation and after parturition. The pattern of appearance of Treg cells differed in liver, spleen, and thymus. Notably, at 1-2 weeks, the frequency of CD4hi FoxP3+ T cells in liver exceeded that in spleen by 1.5- to 2-fold. The relative increase in liver Treg frequency was transient and was dependent upon TGF-β1 and MyD88, but not TLR2, and was abrogated by antibiotic treatment. A relative increase in liver Treg frequency occurs approximately 1-2 weeks after parturition that appears to be driven by colonization of the intestine with commensal bacteria and is mediated by a pathway that requires TGF-β1 and MyD88, but not TLR2.

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

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Laura Adalid-Peralta

2013-01-01

Full Text Available 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.

Regulatory T cells (Treg and Their Roles in Immune System with Respect to Immunopathological Disorders

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Kateřina Kondělková

2010-01-01

Full Text Available Regulatory T cells (Tregs are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density and CD127low (low molecular density could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.

Antigenic evaluation of a recombinant baculovirus-expressed Sarcocystis neurona SAG1 antigen.

Science.gov (United States)

Gupta, G D; Lakritz, J; Saville, W J; Livingston, R S; Dubey, J P; Middleton, J R; Marsh, A E

2004-10-01

Sarcocystis neurona is the primary parasite associated with equine protozoal myeloencephalitis (EPM). This is a commonly diagnosed neurological disorder in the Americas that infects the central nervous system of horses. Current serologic assays utilize culture-derived parasites as antigen. This method requires large numbers of parasites to be grown in culture, which is labor intensive and time consuming. Also, a culture-derived whole-parasite preparation contains conserved antigens that could cross-react with antibodies against other Sarcocystis species and members of Sarcocystidae such as Neospora spp., Hammondia spp., and Toxoplasma gondii. Therefore, there is a need to develop an improved method for the detection of S. neurona-specific antibodies. The sera of infected horses react strongly to surface antigen 1 (SnSAG1), an approximately 29-kDa protein, in immunoblot analysis, suggesting that it is an immunodominant antigen. The SnSAG1 gene of S. neurona was cloned, and recombinant S. neurona SAG1 protein (rSnSAG1-Bac) was expressed with the use of a baculovirus system. By immunoblot analysis, the rSnSAG1-Bac antigen detected antibodies to S. neurona from naturally infected and experimentally inoculated equids, cats, rabbit, mice, and skunk. This is the first report of a baculovirus-expressed recombinant S. neurona antigen being used to detect anti-S. neurona antibodies in a variety of host species.

Modelling of V-Hz and vector controlled ASDs in PSCAD/EMTDC for voltage sag studies

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Vegunta, S.C. [TNEI Services Ltd, Manchester M1 2PW (United Kingdom); Milanovic, J.V. [School of Electrical and Electronic Engineering of The University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom); Djokic, S.Z. [School of Engineering of The University of Edinburgh, The King' s Buildings, Mayfield Road, Edinburgh EH9 3JL (United Kingdom)

2010-01-15

This paper deals with modelling and performance of adjustable speed drives (ASDs) subjected to voltage disturbances in electric supply. The aim of this study was to develop appropriate models of typical ASD and investigate their sensitivity to voltage disturbances under various practical modes of operation and control. Accordingly, scalar controlled open and closed loop volts-hertz (V-Hz) and vector controlled closed loop ASDs are modelled in PSCAD/EMTDC environment, and their performance in the presence of voltage disturbances is investigated under typical operating and loading conditions. The drive sensitivity to three-phase, two-phase and single-phase voltage sags and short interruptions was assessed, and the findings are discussed in the paper. Depending on the type of drive control, type of voltage sag, applied load torque and adjusted speed, various sensitivity curves were established and analyzed. (author)

Salivary agglutinin/DMBT1SAG expression is up-regulated in the presence of salivary gland tumors

DEFF Research Database (Denmark)

Bikker, F J; van der Wal, J E; Ligtenberg, A J M

2004-01-01

Salivary agglutinin (SAG) is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1) and represents the salivary variant of DMBT1 (DMBT1(SAG)). While SAG is a bona fide anti-caries factor, DMBT1 was proposed as a candidate tumor-suppressor for brain, digestive tract, and lung cancer. Thou...

Human Tregs Made Antigen Specific by Gene Modification: The Power to Treat Autoimmunity and Antidrug Antibodies with Precision

Directory of Open Access Journals (Sweden)

Patrick R. Adair

2017-09-01

Full Text Available Human regulatory CD4+ T cells (Tregs are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII. Seminal clinical trials have used polyclonal Tregs, but the frequency of antigen-specific Tregs among polyclonal populations is low, and polyclonal Tregs may risk non-specific immunosuppression. Antigen-specific Treg therapy, which uses genetically modified Tregs expressing receptors specific for target antigens, greatly mitigates this risk. Building on the principles of T-cell receptor cloning, chimeric antigen receptors (CARs, and a novel CAR derivative, called B-cell antibody receptors, our lab has developed different types of antigen-specific Tregs. This review discusses the current research and optimization of gene-modified antigen-specific human Tregs in our lab in several disease models. The preparations and considerations for clinical use of such Tregs also are discussed.

Early Prediction of Transient Voltage Sags caused by Rotor Swings

DEFF Research Database (Denmark)

Weckesser, Johannes Tilman Gabriel; Jóhannsson, Hjörtur; Van Cutsem, Thierry

2014-01-01

The paper investigates various methods to predict voltage sags at load buses caused by large generator rotor swings and following a transient disturbance. Three different prediction methods are proposed, which all use real-time measurements from PMUs. One of the methods uses a slightly extended v...... version of the E-SIME method. The other two methods use Measurements and process them by recursive least square estimation. It is shown that the prediction method employing E-SIME allows the earliest detection of a critical voltage sag with satisfactory accuracy....

The Early Cambrian Mianyang-Changning Intracratonic Sag and Its Control on Petroleum Accumulation in the Sichuan Basin, China

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Shugen Liu

2017-01-01

Full Text Available The older and deeper hydrocarbon accumulations receive increasing attention across the world, providing more technical and commercial challenges to hydrocarbon exploration. We present a study of an asymmetrical, N-S striking intracratonic sag which developed across the Sichuan basin, south China, from Late Ediacaran to Early Cambrian times. The Mianyang-Changning intracratonic sag is ~50 km wide, with its steepest part in the basin center. In particular the eastern margin shows its greatest steepness. Five episodes in the evolutions of the sag can be recognized. It begins in the Late Ediacaran with an uplift and erosion correlated to Tongwan movement. Initial extension occurred during the Early Cambrian Maidiping period, when more strata of the Maidiping Formation were deposited across the sag. Subsequently, maximum extension occurred during the Early Cambrian Qiongzhusi period that resulted in 450–1700 m thick Maidiping-Canglangpu Formations being deposited in the sag. Then, the sag disappeared at the Longwangmiao period, as it was infilled by the sediments. The intracratonic sag has significant influence on the development of high-quality reservoirs in the Dengying and Longwangmiao Formations and source-rock of the Niutitang Formation. It thus indicates that a high probability for oil/gas accumulation exists along the intracratonic sag, across the central Sichuan basin.

IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154–CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice

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Dela Golshayan

2017-04-01

Full Text Available In recent years, regulatory T cells (Treg-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT. However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells. IL-2-mediated Treg expansion in combination with short-term CD154–CD40 co-stimulation blockade, but not CTLA-4 Ig or rapamycin, led to tolerance to MHC-mismatched skin grafts in non-lymphopenic mice, mainly by hindering alloreactive CD8+ effector T cells and the production of alloantibodies. Importantly, this treatment also allowed prolonged survival of allografts in the presence of either donor-specific or cross-reactive memory cells. However, late rejection occurred in sensitized hosts, partly mediated by activated B cells. Overall, these data illustrate the potential but also some important limitations of Treg-based therapy in clinical SOT as well as the importance of concomitant immunomodulatory strategies in particular in sensitized hosts.

A new trivalent SnSAG surface antigen chimera for efficient detection of antibodies against Sarcocystis neurona and diagnosis of equine protozoal myeloencephalitis.

Science.gov (United States)

Yeargan, Michelle; de Assis Rocha, Izabela; Morrow, Jennifer; Graves, Amy; Reed, Stephen M; Howe, Daniel K

2015-05-01

Enzyme-linked immunosorbent assays (ELISAs) based on the SnSAG surface antigens of Sarcocystis neurona provide reliable detection of infection by the parasite. Moreover, accurate serodiagnosis of equine protozoal myeloencephalitis (EPM) is achieved with the SnSAG ELISAs by measuring antibodies in serum and cerebrospinal fluid (CSF) to reveal active infection in the central nervous system. Two independent ELISAs based on recombinant (r)SnSAG2 or a chimeric fusion of SnSAG3 and SnSAG4 (rSnSAG4/3) are currently used together for EPM serodiagnosis to overcome varied antibody responses in different horses. To achieve reliable antibody detection with a single ELISA instead of 2 separate ELISAs, rSnSAG2 was fused with rSnSAG4/3 into a single trivalent protein, designated rSnSAG2/4/3. Paired serum and CSF from 163 horses were tested with all 3 ELISAs. When the consensus antibody titers obtained with the rSnSAG2 and rSnSAG4/3 ELISAs were compared to the single SAG2/4/3 ELISA titers, Spearman rank correlation coefficients of ρ = 0.74 and ρ = 0.90 were obtained for serum and CSF, respectively, indicating strong agreement between the tests. When the rSnSAG2 and rSnSAG4/3 consensus serum-to-CSF titer ratio was compared to the rSnSAG2/4/3 serum-to-CSF titer ratio, the Spearman correlation coefficient was ρ = 0.87, again signifying strong agreement. Importantly, comparing the diagnostic interpretation of the serum-to-CSF titer ratios yielded a Cohen kappa value of 0.77. These findings suggest that the single ELISA based on the trivalent rSnSAG2/4/3 will provide serologic and diagnostic results that are highly comparable to the consensus of the 2 independent ELISAs based on rSnSAG2 and rSnSAG4/3. © 2015 The Author(s).

Clinical-Grade-Expanded Regulatory T Cells Prevent Graft-versus-Host Disease While Allowing a Powerful T Cell-Dependent Graft-versus-Leukemia Effect in Murine Models.

Science.gov (United States)

Del Papa, Beatrice; Ruggeri, Loredana; Urbani, Elena; Baldoni, Stefano; Cecchini, Debora; Zei, Tiziana; Iacucci Ostini, Roberta; Crescenzi, Barbara; Carotti, Alessandra; Pierini, Antonio; Sportoletti, Paolo; Di Bartolomeo, Paolo; Falzetti, Franca; Mecucci, Cristina; Velardi, Andrea; Martelli, Massimo F; Di Ianni, Mauro

2017-11-01

We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong Mixed Lymphocytes Reaction inhibition. In vitro amplification did not induce any karyotypic modification. To evaluate the graft-versus-host disease (GVHD)/graft-versus-leukemia (GVL) bifunctional axis, expanded Tregs and conventional T cells (Tcons) were tested in NOD/SCID/IL2Rgnull mice injected with primary acute myeloid leukemia (AML) cells, AML cell line, acute lymphoid leukemia Philadelphia cell line, or Burkitt-like lymphoma cell line. All mice that received leukemia cells together with expanded Tregs and Tcons were rescued from leukemia and survived without GVHD, showing that Treg expansion procedure did not compromise GVHD control and the strong Tcon-mediated GVL activity. This report might represent the basis for treating high-risk leukemia and/or relapsed/refractory leukemia patients with high-dose Treg/Tcons. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice.

Science.gov (United States)

D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A; Mathis, Diane; Benoist, Christophe

2011-05-24

Foxp3(+) regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4(+) T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility.

TGF-β induces the expression of Nedd4 family-interacting protein 1 (Ndfip1) to silence IL-4 production during iTreg cell differentiation

Science.gov (United States)

Beal, Allison M.; Ramos-Hernández, Natalia; Riling, Chris R.; Nowelsky, Erin A.; Oliver, Paula M.

2011-01-01

Mice deficient for the adaptor Ndfip1 develop inflammation at sites of environmental antigen exposure. We show here that these animals contain fewer inducible regulatory (iTreg) cells. In vitro, Ndfip1-deficient T cells express normal levels of the transcription factor Foxp3 during the first 48 hours of iTreg cell differentiation, however this cannot be sustained. Abortive Foxp3 expression is because Ndfip1–/– cells produce interleukin 4 (IL-4). We demonstrate that Ndfip1 is transiently unregulated during iTreg cell differentiation in a transforming growth factor-β (TGF-β) dependent manner. Once expressed Ndfip1 promotes Itch-mediated degradation of the transcription factor JunB, thus preventing IL-4 production. Based on these data, we propose that TGF-β signaling induces Ndfip1 expression to silence IL-4 production, thus permitting iTreg cell differentiation. PMID:22080920

CD11c-expressing cells affect Treg behavior in the meninges during CNS infection1

Science.gov (United States)

O’Brien, Carleigh A.; Overall, Christopher; Konradt, Christoph; O’Hara Hall, Aisling C.; Hayes, Nikolas W.; Wagage, Sagie; John, Beena; Christian, David A.; Hunter, Christopher A.; Harris, Tajie H.

2017-01-01

Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c+ cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c+ populations regulates their local behavior during T. gondii infection. PMID:28389591

The sagging rope sign in achondroplasia - different from Perthes' disease

International Nuclear Information System (INIS)

Shingade, Viraj U.; Song, Hae-Ryong; Lee, Seok-Hyun; Suh, Seung-Woo; Oh, Chang-Wug; Hong, Jun-Seok

2006-01-01

The sagging rope sign is a radio-opaque line, seen on radiographs of the hips, with Perthes' disease. The main purpose of this study was to determine the incidence, cause and importance of this sign in achondroplasia, and to reveal how it differs from in Perthes' disease. Serial radiograms, along with 2-dimensional and 3-dimensional CT images were studied in 42 achondroplasic patients. Forty-two achondroplasic patients, reported at our institute (for routine outpatient consultation, spine surgeries, deformity corrections, limb-lengthening procedures) were included in this study. There were 26 males and 16 females. The sign was observed bilaterally, in all patients. Evaluation of CT images revealed spherical heads, with presence of circumferential overhang in all hips. This circumferential overhang, seen on 3-D CT scan, corresponded to the sagging rope sign on radiographs. Presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from Perthes' disease, and its presence does not carry a bad prognosis in achondroplasia. (orig.)

Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells

International Nuclear Information System (INIS)

Kim, Joon-Young; Kim, Han-Jong; Hurt, Elaine M.; Chen, Xin; Howard, O.M. Zack; Farrar, William L.

2007-01-01

FOXP3, a forkhead transcription factor is essential for the development and function of CD4 + CD25 + regulatory T cells (Tregs). In contrast to conversion of murine naive T cells to Tregs by transduction of Foxp3, it is controversial whether ectopic expression of FOXP3 in human CD4 + T cells is sufficient for acquisition of suppressive activity. Here, we show that retroviral transduction of FOXP3 induces a Treg phenotype in human leukemic CD4 + Jurkat-T cells, evidenced by increased expression of Treg-associated cell surface markers as well as inhibition of cytokine production. Furthermore, FOXP3-transduced Jurkat-T cells suppress the proliferation of human CD4 + CD25 - T cells. Additionally, DNA microarray analysis identifies Treg-related genes regulated by FOXP3. Our study demonstrates that enforced expression of FOXP3 confers Treg-like properties on Jurkat-T cells, which can be a convenient and efficient Treg-like cell model for further study to identify Treg cell surface markers and target genes regulated by FOXP3

Synthesis, morphological control, and antibacterial properties of hollow/solid Ag2S/Ag heterodimers

KAUST Repository

Pang, Maolin; Hu, Jiangyong; Zeng, Huachun

2010-01-01

of this highly asymmetric dipolar composite, photocatalytic inactivation of Escherichia coli K-12 in the presence of the as-prepared Ag 2S/Ag heterodimers has been carried out under UV irradiation. The added Ag2S/Ag heterodimers show good chemical stability under

Foxp3 regulates ratio of Treg and NKT cells in a mouse model of asthma.

Science.gov (United States)

Lu, Yanming; Guo, Yinshi; Xu, Linyun; Li, Yaqin; Cao, Lanfang

2015-05-01

Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFβ1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma.

A novel current mode controller for a static compensator utilizing Goertzel algorithm to mitigate voltage sags

International Nuclear Information System (INIS)

Najafi, E.; Yatim, A.H.M.

2011-01-01

Research highlights: → We proposed a new current control method for STATCOM. → The current control method maintains a fixed switching frequency. → It also produces fewer harmonics compared to conventional hysteresis method. → A new voltage dip (sag) detection method was used in STATCOM. → The control method can mitigate voltage sag in each phase separately. -- Abstract: Static compensator (STATCOM) has been widely proposed for power quality and network stability improvement. It is easily connected in parallel to the electric network and has many advantages for electrical grids. It can improve network stability; power factor, power transfer rating and can avoid some disturbances such as sags and swells. Most of STATCOM controllers are based on voltage controllers that are based on balanced d-q transform. However, they are not thorough solutions for network disturbances since in most cases single-phase disturbances occur in electrical networks that cannot be avoided by the conventional controllers. Voltage mode controllers are also not capable of responding fast enough to the changes expected of a network system. This paper proposes a new current mode controller to overcome the mentioned problem. The approach uses a fixed frequency current controller to maintain voltage levels in voltage sags (dips). This approach is also simple and can be easily implemented by digitally. It has superior performance over conventional methods in terms of harmonic reduction in STATCOM output current. Another important factor for STATCOM effectiveness in sag mitigation is its sag detection method. This paper also introduces a new sag detection method based on Goertzel algorithm which is both effective and simple for practical applications. The simulation results presented illustrate the superiority of the proposed controller and sag detection algorithm to be utilized in the STATCOM.

Measurement and computation for sag of calandria tube due to irradiation creep in PHWR

International Nuclear Information System (INIS)

Son, S. M.; Lee, W. R.; Lee, S. K.; Lee, J. S.; Kim, T. R.; Na, B. K.; Namgung I.

2003-01-01

Calandria tubes and Liquid Injection Shutdown System(LISS) tubes in a Pressurized Heavy Water Reactor(PHWR) are to sag due to irradiation creep and growth during plant operation. When the sag of calandria tube becomes bigger, the calandria tube possibly comes in contact with LISS tube crossing beneath the calandria tube. The contact subsequently may cause the damage on the calandria tube resulting in unpredicted outage of the plant. It is therefore necessary to check the gap between the two tubes in order to periodically confirm no contact by using a proper measure during the plant life. An ultrasonic gap measuring probe assembly which can be inserted into two viewing ports of the calandria was developed in Korea and utilized to measure the sags of both tubes in the PHWR. It was found that the centerlines of calandria tubes and liquid injection shutdown system tubes can be precisely detected by ultrasonic wave. The gaps between two tubes were easily obtained from the relative distance of the measured centerline elevations of the tubes. Based on the irradiation creep equation and the measurement data, a computer program to calculate the sags was also developed. With the computer program, the sag at the end of plant life was predicted

The Correlation of Regulatory T (TReg and Vitamin D3 in Pediatric Nephrotic Syndrome

Directory of Open Access Journals (Sweden)

Yunika Nurtyas

2018-01-01

Full Text Available Nephrotic syndrome (NS is an autoimmune disease that correlates to the imbalance of regulatory T cells (TReg. This study was aimed to investigate the effect of vitamin D as adjuvant therapy of TReg population in pediatric nephrotic syndrome. This study was designed randomized clinical trial, double blind, with pre- and post-test control groups involving 15 subjects newly diagnosed with NS. Subjects were divided into 2 groups, namely K1 for group treated with prednisone+vitamin D and K2 group for prednisone treatment only. The population of TReg in peripheral blood mononuclear cells (PBMC was analyzed using flowcytometry. Vitamin D serum level was measured through ELISA method. Results showed that there was a significant elevation of TReg (independent t-test, p = 0.010 in K1 group, which was higher than in K2 group. The Pearson test in the K1 group showed that vitamin D level was positively correlated with TReg (p = 0.039, r = 0.779.

Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

KAUST Repository

Schmidt, Angelika

2018-04-27

BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.ResultsTo gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.ConclusionThe data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

Strains of Sarcocystis neurona exhibit differences in their surface antigens, including the absence of the major surface antigen SnSAG1.

Science.gov (United States)

Howe, Daniel K; Gaji, Rajshekhar Y; Marsh, Antoinette E; Patil, Bhagyashree A; Saville, William J; Lindsay, David S; Dubey, J P; Granstrom, David E

2008-05-01

A gene family of surface antigens is expressed by merozoites of Sarcocystis neurona, the primary cause of equine protozoal myeloencephalitis (EPM). These surface proteins, designated SnSAGs, are immunodominant and therefore excellent candidates for development of EPM diagnostics or vaccines. Prior work had identified an EPM isolate lacking the major surface antigen SnSAG1, thus suggesting there may be some diversity in the SnSAGs expressed by different S. neurona isolates. Therefore, a bioinformatic, molecular and immunological study was conducted to assess conservation of the SnSAGs. Examination of an expressed sequence tag (EST) database revealed several notable SnSAG polymorphisms. In particular, the EST information implied that the EPM strain SN4 lacked the major surface antigen SnSAG1. The absence of this surface antigen from the SN4 strain was confirmed by both Western blot and Southern blot. To evaluate SnSAG polymorphisms in the S. neurona population, 14 strains were examined by Western blots using monospecific polyclonal antibodies against the four described SnSAGs. The results of these analyses demonstrated that SnSAG2, SnSAG3, and SnSAG4 are present in all 14 S. neurona strains tested, although some variance in SnSAG4 was observed. Importantly, SnSAG1 was not detected in seven of the strains, which included isolates from four cases of EPM and a case of fatal meningoencephalitis in a sea otter. Genetic analyses by PCR using gene-specific primers confirmed the absence of the SnSAG1 locus in six of these seven strains. Collectively, the data indicated that there is heterogeneity in the surface antigen composition of different S. neurona isolates, which is an important consideration for development of serological tests and prospective vaccines for EPM. Furthermore, the diversity reported herein likely extends to other phenotypes, such as strain virulence, and may have implications for the phylogeny of the various Sarcocystis spp. that undergo sexual stages

A cluster of coregulated genes determines TGF-β–induced regulatory T-cell (Treg) dysfunction in NOD mice

Science.gov (United States)

D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe

2011-01-01

Foxp3+ regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4+ T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility. PMID:21543717

Cloning and characterisation of the sagA gene of Aspergillus nidulans: a gene which affects sensitivity to DNA-damaging agents.

Science.gov (United States)

Jones, G W; Hooley, P; Farrington, S M; Shawcross, S G; Iwanejko, L A; Strike, P

1999-03-01

Mutations within the sagA gene of Aspergillus nidulans cause sensitisation to DNA-damaging chemicals but have no effect upon spontaneous or damage-induced mutation frequency. The sagA gene was cloned on a 19-kb cosmid-derived fragment by functional complementation of a sagA1 sagC3 double mutant; subsequently, a fragment of the gene was also isolated on a 3.9-kb genomic subclone. Initial sequencing of a small section of the 19-kb fragment allowed the design of primers that were subsequently used in RTPCR experiments to show that this DNA is transcribed. A 277-bp fragment derived from the transcribed region was used to screen an A. nidulans cDNA library, resulting in the isolation of a 1.4-kb partial cDNA clone which had sequence overlap with the genomic sagA fragment. This partial cDNA was incomplete but appeared to contain the whole coding region of sagA. The sagA1 mutant was shown to possess two mutations; a G-T transversion and a+ 1 frameshift due to insertion of a T. causing disruption to the C-terminal region of the SagA protein. Translation of the sagA cDNA predicts a protein of 378 amino acids, which has homology to the Saccharomyces cerevisiae End3 protein and also to certain mammalian proteins capable of causing cell transformation.

Mitigation of Voltage Sags in CIGRE Low Voltage Distribution Network

DEFF Research Database (Denmark)

Mustafa, Ghullam; Bak-Jensen, Birgitte; Mahat, Pukar

2013-01-01

Any problem in voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM), Dynamic Voltage Restorer (DVR) etc. are commonly used for the mitigation of voltage p....... The compensation of voltage sags in the different parts of CIGRE distribution network is done by using the four STATCOM compensators already existing in the test grid. The simulations are carried out in DIgSILENT power factory software version 15.0.......Any problem in voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM), Dynamic Voltage Restorer (DVR) etc. are commonly used for the mitigation of voltage...... problems in the distribution system. The voltage problems dealt with in this paper are to show how to mitigate voltage sags in the CIGRE Low Voltage (LV) test network and networks like this. The voltage sags, for the tested cases in the CIGRE LV test network are mainly due to three phase faults...

Complete characterization of voltage sags: an alternative to achieve energy quality

International Nuclear Information System (INIS)

Zuniga Medina, Edgar Andres; Vasco Garcia, Carlos Andres

1992-01-01

In this paper, the meaning of the power quality and its negative influence in the automation processes are presented. Voltage sags, the problems they cause and a methodology to characterize the phenomenon are also presented. Once the problems associated with the different sensible loads connected to a power system are identified, the cause of the bad quality of the electrical energy provided those loads is then established; voltage sags are one of the most common phenomenon that requires characterization in order to diminish their negative impact on the industrial processes

La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino Regulatory T cell depletion increases the number of CD8 cells during mouse mammary tumor virus infection

Directory of Open Access Journals (Sweden)

Gabriel Cabrera

2011-06-01

Full Text Available El virus del tumor mamario murino (MMTV es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg CD4+CD25+Foxp3+ específicas para el superantígeno (Sag viral en las placas de Peyer (PP. En este trabajo se evaluó si la depleción de las células Treg influencia la población de células CD8+ durante la infección con MMTV a través del amamantamiento. La depleción de las células Treg al día 6 de infección causó incrementos en el porcentaje y número absoluto de las células CD8+ en los ganglios y provocó un incremento en la intensidad de fluorescencia media del marcador de activación CD44 en esas células. Los incrementos en el número absoluto de las células CD8 se observaron en células con cadenas variables Vβ del receptor de las células T (TCR tanto reactivas como no reactivas al Sag. Previamente habíamos demostrado que la depleción de las células Treg al día 6 de infección disminuye la carga viral. Los resultados presentados en este trabajo sugieren que, al menos a partir del día 6 de infección con MMTV, las células Treg podrían tener un rol inhibiendo la generación de una respuesta CD8 antiviral.Mouse mammary tumor virus (MMTV is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. We have shown in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (Sag-specific CD4+ CD25+ Foxp3+ regulatory T cells (Treg in Peyer's patches. Herein, we evaluated whether the depletion of Treg cells affects the CD8+ population during milk-borne MMTV infection. At day 6 of infection, the depletion of Treg cells increased the percentage and absolute number of CD8+ cells in lymph nodes as well as the

Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

Directory of Open Access Journals (Sweden)

Sutmuller Roger PM

2011-03-01

Full Text Available Abstract Background Regulatory T cells (Treg play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2 agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff cells and dendritic cells (DCs individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.

Synthesis, morphological control, and antibacterial properties of hollow/solid Ag2S/Ag heterodimers

KAUST Repository

Pang, Maolin

2010-08-11

Ag2S and Ag are important functional materials that have received considerable research interest in recent years. In this work, we develop a solution-based synthetic method to combine these two materials into hollow/solid Ag2S/Ag heterodimers at room temperature. Starting from monodisperse Cu2O solid spheres, CuS hollow spheres can be converted from Cu2O through a modified Kirkendall process, and the obtained CuS can then be used as a solid precursor for preparation of the Ag2S/Ag heterodimers through ion exchange and photo-assisted reduction. We have found that formation of the Ag2S/Ag heterodimers is instantaneous, and the size of Ag nanocrystals on the hollow spheres of Ag2S can be controlled by changing the concentration and power of reducing agents in the synthesis. The growth of Ag nanoparticles on hollow spheres of Ag2S in the dimers is along the [111] direction of the silver crystal; the light absorption properties have also been investigated. Furthermore, coupling or tripling of Ag2S/Ag heterodimers into dumbbell-like trimers ((Ag 2S)2/Ag, linear) and triangular tetramers ((Ag 2S)3/Ag, coplanar) can also be attained at 60°C by adding the bidentate ligand ethylenediamine as a cross-linking agent. To test the applicability of this highly asymmetric dipolar composite, photocatalytic inactivation of Escherichia coli K-12 in the presence of the as-prepared Ag 2S/Ag heterodimers has been carried out under UV irradiation. The added Ag2S/Ag heterodimers show good chemical stability under prolonged UV irradiation, and no appreciable solid dissolution is found. Possible mechanisms regarding the enhanced antibacterial activity have also been addressed. © 2010 American Chemical Society.

Experimental testing of a SAG digital SILT application

International Nuclear Information System (INIS)

Haapanen, P.; Maskuniitty, M.; Heikkinen, J.; Korhonen, J.

1995-10-01

A prototype dynamic testing harness for programmable automation systems has been specified and implemented at the Technical Research Centre of Finland (VTT). In order to get experience on the methodology and equipment for the testing of systems important to the safety of nuclear power plants, where the safety and reliability requirements often are very high, two different pilot systems have been tested. One system was an ABB Master application, which was loaned for testing from ABB Atom by Teollisuuden Voima Oy (TVO). Another system, loaned from Siemens AG(SAG) by IVO International Oy (IVO), was an application realized with SAG's digital SILT technology. The report describes the testing of the SAG application. The purpose of the testing was not to assess the pilot system, but to get experience in the testing methodology and find out the further development needs and potentials of the test methodology and equipment. The experience show that dynamic testing is one feasible way to get more confidence about the safety and reliability of a programmable system that would be hard to achieve by other means. It also shows that more development of the test harness is still needed, especially concerning the comparison of the obtained test response to the expected response provided by the logical model of the system. Also the user interface of the on-line part of the test harness needs development. Methods for generation of the test cases also need further development eg. for achieving statistical significance for the reliability estimates. (10 refs., 90 figs., 9 tabs.)

The sagging rope sign in achondroplasia - different from Perthes' disease

Energy Technology Data Exchange (ETDEWEB)

Shingade, Viraj U. [Korea University, Department of Paediatric Orthopaedics, College of Medicine, Guro Hospital, Seoul (Korea); Song, Hae-Ryong [Korea University, Department of Paediatric Orthopaedic Surgery, College of Medicine, Guro Hospital, Seoul (Korea); Lee, Seok-Hyun; Suh, Seung-Woo [Korea University, Department of Orthopaedic Surgery, College of Medicine, Guro Hospital, Seoul (Korea); Oh, Chang-Wug [Kyungpook National University Hospital, Department of Orthopaedic Surgery, Daegu (Korea); Hong, Jun-Seok [Ansan Hospital, Department of Orthopaedic Surgery, Korea University, Ansan, Gyeonggi do (Korea)

2006-12-15

The sagging rope sign is a radio-opaque line, seen on radiographs of the hips, with Perthes' disease. The main purpose of this study was to determine the incidence, cause and importance of this sign in achondroplasia, and to reveal how it differs from in Perthes' disease. Serial radiograms, along with 2-dimensional and 3-dimensional CT images were studied in 42 achondroplasic patients. Forty-two achondroplasic patients, reported at our institute (for routine outpatient consultation, spine surgeries, deformity corrections, limb-lengthening procedures) were included in this study. There were 26 males and 16 females. The sign was observed bilaterally, in all patients. Evaluation of CT images revealed spherical heads, with presence of circumferential overhang in all hips. This circumferential overhang, seen on 3-D CT scan, corresponded to the sagging rope sign on radiographs. Presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from Perthes' disease, and its presence does not carry a bad prognosis in achondroplasia. (orig.)

Interaction between the immune system and acute myeloid leukemia: A model incorporating promotion of regulatory T cell expansion by leukemic cells.

Science.gov (United States)

Nishiyama, Yoshiaki; Saikawa, Yutaka; Nishiyama, Nobuaki

2018-03-01

Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes. The model includes promotion of Treg expansion by leukemic blast cells, leukemic stem cell and progenitor cell targeting by Teff, and Treg-mediated Teff suppression, and exhibits two coexisting, stable steady states, corresponding to high leukemic cell load at diagnosis or relapse, and to long-term complete remission. Our model is capable of explaining the clinical findings that the survival of patients with AML after allogeneic stem cell transplantation is influenced by the duration of complete remission, and that cut-off minimal residual disease thresholds associated with a 100% relapse rate are identified in AML. Copyright © 2018 Elsevier B.V. All rights reserved.

Gravity sag view of lateral radiography of the knee

International Nuclear Information System (INIS)

Hidaka, Kuniyuki; Yanagawa, Yasuhiro; Kawamoto, Kiyosumi; Maeda, Daisuke; Komizu, Mitsuru

2007-01-01

The gravity sag view (GSV) is a lateral radiograph taken in the same position when the posterior sag sign is observed. The purpose of this study was to standardize the radiography technique for GSV by adjusting lateral rotation. To confirm the benchmark and correction angle (CA) for the GSV position, we assessed three-dimensional (3D) CT of the GSV position of the knee using normal volunteers. The benchmark is established at the 3-point of the leg and adjusting the CA of the knee is established by estimating from Rosenberg technique radiography. This helped not only to correct external rotation in the initial radiography but also to correct rotation for repeat radiography. Our method is quantitative and highly reproducible, and it increases the success rate in adjusting lateral radiography of the knee. (author)

Effect of voltage sags on digitally controlled line connected switched-mode power supplies

DEFF Research Database (Denmark)

Török, Lajos; Munk-Nielsen, Stig

2012-01-01

Different voltage disorders like voltage fluctuations, sags, frequency variations may occur in the power supply networks due to different fault conditions. These deviations from normal operation affects in different ways the line connected devices. Standards were developed to protect and ensure...... of voltage sags is analyzed. Fault tolerant control algorithm was designed, implemented and is discussed. The fault conditions and their effects were investigated at different power levels....

Facile synthesis, structure, and properties of Ag{sub 2}S/Ag heteronanostructure

Energy Technology Data Exchange (ETDEWEB)

Sadovnikov, S. I., E-mail: sadovnikov@ihim.uran.ru; Gusev, A. I. [Ural Branch of the Russian Academy of Sciences, Institute of Solid State Chemistry (Russian Federation)

2016-09-15

Ag{sub 2}S/Ag heteronanostructure has been produced by a simple one-stage chemical deposition from aqueous solutions of silver nitrate, sodium sulfide, and sodium citrate with the use of monochromatic light irradiation. For simultaneous synthesis of Ag{sub 2}S and Ag nanoparticles, deposition has been performed from reaction mixtures with reduced sodium sulfide concentration. The size of Ag{sub 2}S and Ag nanoparticles is 45–50 and 15–20 nm, respectively. It is established that in the contact layer between silver sulfide and silver, nonconducting α-Ag{sub 2}S acanthite transforms into superionic β-Ag{sub 2}S argentite under the action of external electric field. The scheme of the operation of a resistive switch based on an Ag{sub 2}S/Ag heteronanostructure is proposed. The UV–Vis optical absorption spectra of colloidal solutions of Ag{sub 2}S/Ag heteronanostructures have been studied.Graphical Abstract.

Marked in Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients after Hematopoietic Stem Cell Transplantation.

Science.gov (United States)

Wolf, Dietlinde; Barreras, Henry; Bader, Cameron S; Copsel, Sabrina; Lightbourn, Casey O; Pfeiffer, Brent J; Altman, Norman H; Podack, Eckhard R; Komanduri, Krishna V; Levy, Robert B

2017-05-01

Regulatory T cells (Tregs) are critical for self-tolerance. Although adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen, and colon (GVHD target tissue). Tregs did not expand in bone marrow, a critical site for graft-versus-malignancy responses. Adoptive transfer of in vivo-expanded Tregs in the setting of MHC-mismatched or MHC-matched allogeneic HSCT significantly ameliorated GVHD. Critically, transplantation of Treg-expanded donor cells facilitated transplant tolerance without GVHD, with complete sparing of graft-versus-malignancy. This approach may prove valuable as a therapeutic strategy promoting transplantation tolerance. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Doubly-Fed Induction Generator Control Under Voltage Sags

DEFF Research Database (Denmark)

Teodorescu, Remus; Blaabjerg, Frede; Lima, K.

2008-01-01

This paper proposes a new control technique to improve the fault-ride through capability of doubly fed induction generators (DFIG). In such generators the appearance of severe voltage sags at the coupling point make rise to high over currents at the rotor/stator windings, something that makes...

Development of assay platforms for in vitro screening of Treg modulating potential of pharmacological compounds

DEFF Research Database (Denmark)

Pedersen, Anders Elm; Holmstrøm, Kim; Jørgensen, Flemming

2015-01-01

that investigates Treg modulation by current drugs. For such research as well as for novel cell based therapies based on Treg infusions, rapid in vitro assays as well as functional assays based on inhibitory capacity of Tregs are required. Here, we report on such assays using highly pure fluorescence-activated cell...... and TNF-α. In conclusion, these assays have the potential for use in pharmacological screening and discovery in relation to drug development in immunology....

Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets

NARCIS (Netherlands)

van Herk, Egbert H.; te Velde, Anje A.

2016-01-01

T regulatory cells (Tregs) play an important role in the regulation of autoimmunity, autoinflammation, allergic diseases, infection, and the tumor environment. Different subsets are characterized that use a number of regulatory mechanisms. Tregs can influence the progression of inflammatory bowel

Mitigation of voltage sags in the distribution system with dynamic voltage restorer

International Nuclear Information System (INIS)

Viglas, D.; Belan, A.

2012-01-01

Dynamic voltage restorer is a custom power device that is used to improve voltage sags or swells in electrical distribution system. The components of the Dynamic Voltage Restorer consist of injection transformers, voltage source inverter, passive filters and energy storage. The main function of the Dynamic voltage restorer is used to inject three phase voltage in series and in synchronism with the grid voltages in order to compensate voltage disturbances. This article deals with mitigation of voltage sags caused by three-phase short circuit. Dynamic voltage restorer is modelled in MATLAB/Simulink. (Authors)

CRISPR and personalized Treg therapy: new insights into the treatment of rheumatoid arthritis.

Science.gov (United States)

Safari, Fatemeh; Farajnia, Safar; Arya, Maryam; Zarredar, Habib; Nasrolahi, Ava

2018-06-01

Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease. In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases. The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck. The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA.

Modelling voltage sag mitigation using dynamic voltage restorer and analyzing power quality issue

Science.gov (United States)

Ismail, Nor Laili; Hidzir, Hizrin Dayana Mohd; Thanakodi, Suresh; Nazar, Nazatul Shiema Moh; Ibrahim, Pungut; Ali, Che Ku Muhammad Sabri Che Ku

2018-02-01

Power quality problem which are arise due to a fault or a pulsed load can have caused an interruption of critical load. The modern power systems are becoming more sensitive to the quality of the power supplied by the utility company. Voltage sags and swells, flicker, interruptions, harmonic distortion and other distortion to the sinusoidal waveform are the examples of the power quality problems. The most affected due to these problems is industrial customers who use a lot of sensitive equipment. There has suffered a huge loss to these problems. Resulting of broken or damage equipment if voltage sag exceeds the sensitive threshold of the equipment. Thus, device such as Static Synchronous Compensator (STATCOM) and Dynamic Voltage Restorer (DVR) has been created to solve this problem among users. DVR is a custom power device that most effective and efficient. This paper intended to report the DVR operations during voltage sag compensation.

The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

Directory of Open Access Journals (Sweden)

Andrew W. Taylor

2011-01-01

Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

Advanced Control of the Dynamic Voltage Restorer for Mitigating Voltage Sags in Power Systems

Directory of Open Access Journals (Sweden)

Dung Vo Tien

2018-01-01

Full Text Available The paper presents a vector control with two cascaded loops to improve the properties of Dynamic Voltage Restorer (DVR to minimize Voltage Sags on the grid. Thereby, a vector controlled structure was built on the rotating dq-coordinate system with the combination of voltage control and the current control. The proposed DVR control method is modelled using MATLAB-Simulink. It is tested using balanced/unbalanced voltage sags as well as fluctuant and distorted voltages. As a result, by using this controlling method, the dynamic characteristics of the system have been improved significantly. The system performed with higher accuracy, faster response and lower distortion in the voltage sags compensation. The paper presents real time experimental results to verify the performance of the proposed method in real environments.

Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing.

Science.gov (United States)

Sfanos, Karen Sandell; Bruno, Tullia C; Maris, Charles H; Xu, Lauren; Thoburn, Christopher J; DeMarzo, Angelo M; Meeker, Alan K; Isaacs, William B; Drake, Charles G

2008-06-01

Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4+ and CD8+ T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer. We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was compared with naïve, peripheral blood T cells using microarray analysis. CD4+ PIL showed a paucity of TH2 (interleukin-4-secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4+ PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+) as well as towards the TH17 phenotype (interleukin-17+). We also found that a preponderance of TH17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating T(reg) revealed expected Treg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional Treg markers. Taken together, these data suggest that TH17 and/or Treg CD4+ T cells (rather than TH2 T cells) may be involved in the development or progression of prostate cancer.

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

OpenAIRE

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 huma...

Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1

OpenAIRE

Wang, Yanhua; Wang, Guangxiang; Zhang, Delin; Yin, Hong; Wang, Meng

2013-01-01

Background The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Findings Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. T...

Control Method Stretches Suspensions by Measuring the Sag of Strands in Cable-Stayed Bridges

Science.gov (United States)

Bętkowski, Piotr

2017-10-01

In the article is described the method that allows on evaluation and validation of measurement correctness of dynamometers (strain gauges, tension meters) used in systems of suspensions. Control of monitoring devices such as dynamometers is recommended in inspections of suspension bridges. Control device (dynamometer) works with an anchor, and the degree of this cooperation could have a decisive impact on the correctness of the results. Method, which determines the stress in the strand (cable), depending on the sag of stayed cable, is described. This method can be used to control the accuracy of measuring devices directly on the bridge. By measuring the strand sag, it is possible to obtain information about the strength (force) which occurred in the suspension cable. Digital camera is used for the measurement of cable sag. Control measurement should be made independently from the controlled parameter but should verify this parameter directly (it is the best situation). In many cases in practice the controlled parameter is not designation by direct measurement, but the calculations, i.e. relation measured others parameters, as in the method described in the article. In such cases occurred the problem of overlapping error of measurement of intermediate parameters (data) and the evaluation of the reliability of the results. Method of control calculations made in relation to installed in the bridge measuring devices is doubtful without procedure of uncertainty estimation. Such an assessment of the accuracy can be performed using the interval numbers. With the interval numbers are possible the analysis of parametric relationship accuracy of the designation of individual parameters and uncertainty of results. Method of measurements, relations and analytical formulas, and numerical example can be found in the text of the article.

Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1.

Science.gov (United States)

Wang, Yanhua; Wang, Guangxiang; Zhang, Delin; Yin, Hong; Wang, Meng

2013-04-30

The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. Then, shorter peptides that were derived from PS4, PS6, PS10 and PS11 were predicted using bioinformatics and tested by experimentation. Four out of nine shorter peptides were identified successfully (amino acids 106-120, 166-180, 289-300 and 313-332). We have precisely located the epitopes of T. gondii SAG1 using pig sera collected at different time points after infection. The identified epitopes may be useful for the further study of epitope-based vaccines and diagnostic reagents.

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

Science.gov (United States)

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.

Accurate antemortem diagnosis of equine protozoal myeloencephalitis (EPM) based on detecting intrathecal antibodies against Sarcocystis neurona using the SnSAG2 and SnSAG4/3 ELISAs.

Science.gov (United States)

Reed, S M; Howe, D K; Morrow, J K; Graves, A; Yeargan, M R; Johnson, A L; MacKay, R J; Furr, M; Saville, W J A; Williams, N M

2013-01-01

Recent work demonstrated the value of antigen-specific antibody indices (AI and C-value) to detect intrathecal antibody production against Sarcocystis neurona for antemortem diagnosis of equine protozoal myeloencephalitis (EPM). The study was conducted to assess whether the antigen-specific antibody indices can be reduced to a simple serum : cerebrospinal fluid (CSF) titer ratio to achieve accurate EPM diagnosis. Paired serum and CSF samples from 128 horses diagnosed by postmortem examination. The sample set included 44 EPM cases, 35 cervical-vertebral malformation (CVM) cases, 39 neurologic cases other than EPM or CVM, and 10 non-neurologic cases. Antibodies against S. neurona were measured in serum and CSF pairs using the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3) ELISAs, and the ratio of each respective serum titer to CSF titer was determined. Likelihood ratios and diagnostic sensitivity and specificity were calculated based on serum titers, CSF titers, and serum : CSF titer ratios. Excellent diagnostic sensitivity and specificity was obtained from the SnSAG2, 4/3 serum : CSF titer ratio. Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using a ratio cutoff of ≤100, whereas sensitivity and specificity were 86.4 and 95.9%, respectively, if a more rigorous cutoff of ≤50 was used. Antibody titers in CSF also provided good diagnostic accuracy. Serum antibody titers alone yielded much lower sensitivity and specificity. The study confirms the value of detecting intrathecal antibody production for antemortem diagnosis of EPM, and they further show that the antigen-specific antibody indices can be reduced in practice to a simple serum : CSF titer ratio. Copyright © 2013 by the American College of Veterinary Internal Medicine.

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

Directory of Open Access Journals (Sweden)

Hristina Nedelkovska

Full Text Available 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.

Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

Directory of Open Access Journals (Sweden)

Karina Trojan

Full Text Available There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR served as indicators for stability of Foxp3 expression. Methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations originating from peripheral blood using high resolution melt analysis. A total of 136 transplant recipients and 52 healthy controls were studied.Proportions of IFNy+ Treg were similar in patients and healthy controls (0.05% and 0.04% of all CD4+ lymphocytes; p = n.s.. Patients also had similar absolute counts of IFNy producing Helios+ and Helios- Treg (p = n.s.. Most of the IFNy+ and IFNy- Treg in transplant recipients had a methylated Foxp3 TSDR, however, there was a sizeable proportion of IFNy+ and IFNy- Treg with demethylated Foxp3 TSDR. Male and female patients showed more frequently methylated IFNy+ and IFNy- Treg than male and female controls (all p<0.05.Kidney transplant recipients with good long-term stable graft function have similar levels of IFNy+ Treg as healthy controls. IFNy+ and IFNy- Treg subsets in patients consist of cells with stable and cells with transient Foxp3 expression; however, patients showed more frequently methylated IFNy+ and IFNy- Treg than controls. The data show increased levels of Treg subsets with stable as well as transient Foxp3 expression in patients with stable allograft acceptance compared to healthy controls.

Recombinant vaccines against T. gondii: comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1.

Science.gov (United States)

Mendes, Érica Araújo; Fonseca, Flavio G; Casério, Bárbara M; Colina, Janaína P; Gazzinelli, Ricardo Tostes; Caetano, Braulia C

2013-01-01

The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1) of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector) is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination). Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1), to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.

Recombinant vaccines against T. gondii: comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1.

Directory of Open Access Journals (Sweden)

Érica Araújo Mendes

Full Text Available The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1 of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination. Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1, to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.

Energy-dependent pole expansions for the effective potentials in the four-body integral equations with tensor forces

International Nuclear Information System (INIS)

Sofianos, S.; Fiedeldey, H.; Haberzettl, H.

1980-01-01

We investigate the accuracy of the energy-dependent pole expansion for the (3+1) and (2+2) subamplitudes in the calculation of the binding energy of the α particle, E/sub α/, for separable NN potentials with tensor components. We employ the truncated t-matrix (t 00 ) approximation and compare our results for E/sub α/ to those obtained, independent of any separable expansion, by Gibson and Lehman and to the results for E/sub α/ obtained with the Hilbert-Schmidt expansion of the subamplitudes. It is shown that the energy-dependent pole expansion is both more economical and converges faster than the Hilbert-Schmidt expansion, even one term of the energy-dependent pole approximation already being accurate to better than 1.5%

The influence of motor re-acceleration on voltage sags

NARCIS (Netherlands)

Bollen, M.H.J.

1995-01-01

The assumption that a voltage sag is rectangular is not correct in a power system with large induction motor loads. The motors decelerate during the short circuit. After fault-clearing, they will accelerate again, drawing a high reactive current from the supply, causing a prolonged postfault voltage

Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

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Yan Zhou

2016-01-01

Full Text Available It is well known that dendritic cells (DCs play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs, a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG- specific experimental autoimmune encephalomyelitis (EAE model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS. Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs. Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.

Molecular analysis of Toxoplasma gondii Surface Antigen 1 (SAG1) gene cloned from Toxoplasma gondii DNA isolated from Javanese acute toxoplasmosis

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Haryati, Sri; Agung Prasetyo, Afiono; Sari, Yulia; Dharmawan, Ruben

2018-05-01

Toxoplasma gondii Surface Antigen 1 (SAG1) is often used as a diagnostic tool due to its immunodominant-specific as antigen. However, data of the Toxoplasma gondii SAG1 protein from Indonesian isolate is limited. To study the protein, genomic DNA was isolated from a Javanese acute toxoplasmosis blood samples patient. A complete coding sequence of Toxoplasma gondii SAG1 was cloned and inserted into an Escherichia coli expression plasmid and sequenced. The sequencing results were subjected to bioinformatics analysis. The Toxoplasma gondii SAG1 complete coding sequences were successfully cloned. Physicochemical analysis revealed the 336 aa of SAG1 had 34.7 kDa of weight. The isoelectric point and aliphatic index were 8.4 and 78.4, respectively. The N-terminal methionine half-life in Escherichia coli was more than 10 hours. The antigenicity, secondary structure, and identification of the HLA binding motifs also had been discussed. The results of this study would contribute information about Toxoplasma gondii SAG1 and benefits for further works willing to develop diagnostic and therapeutic strategies against the parasite.

A robust and fast generic voltage sag detection technique

DEFF Research Database (Denmark)

L. Dantas, Joacillo; Lima, Francisco Kleber A.; Branco, Carlos Gustavo C.

2015-01-01

In this paper, a fast and robust voltage sag detection algorithm, named VPS2D, is introduced. Using the DSOGI, the algorithm creates a virtual positive sequence voltage and monitories the fundamental voltage component of each phase. After calculating the aggregate value in the o:;3-reference fram...

Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients.

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Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Rao, D N

2017-03-01

The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. To study the role of IL-35 producing Tregs and Bregs in the human leprosy. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA) for 48h. Intracellular cytokine IL-35 was evaluated in CD4 + CD25 + Tregs, CD19 + cells by FACS. Expression of PD-1 on CD4 + CD25 + Tregs, CD19 + cells and its ligand (PD-L1) on B cells, CD11c cells were evaluated by flow cytometry (FACS). Serum IL-35 level was estimated by ELISA. The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosy patients (pleprosy patients. This study point out a shift in our understanding of the immunological features that mediate and regulate the immune suppression and the disease progression in leprosy patients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Continentward-dipping detachment fault system and asymmetric rift structure of the Baiyun Sag, northern South China Sea

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Zhou, Zhichao; Mei, Lianfu; Liu, Jun; Zheng, Jinyun; Chen, Liang; Hao, Shihao

2018-02-01

The rift architecture and deep crustal structure of the distal margin at the mid-northern margin of the South China Sea have been previously investigated by using deep seismic reflection profiles. However, one fundamental recurring problem in the debate is the extensional fault system and rift structure of the hyperextended rift basins (Baiyun Sag and Liwan Sag) within the distal margin because of the limited amount of seismic data. Based on new 3D seismic survey data and 2D seismic reflection profiles, we observe an array of fault blocks in the Baiyun Sag, which were tilted towards the ocean by extensional faulting. The extensional faults consistently dip towards the continent. Beneath the tilted fault blocks and extensional faults, a low-angle, high-amplitude and continuous reflection has been interpreted as the master detachment surface that controls the extension process. During rifting, the continentward-dipping normal faults evolved in a sequence from south to north, generating the asymmetric rift structure of the Baiyun Sag. The Baiyun Sag is separated from the oceanic domain by a series of structural highs that were uplifted by magmatic activity in response to the continental breakup at 33 Ma and a ridge jump to the south at 26-24 Ma. Therefore, we propose that magmatism played a significant role in the continental extension and final breakup in the South China Sea.

Pressure-dependence of the phase transitions and thermal expansion in zirconium and hafnium pyrovanadate

Energy Technology Data Exchange (ETDEWEB)

Gallington, Leighanne C.; Hester, Brett R.; Kaplan, Benjamin S. [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332‐0400 (United States); Wilkinson, Angus P., E-mail: angus.wilkinson@chemistry.gatech.edu [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332‐0400 (United States); School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332‐0245 (United States)

2017-05-15

Low or negative thermal expansion (NTE) has been previously observed in members of the ZrP{sub 2}O{sub 7} family at temperatures higher than their order-disorder phase transitions. The thermoelastic properties and phase behavior of the low temperature superstructure and high temperature negative thermal expansion phases of ZrV{sub 2}O{sub 7} and HfV{sub 2}O{sub 7} were explored via in situ variable temperature/pressure powder x-ray diffraction measurements. The phase transition temperatures of ZrV{sub 2}O{sub 7} and HfV{sub 2}O{sub 7} exhibited a very strong dependence on pressure (∼700 K GPa), with moderate compression suppressing the formation of their NTE phases below 513 K. Compression also reduced the magnitude of the coefficients of thermal expansion in both the positive and negative thermal expansion phases. Additionally, the high temperature NTE phase of ZrV{sub 2}O{sub 7} was found to be twice as stiff as the low temperature positive thermal expansion superstructure (24 and 12 GPa respectively). - Graphical abstract: The temperature at which ZrV{sub 2}O{sub 7} transforms to a phase displaying negative thermal expansion is strongly pressure dependent. The high temperature form of ZrV{sub 2}O{sub 7} is elastically stiffer than the low temperature form. - Highlights: • The order-disorder phase transition temperatures in ZrV{sub 2}O{sub 7} and HfV{sub 2}O{sub 7} are strongly pressure dependent (∼700 K.GPa). • The high temperature (disordered) phase of ZrV{sub 2}O{sub 7} is much stiffer than the ambient temperature (ordered) phase. • Compression reduces the magnitude of the negative thermal expansion in the high temperature phase of ZrV{sub 2}O{sub 7}.

Energy-dependent expansion of .177 caliber hollow-point air gun projectiles.

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Werner, Ronald; Schultz, Benno; Bockholdt, Britta; Ekkernkamp, Axel; Frank, Matthias

2017-05-01

Amongst hundreds of different projectiles for air guns available on the market, hollow-point air gun pellets are of special interest. These pellets are characterized by a tip or a hollowed-out shape in their tip which, when fired, makes the projectiles expand to an increased diameter upon entering the target medium. This results in an increase in release of energy which, in turn, has the potential to cause more serious injuries than non-hollow-point projectiles. To the best of the authors' knowledge, reliable data on the terminal ballistic features of hollow-point air gun projectiles compared to standard diabolo pellets have not yet been published in the forensic literature. The terminal ballistic performance (energy-dependent expansion and penetration) of four different types of .177 caliber hollow-point pellets discharged at kinetic energy levels from approximately 3 J up to 30 J into water, ordnance gelatin, and ordnance gelatin covered with natural chamois as a skin simulant was the subject of this investigation. Energy-dependent expansion of the tested hollow-point pellets was observed after being shot into all investigated target media. While some hollow-point pellets require a minimum kinetic energy of approximately 10 J for sufficient expansion, there are also hollow-point pellets which expand at kinetic energy levels of less than 5 J. The ratio of expansion (RE, calculated by the cross-sectional area (A) after impact divided by the cross-sectional area (A 0 ) of the undeformed pellet) of hollow-point air gun pellets reached values up of to 2.2. The extent of expansion relates to the kinetic energy of the projectile with a peak for pellet expansion at the 15 to 20 J range. To conclude, this work demonstrates that the hollow-point principle, i.e., the design-related enlargement of the projectiles' frontal area upon impact into a medium, does work in air guns as claimed by the manufacturers.

Evidence that antibodies against recombinant SnSAG1 of Sarcocystis neurona merozoites are involved in infection and immunity in equine protozoal myeloencephalitis.

Science.gov (United States)

Ellison, Siobhan; Witonsky, Sharon

2009-07-01

Sarcocystis neurona is the principal etiologic agent of equine protozoal myeloencephalitis (EPM). An immunodominant protein of S. neurona, SnSAG-1, is expressed by the majority of S. neurona merozoites isolated from spinal tissues of horses diagnosed with EPM and may be a candidate for diagnostic tests and prophylaxis for EPM. Five horses were vaccinated with adjuvanted recombinant SnSAG1 (rSnSAG1) and 5 control (sham vaccinated) horses were vaccinated with adjuvant only. Serum was evaluated pre- and post-vaccination, prior to challenge, for antibodies against rSnSAG1 and inhibitory effects on the infectivity of S. neurona by an in vitro serum neutralization assay. The effect of vaccination with rSnSAG1 on in vivo infection by S. neurona was evaluated by challenging all the horses with S. neurona merozoites. Blinded daily examinations and 4 blinded neurological examinations were used to evaluate the presence of clinical signs of EPM. The 5 vaccinated horses developed serum and cerebrospinal fluid (CSF) titers of SnSAG1, detected by enzyme-linked immunosorbent assay (ELISA), post-vaccination. Post-vaccination serum from vaccinated horses was found to have an inhibitory effect on merozoites, demonstrated by in vitro bioassay. Following the challenge, the 5 control horses displayed clinical signs of EPM, including ataxia. While 4 of the 5 vaccinated horses did not become ataxic. One rSnSAG-1 vaccinated horse showed paresis in 1 limb with muscle atrophy. All horses showed mild, transient, cranial nerve deficits; however, disease did not progress to ataxia in rSnSAG-1 vaccinated horses. The study showed that vaccination with rSnSAG-1 produced antibodies in horses that neutralized merozoites when tested by in vitro culture and significantly reduced clinical signs demonstrated by in vivo challenge.

IL-15 augments TCR-induced CD4+ T cell expansion in vitro by inhibiting the suppressive function of CD25 High CD4+ T cells.

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Tom L Van Belle

Full Text Available Due to its critical role in NK cell differentiation and CD8(+ T cell homeostasis, the importance of IL-15 is more firmly established for cytolytic effectors of the immune system than for CD4(+ T cells. The increased levels of IL-15 found in several CD4(+ T cell-driven (auto- immune diseases prompted us to examine how IL-15 influences murine CD4(+ T cell responses to low dose TCR-stimulation in vitro. We show that IL-15 exerts growth factor activity on both CD4(+ and CD8(+ T cells in a TCR-dependent and Cyclosporin A-sensitive manner. In CD4(+ T cells, IL-15 augmented initial IL-2-dependent expansion and once IL-15Rα was upregulated, IL-15 sustained the TCR-induced expression of IL-2/15Rβ, supporting proliferation independently of secreted IL-2. Moreover, IL-15 counteracts CD4(+ T cell suppression by a gradually expanding CD25(HighCD4(+ T cell subset that expresses Foxp3 and originates from CD4(+CD25(+ Tregs. These in vitro data suggest that IL-15 may dramatically strengthen the T cell response to suboptimal TCR-triggering by overcoming an activation threshold set by Treg that might create a risk for autoimmune pathology.

Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells

DEFF Research Database (Denmark)

Liu, Yawei; Marin, Andrea; Ejlerskov, Patrick

2017-01-01

Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice...... lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs. Passive transfer-EAE via IFNβ......-competent Tenc cells to mice lacking IFNβ and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes(Cre):Ifnar(fl/fl)) result in defective FoxA1(+)Tregs generation and aggravated neuroinflammation. IFNβ activates neuronal PI3K/Akt signalling and Akt binds to transcription factor FoxA1...

Energy Storage Characteristic Analysis of Voltage Sags Compensation for UPQC Based on MMC for Medium Voltage Distribution System

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Yongchun Yang

2018-04-01

Full Text Available The modular multilevel converter (MMC, as a new type of voltage source converter, is increasingly used because it is a distributed storage system. There are many advantages of using the topological structure of the MMC on a unified power quality controller (UPQC, and voltage sag mitigation is an important use of the MMC energy storage system for the power quality compensation process. In this paper, based on the analysis of the topology of the MMC, the essence of energy conversion in a UPQC of voltage sag compensation is analyzed; then, the energy storage characteristics are calculated and analyzed to determine the performance index of voltage sag compensation; in addition, the simulation method is used to verify the voltage sag compensation characteristics of the UPQC; finally, an industrial prototype of the UPQC based on an MMC for 10 kV of medium voltage distribution network has been developed, and the basic functions of UPQC have been tested.

Time-Domain Voltage Sag State Estimation Based on the Unscented Kalman Filter for Power Systems with Nonlinear Components

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Rafael Cisneros-Magaña

2018-06-01

Full Text Available This paper proposes a time-domain methodology based on the unscented Kalman filter to estimate voltage sags and their characteristics, such as magnitude and duration in power systems represented by nonlinear models. Partial and noisy measurements from the electrical network with nonlinear loads, used as data, are assumed. The characteristics of voltage sags can be calculated in a discrete form with the unscented Kalman filter to estimate all the busbar voltages; being possible to determine the rms voltage magnitude and the voltage sag starting and ending time, respectively. Voltage sag state estimation results can be used to obtain the power quality indices for monitored and unmonitored busbars in the power grid and to design adequate mitigating techniques. The proposed methodology is successfully validated against the results obtained with the time-domain system simulation for the power system with nonlinear components, being the normalized root mean square error less than 3%.

IFNy+ and IFNy- Treg subsets with stable and unstable Foxp3 expression in kidney transplant recipients with good long-term graft function.

Science.gov (United States)

Trojan, Karina; Unterrainer, Christian; Aly, Mostafa; Zhu, Li; Weimer, Rolf; Bulut, Nuray; Morath, Christian; Opelz, Gerhard; Daniel, Volker

2016-10-29

Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function. Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry. Foxp3 TSDR methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations using high resolution melt analysis. Compared with healthy controls, patients showed strong associations of IFNy secreting Helios+ and Helios- Treg with Treg that co-expressed perforin and/or CTLA4 (CD152; pterm graft function possess IFNy+ and IFNy- Treg with stable and unstable Foxp3 expression in the blood. They co-express CD28, HLADR, CTLA4, CXCR3, Lselectin, TGFβ, perforin and FasL and might contribute to the establishment and maintenance of good long-term graft function. Copyright © 2016. Published by Elsevier B.V.

Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells.

Science.gov (United States)

Ma, Hak-Ling; Napierata, Lee; Stedman, Nancy; Benoit, Stephen; Collins, Mary; Nickerson-Nutter, Cheryl; Young, Deborah A

2010-02-01

Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor alpha (TNFalpha) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNFalpha blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNFalpha blockade-induced exacerbation of skin inflammation in murine psoriasis-like skin disease. Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RB(high)CD25- (naive CD4) T cells from donor mice. These mice were treated with either anti-interleukin-12 (anti-IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNFalpha. Cytokine gene expression from these differentiated cells was also determined. Neutralization of TNFalpha exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1beta, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNFalpha also demonstrated a divergent role during priming and reactivation of naive T cells. These results reveal a novel immunoregulatory role of TNFalpha on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments.

The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation

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Shang Li

2018-01-01

Full Text Available Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs. The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

Science.gov (United States)

Sada, Yoshiharu; Dohi, Yoshihiro; Uga, Sayuri; Higashi, Akifumi; Kinoshita, Hiroki; Kihara, Yasuki

2016-08-01

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

DEPENDENT STANDARD OF HIGH EDUCATION AND THE BRAZILIAN UNIVERSITY CURRENT EXPANSION

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José Renato Bez de Gregório

2014-06-01

Full Text Available This article is based on the theoretical contributions of Florestan Fernandes seeking to analyze the structural and cyclical features of Brazilian higher education, in order to understand to what extent these features constitute the pattern-dependent learning, the historic brand dependent capitalist insertion of Brazil in the global economy and cultural heteronomy associated with it. We assume that such theoretical foundation helps us understand some aspects of the redesign of higher education underway in Brazil conducted by governments Lula da Silva and Dilma Rousseff, particularly the Program of Support to the Restructuring and Expansion of Federal Universities (REUNI. Thus, presenting some data expansion in the two largest public universities in the state of Rio de Janeiro in order to demonstrate the extent to which this process is indicating the precariousness / intensification of teaching and a deep reconfiguration of Brazilian public university.

Temperature dependence of the thermal expansion of neutron-irradiated pyrolytic carbon and graphite

International Nuclear Information System (INIS)

Matsuo, Hideto

1988-01-01

The effects of neutron irradiation and annealing on the temperature dependence of the linear thermal expansion of pyrolytic carbon and graphite were investigated after irradiation at 930-1280 0 C to a maximum neutron fluence of 2.84 x 10 25 m -2 (E > 29 fJ). After irradiation, little change in the thermal expansion of pyrolytic graphite was observed. However, as-deposited pyrolytic carbon showed an increase in thermal expansion in the perpendicular direction, a decrease in the direction parallel to the deposition plane, and also an increase in the anisotropy of the thermal expansion. Annealing at 2000 0 C did not cause any effective changes for irradiated specimens of either as-deposited pyrolytic carbon or pyrolytic graphite. (author)

Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion.

Science.gov (United States)

Coffelt, Seth B; Chen, Yung-Yi; Muthana, Munitta; Welford, Abigail F; Tal, Andrea O; Scholz, Alexander; Plate, Karl H; Reiss, Yvonne; Murdoch, Craig; De Palma, Michele; Lewis, Claire E

2011-04-01

Angiopoietin 2 (ANGPT2) is a proangiogenic cytokine whose expression is often upregulated by endothelial cells in tumors. Expression of its receptor, TIE2, defines a highly proangiogenic subpopulation of myeloid cells in circulation and tumors called TIE2-expressing monocytes/macrophages (TEMs). Genetic depletion of TEMs markedly reduces tumor angiogenesis in various tumor models, emphasizing their essential role in driving tumor progression. Previously, we demonstrated that ANGPT2 augments the expression of various proangiogenic genes, the potent immunosuppressive cytokine, IL-10, and a chemokine for regulatory T cells (Tregs), CCL17 by TEMs in vitro. We now show that TEMs also express higher levels of IL-10 than TIE2(-) macrophages in tumors and that ANGPT2-stimulated release of IL-10 by TEMs suppresses T cell proliferation, increases the ratio of CD4(+) T cells to CD8(+) T cells, and promotes the expansion of CD4(+)CD25(high)FOXP3(+) Tregs. Furthermore, syngeneic murine tumors expressing high levels of ANGPT2 contained not only high numbers of TEMs but also increased numbers of Tregs, whereas genetic depletion of tumor TEMs resulted in a marked reduction in the frequency of Tregs in tumors. Taken together, our data suggest that ANGPT2-stimulated TEMs represent a novel, potent immunosuppressive force in tumors.

Immune response to Bifidobacterium bifidum strains support Treg/Th17 plasticity.

Directory of Open Access Journals (Sweden)

Patricia López

Full Text Available In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th or regulatory (Treg responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs. Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC to further determine their capability to induce the differentiation of naïve CD4(+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed.

Analysis of doubly-fed induction machine operating at motoring mode subjected to voltage sag

Directory of Open Access Journals (Sweden)

Navneet Kumar

2016-09-01

Full Text Available Variable Speed (VS Pumped Storage Plants (PSP equipped with large asynchronous (Doubly-Fed Induction machines are emerging now in hydropower applications. Motoring mode of operation of Doubly-Fed Induction Machine (DFIM is essential and techno-economical in this application due to: (1 its uniqueness in active power controllability, (2 bulk power handing capability with less rated power converters in rotor circuit, and (3 integrating Renewable Energy Sources (RES. This paper investigates the performance of two DFIMs at different power ratings (2.2 kW and 2 MW under voltage sag with different attribute. The test results are analyzed in terms of the peaks in torque, speed, power taken and transient currents in rotor and stator circuits. During sag, stable region for DFIM operation along with speed and stator side reactive power input control is also illustrated. The negative effects of voltage sag are briefly discussed. MATLAB simulation is validated with experimentation. The various observations during simulation and experimental analysis are also supported by the theoretical explanations.

SVC or VSC for reduction of voltage sags and flicker. Trends in power electronics

Energy Technology Data Exchange (ETDEWEB)

Haeusler, M; Schnettler, A [ABB Calor Emag Schaltanlagen AG, Mannheim (Germany); Halvarsson, P [ABB Power Systems AB, Vaesteraas (Sweden)

1997-07-01

In the past complaints about insufficient power quality were often caused by flicker observed in the neighbourhood of industrial networks. Voltage sags due to faults in the power system pass, however, mostly unnoticed as not-so-common events. Now electronic controls are penetrating more and more in industry. Electronic controllers on factory machines - particularly those for variable speed motors - are vulnerable to voltage sags. A one-tenth second sag can cause a $200.000 downtime incident in a big factory. Therefore the demands on power quality are rising in industry as well. The costly separation in clean networks for residential areas and dirty networks for industrial grids is no perfect solution to avoid such problems. Static VAr Compensators (SVC) are traditionally one means to control the voltage in industrial networks. Because of the recent development of powerful gate turn-off semiconductor devices another type of converter has gained new interest for mitigation of system disturbances, the voltage-source converter (VSC). The characteristics of both types of power electronics in view of their possibilities for this application are presented. (orig.)

Simulation and experiment of a YBCO SMES prototype in voltage sag compensation

International Nuclear Information System (INIS)

Zhu Jiahui; Yuan Weijia; Coombs, T.A.; Ming, Q.

2011-01-01

Research highlights: → YBCO conductors are used in SMES. → The SMES is successfully used to compensate voltage sag by both simulation and experiment. → A new control strategy for the power converter in the SMES. - Abstract: This paper gives a introduction of a SMES unit using 2G HTS wires. A complete SMES system including both superconducting coils and control circuit has been designed to operate at 77 K. Three single-phase H-bridge converters have been used in the control circuit. A loop control signal is sent out by using 32 fixed point Digital Signal Processor (DSP). The complete circuit has been both modelled in simulation and built experimentally. The results validate that this SMES successfully compensates a voltage sag in a power system.

Simulation and experiment of a YBCO SMES prototype in voltage sag compensation

Energy Technology Data Exchange (ETDEWEB)

Zhu Jiahui, E-mail: zhujiahui@epri.sgcc.com.c [China Electric Power Research Institute, No. 15 Xiaoying Rd(E), Qinghe, Beijing 100192 (China); Yuan Weijia; Coombs, T.A. [Electrical Engineering Division, Engineering Department, University of Cambridge, CB3 0FA (United Kingdom); Ming, Q. [China Electric Power Research Institute, No. 15 Xiaoying Rd(E), Qinghe, Beijing 100192 (China)

2011-03-15

Research highlights: {yields} YBCO conductors are used in SMES. {yields} The SMES is successfully used to compensate voltage sag by both simulation and experiment. {yields} A new control strategy for the power converter in the SMES. - Abstract: This paper gives a introduction of a SMES unit using 2G HTS wires. A complete SMES system including both superconducting coils and control circuit has been designed to operate at 77 K. Three single-phase H-bridge converters have been used in the control circuit. A loop control signal is sent out by using 32 fixed point Digital Signal Processor (DSP). The complete circuit has been both modelled in simulation and built experimentally. The results validate that this SMES successfully compensates a voltage sag in a power system.

Time-of-flight expansion of binary Bose–Einstein condensates at finite temperature

Science.gov (United States)

Lee, K. L.; Jørgensen, N. B.; Wacker, L. J.; Skou, M. G.; Skalmstang, K. T.; Arlt, J. J.; Proukakis, N. P.

2018-05-01

Ultracold quantum gases provide a unique setting for studying and understanding the properties of interacting quantum systems. Here, we investigate a multi-component system of 87Rb–39K Bose–Einstein condensates (BECs) with tunable interactions both theoretically and experimentally. Such multi-component systems can be characterized by their miscibility, where miscible components lead to a mixed ground state and immiscible components form a phase-separated state. Here we perform the first full simulation of the dynamical expansion of this system including both BECs and thermal clouds, which allows for a detailed comparison with experimental results. In particular we show that striking features emerge in time-of-flight (TOF) for BECs with strong interspecies repulsion, even for systems which were separated in situ by a large gravitational sag. An analysis of the centre of mass positions of the BECs after expansion yields qualitative agreement with the homogeneous criterion for phase-separation, but reveals no clear transition point between the mixed and the separated phases. Instead one can identify a transition region, for which the presence of a gravitational sag is found to be advantageous. Moreover, we analyse the situation where only one component is condensed and show that the density distribution of the thermal component also shows some distinct features. Our work sheds new light on the analysis of multi-component systems after TOF and will guide future experiments on the detection of miscibility in these systems.

CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota homeostatic pathway.

Directory of Open Access Journals (Sweden)

Katie L Alexander

Full Text Available Cultivating an environment of mutualism between host cells and the microbiota is vital, and dysregulation of this relationship is associated with multiple immune disorders including metabolic and skin diseases, asthma, allergy, and Inflammatory Bowel Disease (IBD. One prominent mechanism for maintaining homeostasis is the protective regulatory T cell (Treg- Immunoglobulin A (IgA pathway toward microbiota antigens, in which Tregs maintain homeostasis and provide critical survival factors to IgA+ B cells. In order to amplify the Treg-IgA pathway, we have generated a fusion protein, CBirTox, comprised of a portion of the carboxy terminus of CBir1, a microbiota flagellin, genetically coupled to Cholera Toxin B subunit (CTB via the A2 linker of CT. Both dendritic cells (DCs and B cells pulsed with CBirTox selectively induced functional CD4+Foxp3+ Tregs in vitro, and CBirTox augmented CD4+Foxp3+ cell numbers in vivo. The induced Foxp3 expression was independent of retinoic acid (RA signaling but was inhibited by neutralization of TGF-β. CBirTox treatment of B cells downregulated mammalian target of rapamycin (mTOR signaling. Furthermore, CBirTox-pulsed DCs induced substantial production of IgA from naïve B cells. Collectively these data demonstrate that CBirTox represents a novel approach to bolstering the Treg-IgA pathway at the host-microbiota interface.

Optimal Cable Tension Distribution of the High-Speed Redundant Driven Camera Robots Considering Cable Sag and Inertia Effects

Directory of Open Access Journals (Sweden)

Yu Su

2014-03-01

Full Text Available Camera robots are high-speed redundantly cable-driven parallel manipulators that realize the aerial panoramic photographing. When long-span cables and high maneuverability are involved, the effects of cable sags and inertias on the dynamics must be carefully dealt with. This paper is devoted to the optimal cable tension distribution (OCTD for short of the camera robots. Firstly, each fast varying-length cable is discretized into some nodes for computing the cable inertias. Secondly, the dynamic equation integrated with the cable inertias is set up regarding the large-span cables as catenaries. Thirdly, an iterative optimization algorithm is introduced for the cable tension distribution by using the dynamic equation and sag-to-span ratios as constraint conditions. Finally, numerical examples are presented to demonstrate the effects of cable sags and inertias on determining tensions. The results justify the convergence and effectiveness of the algorithm. In addition, the results show that it is necessary to take the cable sags and inertias into consideration for the large-span manipulators.

Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani.

Directory of Open Access Journals (Sweden)

Sanchita Das

Full Text Available Sodium antimony gluconate (SAG unresponsiveness of Leishmania donovani (Ld had effectively compromised the chemotherapeutic potential of SAG. 60s ribosomal L23a (60sRL23a, identified as one of the over-expressed protein in different resistant strains of L.donovani as observed with differential proteomics studies indicates towards its possible involvement in SAG resistance in L.donovani. In the present study 60sRL23a has been characterized for its probable association with SAG resistance mechanism.The expression profile of 60s ribosomal L23a (60sRL23a was checked in different SAG resistant as well as sensitive strains of L.donovani clinical isolates by real-time PCR and western blotting and was found to be up-regulated in resistant strains. Ld60sRL23a was cloned, expressed in E.coli system and purified for raising antibody in swiss mice and was observed to have cytosolic localization in L.donovani. 60sRL23a was further over-expressed in sensitive strain of L.donovani to check its sensitivity profile against SAG (Sb V and III and was found to be altered towards the resistant mode.This study reports for the first time that the over expression of 60sRL23a in SAG sensitive parasite decreases the sensitivity of the parasite towards SAG, miltefosine and paramomycin. Growth curve of the tranfectants further indicated the proliferative potential of 60sRL23a assisting the parasite survival and reaffirming the extra ribosomal role of 60sRL23a. The study thus indicates towards the role of the protein in lowering and redistributing the drug pressure by increased proliferation of parasites and warrants further longitudinal study to understand the underlying mechanism.

Optimum distributed generation placement with voltage sag effect minimization

International Nuclear Information System (INIS)

Biswas, Soma; Goswami, Swapan Kumar; Chatterjee, Amitava

2012-01-01

Highlights: ► A new optimal distributed generation placement algorithm is proposed. ► Optimal number, sizes and locations of the DGs are determined. ► Technical factors like loss, voltage sag problem are minimized. ► The percentage savings are optimized. - Abstract: The present paper proposes a new formulation for the optimum distributed generator (DG) placement problem which considers a hybrid combination of technical factors, like minimization of the line loss, reduction in the voltage sag problem, etc., and economical factors, like installation and maintenance cost of the DGs. The new formulation proposed is inspired by the idea that the optimum placement of the DGs can help in reducing and mitigating voltage dips in low voltage distribution networks. The problem is configured as a multi-objective, constrained optimization problem, where the optimal number of DGs, along with their sizes and bus locations, are simultaneously obtained. This problem has been solved using genetic algorithm, a traditionally popular stochastic optimization algorithm. A few benchmark systems radial and networked (like 34-bus radial distribution system, 30 bus loop distribution system and IEEE 14 bus system) are considered as the case study where the effectiveness of the proposed algorithm is aptly demonstrated.

Application of Boost Converter for Ride-through Capability of Adjustable Speed Drives during Sag and Swell Conditions

OpenAIRE

S. S. Deswal; Ratna Dahiya; D. K. Jain

2008-01-01

Process control and energy conservation are the two primary reasons for using an adjustable speed drive. However, voltage sags are the most important power quality problems facing many commercial and industrial customers. The development of boost converters has raised much excitement and speculation throughout the electric industry. Now utilities are looking to these devices for performance improvement and reliability in a variety of areas. Examples of these include sags,...

Cyclic AMP-Responsive Element-Binding Protein (CREB is Critical in Autoimmunity by Promoting Th17 but Inhibiting Treg Cell Differentiation

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Xiaohu Wang

2017-11-01

Full Text Available The molecular mechanisms that govern differential T cell development into pro-inflammatory Th17 vs. regulatory T (Treg cells remain unclear. Here, we show that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell differentiation in vitro and in vivo, and led to resistance to autoimmune diseases. Mechanistically, CREB, activated by CD3-PKC-ϴ signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable for FOXP3 expression and for the homeostasis and suppressive function of thymus-derived Treg cells, CREB negatively regulates the survival of TGF-β-induced Treg cells, and deletion of CREB resulted in increased FOXP3+ Treg cells in the intestine and protection in a colitis model. Thus, CREB is critical in autoimmune diseases by promoting Th17 cell and inhibiting de novo Treg cell generation.

Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

KAUST Repository

Schmidt, Angelika; Marabita, Francesco; Kiani, Narsis A.; Gross, Catharina C.; Johansson, Henrik J.; É liá s, Szabolcs; Rautio, Sini; Eriksson, Matilda; Fernandes, Sunjay Jude; Silberberg, Gilad; Ullah, Ubaid; Bhatia, Urvashi; Lä hdesmä ki, Harri; Lehtiö , Janne; Gomez-Cabrero, David; Wiendl, Heinz; Lahesmaa, Riitta; Tegner, Jesper

2018-01-01

BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest

Deriving Sight Distance on a Compound Sag and Circular Curve in a Three Dimensional Space

Directory of Open Access Journals (Sweden)

Chiu Liu, PhD, PE, PTOE

2012-09-01

Full Text Available Insufficient roadway sight distance (SD may become a contribution factor to traffic collisions or other unsafe traffic maneuvers. The sight distance (SD for a two-dimensional (2-d sag or circular curve has been addressed in detail in various traffic engineering literatures. Although three-dimensional (3-d compound sag and circular curves are often found along ramps, connectors, and mountain roads, the sight distances for these compound curves are yet to be analyzed on an exact analytic setting. By considering human-vehicle-roadway interaction, the formulas for computing the SD on a 3-d curve are derived the first time on a unified analytic framework. The 2-d sag curve SD can also be deduced from these derived formulas as special limiting cases. Practitioners can easily program these formulas or equations on a user-friendly Microsoft Excel spread sheet to calculate 3-d SD on most roadways with roadside clearance. This framework can be extended to estimate SD on roadways with obstacles partially blocking vehicle headlight beams. 6.

Generation Expansion Planning With Large Amounts of Wind Power via Decision-Dependent Stochastic Programming

Energy Technology Data Exchange (ETDEWEB)

Zhan, Yiduo; Zheng, Qipeng P.; Wang, Jianhui; Pinson, Pierre

2017-07-01

Power generation expansion planning needs to deal with future uncertainties carefully, given that the invested generation assets will be in operation for a long time. Many stochastic programming models have been proposed to tackle this challenge. However, most previous works assume predetermined future uncertainties (i.e., fixed random outcomes with given probabilities). In several recent studies of generation assets' planning (e.g., thermal versus renewable), new findings show that the investment decisions could affect the future uncertainties as well. To this end, this paper proposes a multistage decision-dependent stochastic optimization model for long-term large-scale generation expansion planning, where large amounts of wind power are involved. In the decision-dependent model, the future uncertainties are not only affecting but also affected by the current decisions. In particular, the probability distribution function is determined by not only input parameters but also decision variables. To deal with the nonlinear constraints in our model, a quasi-exact solution approach is then introduced to reformulate the multistage stochastic investment model to a mixed-integer linear programming model. The wind penetration, investment decisions, and the optimality of the decision-dependent model are evaluated in a series of multistage case studies. The results show that the proposed decision-dependent model provides effective optimization solutions for long-term generation expansion planning.

Aberrant Muscle Antigen Exposure in Mice Is Sufficient to Cause Myositis in a Treg Cell–Deficient Milieu

Science.gov (United States)

Young, Nicholas A; Sharma, Rahul; Friedman, Alexandra K; Kaffenberger, Benjamin H; Bolon, Brad; Jarjour, Wael N

2013-01-01

Objective Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell–deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. Methods FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)–null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1–null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. Results FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. Conclusion These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity. PMID:24022275

Down-regulation of OsSAG12-1 results in enhanced senescence ...

Indian Academy of Sciences (India)

2013-07-22

Jul 22, 2013 ... vides staple food nearly half of the world's population and accounts .... Healthy and fresh onion ... served domain comprising approximate 210 aa belongs to the peptidase ..... Lim PO, Kim HJ and Nam HG 2007 Leaf senescence. Annu. Rev. ... Effects of P(SAG12)-IPT gene expression on development and.

SAG2 locus genotyping of Toxoplasma gondii in meat products of ...

African Journals Online (AJOL)

Jane

2011-10-12

Oct 12, 2011 ... restriction fragment length polymorphism (RFLP) analysis of SAG2 locus revealed that all of the samples belonged to genotype I. The detection of the parasite in uncooked meat and commercial meat products, and the high ratio of seropositive slaughtered animals, emphasis that the risk still exists for.

SAG/ROC-SCFβ-TrCP E3 Ubiquitin Ligase Promotes Pro-Caspase-3 Degradation as a Mechanism of Apoptosis Protection

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Mingjia Tan

2006-12-01

Full Text Available Skp1-cullin-F-box protein (SCF is a multicomponent E3 ubiquitin (Ub ligase that ubiquitinates a number of important biologic molecules such as p27, β-catenin, and lκB for proteasomal degradation, thus regulating cell proliferation and survival. One SCF component, SAG/ROC2/Rbx2/Hrt2, a RING finger protein, was first identified as a redox-inducible protein, which, when overexpressed, inhibited apoptosis both in vitro and in vivo. We report here that sensitive to apoptosis gene (SAG, as well as its family member ROC1/Rbxi, bound to the proinactive form of caspase-3 (pro-caspase-3. Binding was likely mediated through F-box protein, β-transducin repeat-containing protein (β-TrCP, which binds to the first 38 amino acids of pro-caspase-3. Importantly, β-TrCP1 expression significantly shortened the protein half-life of pro-caspase-3, whereas expression of a dominant-negative β-TrCP1 mutant with the F-box domain deleted extended it. An in vitro ubiquitination assay showed that SAG/ROC-SCF -Trcp promoted ubiquitination of pro-caspase-3. Furthermore, endogenous levels of pro-caspase-3 were decreased by overexpression of SAG/ROC-SCFβ-TrCP E3 Ub ligases, but increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1, or β-TrCPs, leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing ligand through increased activation of caspase-3. Thus, pro-caspase-3 appears to be a substrate of SAG/ROC-SCFβ-TrCP E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3.

Thermal expansion and cooling rate dependence of transition temperature in ZrTiO4 single crystal

International Nuclear Information System (INIS)

Park, Y.

1998-01-01

Thermal expansion in ZrTiO 4 single crystal was investigated in the temperature range covering the normal, incommensurate, and commensurate phases. Remarkable change was found at the normal-incommensurate phase transition (T I ) in all thermal expansion coefficients a, b, and c. The spontaneous strains χ as and χ bs along the a and b axes show linear temperature dependence, while the spontaneous strain χ cs along the c axis shows a nonlinear temperature dependence. Small discontinuity along the c direction was observed at the incommensurate-commensurate transition temperature, T c = 845 C. dT I /dP and dT c /dP depend on the cooling rate

La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino

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Gabriel Cabrera

2011-06-01

Full Text Available El virus del tumor mamario murino (MMTV es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg CD4+CD25+Foxp3+ específicas para el superantígeno (Sag viral en las placas de Peyer (PP. En este trabajo se evaluó si la depleción de las células Treg influencia la población de células CD8+ durante la infección con MMTV a través del amamantamiento. La depleción de las células Treg al día 6 de infección causó incrementos en el porcentaje y número absoluto de las células CD8+ en los ganglios y provocó un incremento en la intensidad de fluorescencia media del marcador de activación CD44 en esas células. Los incrementos en el número absoluto de las células CD8 se observaron en células con cadenas variables Vβ del receptor de las células T (TCR tanto reactivas como no reactivas al Sag. Previamente habíamos demostrado que la depleción de las células Treg al día 6 de infección disminuye la carga viral. Los resultados presentados en este trabajo sugieren que, al menos a partir del día 6 de infección con MMTV, las células Treg podrían tener un rol inhibiendo la generación de una respuesta CD8 antiviral.

SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apoptosis in RA

NARCIS (Netherlands)

van der Geest, Kornelis S. M.; Smigielska, Katarzyna; Park, Ji-Ah; Abdulahad, Wayel H.; Kim, Hye-Won; Kroesen, Bart-Jan; van den Berg, Anke; Boots, Annemieke M. H.; Lee, Eun-Bong; Brouwer, Elisabeth

Objective. The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients. Methods. Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker

Interest of retro-anal levator plate myorrhaphy in selected cases of descending perineum syndrome with positive anti-sagging test

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Beco Jacques

2008-07-01

Full Text Available Abstract Background Levator plate sagging (LPS, usually called descending perineum syndrome, is one of the main defects encountered in perineology. This defect is classically associated with colo-proctologic functional troubles (dyschesia and anal incontinence but can also induce perineodynia, gynaecological and lower urinary tract symptoms. Methods A retrospective case series of nine female patients (mean age: 44.3 underwent an isolated retro-anal levator plate myorrhaphy (RLPM to treat symptomatic LPS confirmed by rectal examination and/or Perineocaliper®. An anti-sagging test (support of the posterior perineum must significantly improve the symptoms that were resistant to conservative treatment. The effect of the procedure on the symptoms of the 3 axes of the perineum (urological, colo-proctologic and gynecological and on perineodynia was evaluated during a follow up consultation more than 9 months after surgery. The effect of RLPM on the position of the anal margin and on the levator plate angle was studied using rectal examination, Perineocaliper® and retro-anal ultrasound. Results Before surgery, anti-sagging tests were positive for dyschesia, urinary urgency and pain. After a mean follow-up of 16.1 months, RLPM resolved or improved 2/2 cases of stress urinary incontinence, 3/5 of urinary urgency, 3/4 of dysuria, 3/3 of anal incontinence, 7/8 of dyschesia, 3/4 of cystocele, 4/5 of rectocele, 5/8 of dyspareunia and 6/7 of perineodynia. Rectal examination showed a complete suppression of sagging in 4 patients and an improvement in the 5 others. The mean reduction of perineal descent was 1.08 cm (extremes: 0–1.5. Using retro-anal ultrasound of the levator plate, the mean reduction of sagging was 12.67 degrees (extremes: 1 – 21. Conclusion Anti-sagging tests can be used before surgery to simulate the effect of RLPM. This surgical procedure seems to improve stress urinary incontinence, frequency, nocturia, urgency, dysuria, anal

La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino

OpenAIRE

Gabriel Cabrera; Juliana Mundiñano; Gabriela Camicia; Héctor Costa; Irene Nepomnaschy; Isabel Piazzon

2011-01-01

El virus del tumor mamario murino (MMTV) es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg) CD4+CD25+Foxp3+ específicas para el superantígeno (Sag) viral en las placas de Peyer (PP). En este trabajo se evaluó si la depleción de las células Treg influen...

Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection

Directory of Open Access Journals (Sweden)

Xue-Song Liang

2012-05-01

Full Text Available Abstract Background Many studies suggest that in chronic hepatitis B virus (HBV infection regulate T (Treg cells and interlukin-17-producing T help cells (Th17 are mutually antagonistic in the immune response. This study is aimed to reveal the cell differentiation environment and the significance of Treg and Th17 balance in the development of acute and chronic HBV infection. Methods Ten patients with acute HBV infection (AHB and forty-eight patients with chronic HBV infection, including 12 asymptomatic HBV carriers (HBV carriers, 18 chronic hepatitis B patients (CHB and 18 acute-on-chronic HBV-related liver failure (ACHBLF were enrolled. Treg and Th17 cells differentiation related cytokine levels were detected by using ELISA. Flow cytometry was employed to count the Treg and Th17 frequency in peripheral blood. Results Compared to health controls both AHB and ACHBLF patients favoured Th17 cell differentiation, accompanied by a higher proportion of peripheral Th17 cells (P  Conclusions Th17 cells are involved in acute and chronic HBV infection, especially in AHB and ACHBLF. CHB and ACHBLF patients manifested obvious Treg/Th17 ratio imbalance, which might be linked to disease progression and the continuous HBV infection.

Voltage Sag Mitigation and Load Reactive Power Compensation by UPQC

OpenAIRE

Ajitha, P; Jananisri, D

2014-01-01

This paper presents Unified Power Quality Conditioner(UPQC) that consist of series inverter and shunt inverter in back to back configuration which simultaneously compensate the power quality(PQ) problems of both voltage sag and load reactive power compensation . In this paper ,Neural network is tool which is considered for solving power quality problems. The simulation results from MATLAB/SIMULINK are discussed to validate the proposed method.

Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

OpenAIRE

LI Dong; LU Zhonghua; GAN Jianhe

2016-01-01

ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin ［lipopolysaccharide (LPS)］/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and ...

The rice OsSAG12-2 gene codes for a functional protease that ...

Indian Academy of Sciences (India)

2016-07-11

Jul 11, 2016 ... Senescence is the final stage of plant development. Although ... Down-regulation of OsSAG12-1 in transgenic rice .... Plants were germinated on soil and grown for 15 days under normal conditions before taking photograph.

Evolution of depositional system and uraniferous characteristics of Damoguaihe formation in Kelulun sag

International Nuclear Information System (INIS)

Zhang Zhijie; Yu Xinghe; Zhang Chuanheng; Chen Zhankun

2005-01-01

Damoguaihe Formation, which is mainly of alluvial fan, fan delta and lacustrine depositional systems, is the target horizon for the prospecting of sandstone-type uranium deposit in Kelulun sag, Hailaer basin. According to the depositional environment and sediment characteristics, alluvial fan facies is subdivided into upper fan, middle fan and lower fan subfacies; the fan delta facies is subadivided into upper fan delta plain, lower fan delta plain, fan delta front and fan prodelta subfacies. At the northern edge of the sag occurred one fan delta and one alluvial fan, which can mutually transform one into another. The terrigenous coarse-grained clastic deposits in the study area provide favorable condition for the concentration of uranium and especially the main channels and distributary channels on the fan delta and alluvial fan are the most favorable sites for uranium concentration. (authors)

[Th17 and Treg cell levels in patients with sarcoidosis and their relation to disease activation].

Science.gov (United States)

Weng, Yue-song; Wang, Hua-ying; Lv, Ding-feng; Fu, Zhong-ming; Yu, Wan-jun

2015-03-01

To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment. Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated. Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all PSACE (r= 0.781). The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis, which was associated with the activity of disease, and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance.

Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID.

Science.gov (United States)

Sauer, Aisha V; Brigida, Immacolata; Carriglio, Nicola; Hernandez, Raisa Jofra; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna; Aiuti, Alessandro

2012-02-09

Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)-mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA-treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA(-/-) Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA-treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA-treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID.

Depletion of Treg cells augments the therapeutic effect of cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2006-01-01

Roč. 52, č. 6 (2006), s. 202-204 ISSN 0015-5500 Grant - others:EU-FP6-Clinigene(XE) 018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : Treg cells * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.387, year: 2006

Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

Science.gov (United States)

Yin, Yuan; Cai, Xing; Chen, Xi; Liang, Hongwei; Zhang, Yujing; Li, Jing; Wang, Zuoyun; Chen, Xiulan; Zhang, Wen; Yokoyama, Seiji; Wang, Cheng; Li, Liang; Li, Limin; Hou, Dongxia; Dong, Lei; Xu, Tao; Hiroi, Takachika; Yang, Fuquan; Ji, Hongbin; Zhang, Junfeng; Zen, Ke; Zhang, Chen-Yu

2014-01-01

An increased population of CD4+CD25highFoxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles (MVs). In targeted mouse peripheral CD4+ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog (PTEN) and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides (ASOs) into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion. PMID:25223704

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

Science.gov (United States)

Li, Xia; Wang, Bin; Li, Yuzhu; Wang, Li; Zhao, Xiangzhong; Zhou, Xianbin; Guo, Yuqi; Jiang, Guosheng; Yao, Chengfang

2013-01-09

The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17

Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID

Science.gov (United States)

Sauer, Aisha V.; Brigida, Immacolata; Carriglio, Nicola; Jofra Hernandez, Raisa; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L.; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna

2012-01-01

Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)–mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA–treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA−/− Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA–treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA–treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. Trials were registered at www.clinicaltrials.gov as NCT00598481/NCT00599781. PMID:22184407

Influence of budesonide and salbutamol atomization inhalation on Th17/ Treg balance in patients with bronchial asthma and its correlation with airway remodeling

Directory of Open Access Journals (Sweden)

Kun-Feng Zhang1

2017-05-01

Full Text Available Objective: To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling. Methods: A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45 and observation group (n=45 according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results: Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF-αcontents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes. Conclusion: Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.

An edgeworth expansion for a sum of M-Dependent random variables

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Wan Soo Rhee

1985-01-01

Full Text Available Given a sequence X1,X2,…,Xn of m-dependent random variables with moments of order 3+α (0<α≦1, we give an Edgeworth expansion of the distribution of Sσ−1(S=X1+X2+…+Xn, σ2=ES2 under the assumption that E[exp(it Sσ1] is small away from the origin. The result is of the best possible order.

Modified Fourth-Order Kinetic Energy Gradient Expansion with Hartree Potential-Dependent Coefficients.

Science.gov (United States)

Constantin, Lucian A; Fabiano, Eduardo; Della Sala, Fabio

2017-09-12

Using the semiclassical neutral atom theory, we developed a modified fourth-order kinetic energy (KE) gradient expansion (GE4m) that keeps unchanged all the linear-response terms of the uniform electron gas and gives a significant improvement with respect to the known semilocal functionals for both large atoms and jellium surfaces. On the other hand, GE4m is not accurate for light atoms; thus, we modified the GE4m coefficients making them dependent on a novel ingredient, the reduced Hartree potential, recently introduced in the Journal of Chemical Physics 2016, 145, 084110, in the context of exchange functionals. The resulting KE gradient expansion functional, named uGE4m, belongs to the novel class of u-meta-generalized-gradient-approximations (uMGGA) whose members depend on the conventional ingredients (i.e., the reduced gradient and Laplacian of the density) as well as on the reduced Hartree potential. To test uGE4m, we defined an appropriate benchmark (including total KE and KE differences for atoms, molecules and jellium clusters) for gradient expansion functionals, that is, including only those systems which are mainly described by a slowly varying density regime. While most of the GGA and meta-GGA KE functionals (we tested 18 of them) are accurate for some properties and inaccurate for others, uGE4m shows a consistently good performance for all the properties considered. This represents a qualitative boost in the KE functional development and highlights the importance of the reduced Hartree potential for the construction of next-generation KE functionals.

The relationship between the Johnson-Baranger time-dependent folded diagram expansion and the time-independent methods of perturbation theory

International Nuclear Information System (INIS)

Passos, E.M.J. de

1976-01-01

The relationship between the Johnson-Baranger time-dependent folded diagram (JBFD) expansion, and the time independent methods of perturbation theory, are investigated. In the nondegenerate case, the JBFD expansion and the Rayleigh-Schroedinger perturbation expansion, for the ground state energy, are identical. On the other hand, in the degenerate case, for the nonhermitian effective interaction considered, the JBFD expansion, of the effective interaction, is equal to the perturbative expansion of the effective interaction of the nonhermitian eigenvalue problem of Bloch and Brandow-Des Cloizeaux. For the two hermitian effective interactions, the JBFD expansion of the effective interaction differs from the perturbation expansion of the effective interaction of the hermitian eigenvalue problem of Des Cloizeaux [pt

Control of hybrid fuel cell/energy storage distributed generation system against voltage sag

Energy Technology Data Exchange (ETDEWEB)

Hajizadeh, Amin; Golkar, Masoud Aliakbar [Electrical Engineering Department, K.N. Toosi University of Technology, Seyedkhandan, Dr. Shariati Ave, P.O. Box 16315-1355, Tehran (Iran)

2010-06-15

Fuel cell (FC) and energy storage (ES) based hybrid distributed power generation systems appear to be very promising for satisfying high energy and high power requirements of power quality problems in distributed generation (DG) systems. In this study, design of control strategy for hybrid fuel cell/energy storage distributed power generation system during voltage sag has been presented. The proposed control strategy allows hybrid distributed generation system works properly when a voltage disturbance occurs in distribution system and hybrid system stays connected to the main grid. Hence, modeling, controller design, and simulation study of a hybrid distributed generation system are investigated. The physical model of the fuel cell stack, energy storage and the models of power conditioning units are described. Then the control design methodology for each component of the hybrid system is proposed. Simulation results are given to show the overall system performance including active power control and voltage sag ride-through capability of the hybrid distributed generation system. (author)

Analysis the Transient Process of Wind Power Resources when there are Voltage Sags in Distribution Grid

Science.gov (United States)

Nhu Y, Do

2018-03-01

Vietnam has many advantages of wind power resources. Time by time there are more and more capacity as well as number of wind power project in Vietnam. Corresponding to the increase of wind power emitted into national grid, It is necessary to research and analyze in order to ensure the safety and reliability of win power connection. In national distribution grid, voltage sag occurs regularly, it can strongly influence on the operation of wind power. The most serious consequence is the disconnection. The paper presents the analysis of distribution grid's transient process when voltage is sagged. Base on the analysis, the solutions will be recommended to improve the reliability and effective operation of wind power resources.

Microbiota-specific CD4CD8αα Tregs: role in intestinal immune homeostasis and implications for IBD

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Guillaume eSARRABAYROUSE

2015-10-01

Full Text Available 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 irritable 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.

Inrush Transient Current Analysis and Suppression of Photovoltaic Grid-Connected Inverters During Voltage Sag

DEFF Research Database (Denmark)

Li, Zhongyu; Zhao, Rende; Xin, Zhen

2016-01-01

The Inrush Transient Current (ITC) in the output of the photovoltaic grid-connected inverters is usually generated when grid voltage sag occurs, which can trigger the protection of the grid-connected inverters, and even destroy the semiconductor switches. Then, the grid-connected inverters...

Biological Mechanisms Underlying the Ultraviolet Radiation-Induced Formation of Skin Wrinkling and Sagging I: Reduced Skin Elasticity, Highly Associated with Enhanced Dermal Elastase Activity, Triggers Wrinkling and Sagging

Science.gov (United States)

Imokawa, Genji; Ishida, Koichi

2015-01-01

The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic fibers together with decreased skin elasticity, whose magnitudes are greater in UVB-exposed skin than in UVA-exposed skin. Comparison of skin elasticity with the activity of matrix metalloproteinases (MMPs) in the dermis of ovariectomized rats after UVB or UVA irradiation demonstrates that skin elasticity is more significantly decreased in ovariectomized rats than in sham-operated rats, which is accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV. Clinical studies using animal skin and human facial skin demonstrated that topical treatment with a specific inhibitor or an inhibitory extract of skin fibroblast-derived elastase distinctly attenuates UVB and sunlight-induced formation of wrinkling. Our results strongly indicated that the upregulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. PMID:25856675

Mitigation of Unbalanced Voltage Sags and Voltage Unbalance in CIGRE Low Voltage Distribution Network

DEFF Research Database (Denmark)

Mustafa, Ghullam; Bak-Jensen, Birgitte; Mahat, Pukar

2013-01-01

Any problem with voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM) etc. can be used to mitigate the voltage problems in the distribution system...... to unbalanced faults. The compensation of unbalanced voltage sags and voltage unbalance in the CIGRE distribution network is done by using the four STATCOM compensators already existing in the test grid. The simulations are carried out in DIgSILENT power factory software version 15.0........ The voltage problems dealt with in this paper are to show how to mitigate unbalanced voltage sags and voltage unbalance in the CIGRE Low Voltage (LV) test network and net-works like this. The voltage unbalances, for the tested cases in the CIGRE LV test network are mainly due to single phase loads and due...

Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

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Joonhee Cho

Full Text Available Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI.To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function.BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6.17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a therapeutic approach to DILI.

Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

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Katherine J Kasper

2014-05-01

Full Text Available Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS, how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6 mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

Science.gov (United States)

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention

Role of Fas and Treg cells in fracture healing as characterized in the fas-deficient (lpr) mouse model of lupus.

Science.gov (United States)

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-06-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Fas(lpr) /J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Fas(lpr) /J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Fas(lpr) /J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Fas(lpr) /J mice had elevated Treg cells in both spleens and bones of B6.MRL/Fas(lpr) /J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Fas(lpr) /J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Fas(lpr) /J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings

Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells.

Science.gov (United States)

Essig, Katharina; Hu, Desheng; Guimaraes, Joao C; Alterauge, Dominik; Edelmann, Stephanie; Raj, Timsse; Kranich, Jan; Behrens, Gesine; Heiseke, Alexander; Floess, Stefan; Klein, Juliane; Maiser, Andreas; Marschall, Susan; Hrabĕ de Angelis, Martin; Leonhardt, Heinrich; Calkhoven, Cornelis F; Noessner, Elfriede; Brocker, Thomas; Huehn, Jochen; Krug, Anne B; Zavolan, Mihaela; Baumjohann, Dirk; Heissmeyer, Vigo

2017-12-19

Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhanced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner

Science.gov (United States)

McDonald-Hyman, Cameron; Flynn, Ryan; Panoskaltsis-Mortari, Angela; Peterson, Nicholas; MacDonald, Kelli P. A.; Hill, Geoffrey R.; Luznik, Leo; Serody, Jonathan S.; Murphy, William J.; Maillard, Ivan; Munn, David H.; Turka, Laurence A.; Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL-2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL-2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID:27385791

Measurement of Linear Coefficient of Thermal Expansion and Temperature-Dependent Refractive Index Using Interferometric System

Science.gov (United States)

Corsetti, James A.; Green, William E.; Ellis, Jonathan D.; Schmidt, Greg R.; Moore, Duncan T.

2017-01-01

A system combining an interferometer with an environmental chamber for measuring both coefficient of thermal expansion (CTE) and temperature-dependent refractive index (dn/dT) simultaneously is presented. The operation and measurement results of this instrument are discussed.

Regulating the Balance of Th17/Treg via Electroacupuncture and Moxibustion: An Ulcerative Colitis Mice Model Based Study

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Jungang Sun

2017-01-01

Full Text Available Aim. To investigate the relationship between the effects of electroacupuncture/moxibustion and the balance of Th17/Treg in treating ulcerative colitis (UC and to preliminary compare the effects of the above two methods. Methods. DSS-induced UC mice were treated by electroacupuncture and moxibustion. Disease activity index (DAI was scored; intestinal pathological structure and ultrastructure were observed. The levels of IL-2, IL-6, IL-10, IL-17A, IL-17F, and TGF-β in plasma were measured by ELISA. The percentages of Treg and Th17 in spleen lymphocytes were analyzed by flow cytometry. Also, the expressions of TLR2, TLR4, RORγt, and FOXP3 in the distal colon were detected by immunohistochemistry or western blot. Results. Both electroacupuncture and moxibustion can relieve UC. These effects are further supported by ELISA results. In addition, the ratio of Treg and Th17 in spleen lymphocytes and the expression of TLR2 and TLR4 are significantly improved. Also, the expression of RORγt and FOXP3 in distal colon were improved. Besides, the effect of moxibustion is better than that of electroacupuncture on TLR2, TLR4, and FOXP3 expression (P<0.05. Conclusion. Both electroacupuncture and moxibustion may ameliorate UC by regulating the balance of Th17/Treg. Whether moxibustion has better efficacy than electroacupuncture needs further study.

Delayed expression of SAGs correlates with longevity in CMS wheat plants compared to its fertile plants.

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Semwal, Vimal Kumar; Singh, Bhupinder; Khanna-Chopra, Renu

2014-04-01

Reproductive sinks regulate monocarpic senescence in crop plants. Monocarpic senescence was studied in wheat fertile (cv. HW 2041) and its isonuclear cytoplasmic male sterile (CMS) line. CMS plants exhibited slower rate of senescence accompanied by longer green leaf area duration and slower deceleration in chlorophyll, protein content, PN and rubisco content coupled with lower protease activities than fertile (F) plants. CMS plants also exhibited lower ROS levels and less membrane damage than F plants. CMS plants maintained better antioxidant defense, less oxidative damage in chloroplast and higher transcript levels of both rbcL and rbcS genes during senescence than F plants. F plants exhibited early induction and higher expression of SAGs like serine and cysteine proteases, glutamine synthetases GS1 and GS2, WRKY53 transcription factor and decline in transcript levels of CAT1 and CAT2 genes than CMS plants. Hence, using genetically fertile and its CMS line of wheat it is confirmed that delayed senescence in the absence of reproductive sinks is linked with slower protein oxidation, rubisco degradation and delayed activation of SAGs. Better antioxidant defense in chloroplasts at later stages of senescence was able to mitigate the deleterious effects of ROS in CMS plants. We propose that delayed increase in ROS in cytoplasmic male sterile wheat plants resulted in delayed activation of WRKY53, SAGs and the associated biochemical changes than fertile plants.

Expression of tyrosine hydroxylase in CD4+ T cells contributes to alleviation of Th17/Treg imbalance in collagen-induced arthritis.

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Wang, Xiao-Qin; Liu, Yan; Cai, Huan-Huan; Peng, Yu-Ping; Qiu, Yi-Hua

2016-12-01

Tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines, is expressed in T lymphocytes. However, the role of T cell-expressed TH in rheumatoid arthritis (RA) is less clear. Herein, we aimed to show the contribution of TH expression by CD4 + T cells to alleviation of helper T (Th)17/regulatory T (Treg) imbalance in collagen-induced arthritis (CIA), a mouse model of RA. CIA was prepared by intradermal injection of collagen type II (CII) at tail base of DBA1/J mice. Expression of TH in the spleen and the ankle joints was measured by real-time polymerase chain reaction and Western blot analysis. Percentages of TH-expressing Th17 and Treg cells in splenic CD4 + T cells were determined by flow cytometry. Overexpression and knockdown of TH gene in CD4 + T cells were taken to evaluate effects of TH on Th17 and Treg cells in CIA. TH expression was upregulated in both the inflamed tissues (spleen and ankle joints) and the CD4 + T cells of CIA mice. In splenic CD4 + T cells, the cells expressing TH were increased during CIA. These cells that expressed more TH in CIA were mainly Th17 cells rather than Treg cells. TH gene overexpression in CD4 + T cells from CIA mice reduced Th17 cell percentage as well as Th17-related transcription factor and cytokine expression and secretion, whereas TH gene knockdown enhanced the Th17 cell activity. In contrast, TH gene overexpression increased Treg-related cytokine expression and secretion in CD4 + T cells of CIA mice, while TH gene knockdown decreased the Treg cell changes. Collectively, these findings show that CIA induces TH expression in CD4 + T cells, particularly in Th17 cells, and suggest that the increased TH expression during CIA represents an anti-inflammatory mechanism.

Design of a MEMS Capacitive Comb-drive Micro-accelerometer with Sag Optimization

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B. D. PANT

2009-10-01

Full Text Available The current paper presents an optimization study for the designing of a highly sensitive inertial grade capacitive accelerometer based on comb-drive actuation and sensing. The proof mass, suspension system (beams or tethers, stators and rotors have to be realized through an HAR (high aspect ratio DRIE (deep reactive ion etching process for which process optimization has already been done at our laboratory. As the proof mass is a bulk micro-machined structure having a mass in milligram range, the optimum positioning of the tethers on the proof mass is important to have minimum sag, necessary to reduce the off-axis sensitivity. The optimization for the positioning of the tethers has been carried out using a commercial software tool ANSYSTM Multiphysics. The accelerometer has been modeled analytically to predict its characteristics. The dependency of sensitivity on the dimensions of the suspension beams (tethers has also been verified using the above FEM software tool. The present device has been designed to deliver a high sensitivity of 13.6 mV/g/V for low-g applications.

Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells.

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Cyndi Chen

Full Text Available BACKGROUND: Both naturally arising Foxp3(+ and antigen-induced Foxp3(- regulatory T cells (Treg play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel class II MHC tetramer, we have isolated a population of CD4(+ Foxp3(- T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells from diabetes-resistant non-obese resistant (NOR mice. These Foxp3(- NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. CONCLUSIONS/SIGNIFICANCE: These studies identified a unique population of autoantigen-specific Foxp3(- Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.

CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

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McNally, Alice; Hill, Geoffrey R.; Sparwasser, Tim; Thomas, Ranjeny; Steptoe, Raymond J.

2011-01-01

CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion. PMID:21502514

Impact of distributed generation in the probability density of voltage sags; Impacto da geracao distribuida na densidade de probabilidade de afundamentos de tensao

Energy Technology Data Exchange (ETDEWEB)

Ramos, Alessandro Candido Lopes [CELG - Companhia Energetica de Goias, Goiania, GO (Brazil). Generation and Transmission. System' s Operation Center], E-mail: alessandro.clr@celg.com.br; Batista, Adalberto Jose [Universidade Federal de Goias (UFG), Goiania, GO (Brazil)], E-mail: batista@eee.ufg.br; Leborgne, Roberto Chouhy [Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, RS (Brazil)], E-mail: rcl@ece.ufrgs.br; Emiliano, Pedro Henrique Mota, E-mail: ph@phph.com.br

2009-07-01

This article presents the impact of distributed generation in studies of voltage sags caused by faults in the electrical system. We simulated short-circuit-to-ground in 62 lines of 230, 138, 69 and 13.8 kV that are part of the electrical system of the city of Goiania, of Goias state . For each fault position was monitored the bus voltage of 380 V in an industrial consumer sensitive to such sags. Were inserted different levels of GD near the consumer. The simulations of a short circuit, with the monitoring bar 380 V, were performed again. A study using stochastic simulation Monte Carlo (SMC) was performed to obtain, at each level of GD, the probability curves and sags of the probability density and its voltage class. With these curves were obtained the average number of sags according to each class, that the consumer bar may be submitted annually. The simulations were performed using the Program Analysis of Simultaneous Faults - ANAFAS. In order to overcome the intrinsic limitations of the methods of simulation of this program and allow data entry via windows, a computational tool was developed in Java language. Data processing was done using the MATLAB software.

Glucocorticoid-induced TNF receptor family related protein ligand [GITR-L] is requisite for optimal functioning of regulatory CD4+ T cells.

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Gongxian eLiao

2014-02-01

Full Text Available Glucocorticoid-Induced Tumor necrosis factor Receptor family-related protein (GITR, TNFRSF18, CD357 is constitutively expressed on regulatory T cells (Tregs and is inducible on effector T cells (Teffs. In this report, we examine the role of GITR-Ligand (GITR-L, which is expressed by antigen presenting cells, on the development and expansion of Tregs. We found that GITR-L is dispensable for the development of naturally occurring FoxP3+ Treg cells in the thymus. However, the expansion of Treg in GITR-L-/- mice is impaired after injection of the dendritic cells (DCs inducing factor Flt3 ligand. Furthermore, DCs from the liver of GITR-L-/- mice were less efficient in inducing proliferation of antigen-specific Treg cells in vitro than the same cells from WT littermates. Upon gene transfer of ovalbumin into hepatocytes of GITR-L-/- FoxP3(GFP reporter mice using adeno-associated virus (AAV8-OVA the number of antigen-specific Treg in liver and spleen is reduced. The reduced number of Tregs resulted in an increase in the number of ovalbumin specific CD8+ T effector cells. This is highly significant because proliferation of antigen specific CD8+ cells itself is dependent on the presence of GITR-L, as shown by in vitro experiments and by adoptive transfers into GITR-L-/-Rag-/- and Rag-/- mice that had received AAV8-OVA. Surprisingly, administering αCD3 significantly reduced the numbers of FoxP3+ Treg cells in the liver and spleen of GITR-L-/- but not WT mice. Because soluble Fc-GITR-L partially rescues αCD3 induced in vitro depletion of the CD103+ subset of FoxP3+CD4+ Treg cells, we conclude that expression of GITR-L by antigen presenting cells is requisite for optimal Treg-mediated regulation of immune responses including those in response during gene transfer.

IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

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Salamon, P; Shefler, I; Moshkovits, I; Munitz, A; Horwitz Klotzman, D; Mekori, Y A; Hershko, A Y

2017-11-01

We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs in vitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis. © 2017 John Wiley & Sons Ltd.

[Zaocys type II collagen regulates mesenteric lymph node Treg/Th17 cell balance in mice with collagen-induced arthritis].

Science.gov (United States)

Wang, Hao; Feng, Zhitao; Zhu, Junqing; Li, Juan

2014-05-01

To investigate the effect of oral administration of Zaocys type II collagen (ZCII) on the percentages of Treg/Th17 cells in mesenteric lymph node lymphocytes (MLNLs) in mice with collagen-induced arthritis (CIA). CIA was induced in male C57BL/6 mice by immunization with chicken type II collagen. Three weeks later, ZCII, purified by pepsin digestion, was orally administered in the mice for 7 consecutive days (daily dose of 10, 20, or 40 µg/kg). The severity of arthritis in each limb was evaluated using a macroscopic scoring system, and histopathological changes of the joint were observed microscopically with HE staining. The percentages of Treg and Th17 cells in MLNLs was detected by flow cytometry, and the levels of transforming growth factor-β (TGF-β) and interleukin-17 (IL-17) in the supernatant of MLNLs were measured by enzyme-linked immunosorbent assay. Compared with normal control mice, the mice with CIA had significantly higher scores for arthritis and histopathological changes, with also significantly increased percentages of Treg and Th17 cells in MLNLs and elevated levels of TGF-β and IL-17 in MLNL supernatant (P<0.05). In ZCII peptide-treated mice, the scores for arthritis and histopathological changes were significantly lower than those in CIA model group (P<0.05), and Treg cell percentage in MLNLs was up-regulated while Th17 cell percentage lowered; the level of TGF-β was increased but IL-17 was decreased significantly (P<0.05). Oral administration of ZCII improves CIA in mice by regulating the percentages of Treg/Th17 cells and the cytokine levels in MLNLs, suggesting the value of ZCII as a promising candidate agent for treatment of rheumatoid arthritis.

Quantification of the gravity-dependent change in the C-arm image center for image compensation in fluoroscopic spinal neuronavigation.

Science.gov (United States)

Hariri, S; Abbasi, H R; Chin, S; Steinberg, G; Shahidi, R

2001-01-01

In the quest to develop a viable, frameless spinal navigation system, many researchers are utilizing the C-arm fluoroscope. However, there is a significant problem with the C-arm that must be quantified: the gravity-dependent sag effect resulting from the geometry of the C-arm and aggravated by the inequity of weight at each end of the C-arm. This study quantified the C-arm sag effect, giving researchers the protocol and data needed to develop a program that accounts for this distortion. The development of spinal navigation algorithms that account for the C-arm sag effect should produce a more accurate spinal navigation system.

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

Science.gov (United States)

Morse, Michael A; Hobeika, Amy C; Osada, Takuya; Berglund, Peter; Hubby, Bolyn; Negri, Sarah; Niedzwiecki, Donna; Devi, Gayathri R; Burnett, Bruce K; Clay, Timothy M; Smith, Jonathan; Lyerly, H Kim

2010-09-01

Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

Science.gov (United States)

Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

Interactions between Th1 cells and Tregs affect regulation of hepatic fibrosis in biliary atresia through the IFN-γ/STAT1 pathway.

Science.gov (United States)

Wen, Jie; Zhou, Ying; Wang, Jun; Chen, Jie; Yan, Wenbo; Wu, Jin; Yan, Junkai; Zhou, Kejun; Xiao, Yongtao; Wang, Yang; Xia, Qiang; Cai, Wei

2017-06-01

Regulatory T cells (Tregs) and CD4 + T helper (Th) cells have important roles in bile duct injury of biliary atresia (BA). However, their impacts on liver fibrosis are undefined. Between 2013 and 2016, 146 patients with various stages of BA were enrolled in this study. Peripheral blood, liver biopsy and lymph node samples were collected. Flow cytometry, magnetic cell sorting and immunostaining were used to characterize lymphocytes from BA patients. Deficiency of Tregs was observed along with increased Th1, Th2 and Th17 frequencies in the peripheral blood and livers of BA patients. The levels of peripheral and intrahepatic Th1 cells positively correlated with the stage of liver fibrosis. Furthermore, Th1 cells were located in close proximity to activated hepatic stellate cells (HSCs) and areas of fibrosis in BA livers. In culture, Th1 cells accelerated the proliferation and secretion of profibrogenic markers of HSCs through the IFN-γ/STAT1 pathway. Of note, Tregs blocked the Th1-stimulated effects on HSCs by inhibiting Th1-induced activation of STAT1. Consistent with the results of in vitro study, intrahepatic IFN-γ/STAT1 levels increased in relation to the severity of liver fibrosis in BA patients, and the altered balance between MMP2 and TIMP1 expressions in livers may contribute to increased deposition of extracellular matrix and fibrosis. Finally, to identify the effects of Th1 cells on Tregs, we demonstrated that Th1 cells upregulated the proportion of aTreg cells by secreting IFN-γ cytokine. Thus, aberrant Th1 immune responses in BA promote the proliferation and secretion of HSCs through the IFN-γ/STAT1 pathway. The regulation of HSCs by the interactions between Tregs and Th1 cells might be part of the mechanism underlying progressive liver fibrosis and may be a suitable target for therapy.

Semi-Active Control of Three-Dimensional Vibrations of an Inclined Sag Cable with Magnetorheological Dampers

DEFF Research Database (Denmark)

Zhou, Q.; Nielsen, Søren R.K.; Qu, W. L.

2006-01-01

Three-dimensional semi-active vibration control of an inclined sag cable with discrete magnetorheological (MR) dampers is investigated in this paper using the finite difference method (FDM). A modified Dahl model is used to describe the dynamic property of MR damper. The nonlinear equations...

Thermal expansion of beryllium oxide

International Nuclear Information System (INIS)

Solodukhin, A.V.; Kruzhalov, A.V.; Mazurenko, V.G.; Maslov, V.A.; Medvedev, V.A.; Polupanova, T.I.

1987-01-01

Precise measurements of temperature dependence of the coefficient of linear expansion in the 22-320 K temperature range on beryllium oxide monocrystals are conducted. A model of thermal expansion is suggested; the range of temperature dependence minimum of the coefficient of thermal expansion is well described within the frames of this model. The results of the experiment may be used for investigation of thermal stresses in crystals

All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

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Ling Lu

Full Text Available 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.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.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.

Improving Energy Efficiency Via Optimized Charge Motion and Slurry Flow in Plant Scale Sag Mills

Energy Technology Data Exchange (ETDEWEB)

Raj K. Rajamani

2006-07-21

A research team from the University of Utah is working to make inroads into saving energy in these SAG mills. In 2003, Industries of the Future Program of the Department of Energy tasked the University of Utah team to build a partnership between the University and the mining industry for the specific purpose of reducing energy consumption in SAG mills. A partnership was formed with Cortez Gold Mines, Outokumpu Technology, Kennecott Utah Copper Corporation, and Process Engineering Resources Inc. At Cortez Gold Operations the shell and pulp lifters of the semiautogenous grinding mill was redesigned. The redesigned shell lifter has been in operation for over three years and the redesigned pulp lifter has been in operation for over nine months now. This report summarizes the dramatic reductions in energy consumption. Even though the energy reductions are very large, it is safe to say that a 20% minimum reduction would be achieved in any future installations of this technology.

Cytokine Gene Expression in Response to SnSAG1 in Horses with Equine Protozoal Myeloencephalitis

Science.gov (United States)

Spencer, Jennifer A.; Deinnocentes, Patricia; Moyana, Edith M.; Guarino, Anthony J.; Ellison, Siobhan E.; Bird, R. Curtis; Blagburn, Byron L.

2005-01-01

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. β-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-γ production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease. PMID:15879026

FOXP3 renders activated human regulatory T cells resistant to restimulation-induced cell death by suppressing SAP expression.

Science.gov (United States)

Katz, Gil; Voss, Kelsey; Yan, Toria F; Kim, Yong Chan; Kortum, Robert L; Scott, David W; Snow, Andrew L

2018-05-01

Restimulation-induced cell death (RICD) is an apoptotic program that regulates effector T cell expansion, triggered by repeated stimulation through the T cell receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4 + regulatory T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3 (FOXP3) transcription factor, although the mechanism remains unclear. T cells from patients with X-linked lymphoproliferative disease (XLP-1), that lack the adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD. Here we demonstrate that normal Tregs express very low levels of SAP compared to conventional T cells. FOXP3 reduces SAP expression by directly binding to and repressing the SH2D1A (SAP) promoter. Indeed, ectopic SAP expression restores RICD sensitivity in human FOXP3 + Tregs. Our findings illuminate the mechanism behind FOXP3-mediated RICD resistance in Tregs, providing new insight into their long-term persistence. Published by Elsevier Inc.

Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(posCD25(high T cells for immunotherapy.

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Jorieke H Peters

Full Text Available BACKGROUND: Regulatory T cell (Treg based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(posCD25(high Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants.

Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer.

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Mia Kim

Full Text Available BACKGROUND: Regulatory T cells (Treg expressing the transcription factor forkhead-box protein P3 (Foxp3 have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC. METHODS AND FINDINGS: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. CONCLUSIONS: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression.

The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway

NARCIS (Netherlands)

Leito, Jelani T. D.; Ligtenberg, Antoon J. M.; van Houdt, Michel; van den Berg, Timo K.; Wouters, Diana

2011-01-01

Salivary agglutinin (SAG), also known as gp-340 and Deleted in Malignant Brain Tumours 1, is a glycoprotein that is present in tears, lung fluid and mucosal surfaces along the gastrointestinal tract. It is encoded by the Deleted in Malignant Brain Tumours 1 gene, a member of the Scavenger Receptor

T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible.

Science.gov (United States)

Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Schwab, Nicholas; Wiendl, Heinz

2009-08-01

CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA-G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T cell proliferation in vitro, suggesting their role in immune regulation. We here characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous HLA-G(neg) T(resp) function. Using a suppression system free of APC, we demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg) T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression is independent of cell-cell contact and is reversible, as the removal of HLA-G(pos) T(reg) from the established coculture restored the proliferative capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression critically depends on the secretion of IL-10 but not TGF-beta.

Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation.

Science.gov (United States)

Lin, Fang; Luo, Xuerui; Tsun, Andy; Li, Zhiyuan; Li, Dan; Li, Bin

2015-10-01

Kaempferol is a natural flavonoid found in many vegetables and fruits. Epidemiologic studies have described that Kaempferol intake could reduce risk of cancer, especially lung, gastric, pancreatic and ovarian cancers. Recent studies have shown that Kaempferol could also be beneficial to the body to defend against inflammation, and infection by bacteria and viruses; however, the molecular mechanism of its immunoregulatory function remains largely unknown. Through screening a small molecule library of traditional Chinese medicine (TCM), we identified that Kaempferol could enhance the suppressive function of regulatory T cells (Tregs). Kaempferol was found to increase FOXP3 expression level in Treg cells and prevent pathological symptoms of collagen-induced arthritis in a rat animal model. Kaempferol could also reduce PIM1-mediated FOXP3 phosphorylation at S422. Our study reveals a molecular mechanism that underlies the anti-inflammatory action of Kaempferol for the prevention and treatment of inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

DEFF Research Database (Denmark)

Krejsgaard, T; Gjerdrum, L M; Ralfkiaer, E

2008-01-01

Sézary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3...... in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress...... the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF...

Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

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Sudipta Tripathi

2015-02-01

Full Text Available Tolerance of the fetus by the maternal immune system is regulated through various mechanisms involving the different immune cells, both in the periphery and locally at the feto-maternal interface. The maternal T lymphocytes are aware of the paternal fetal antigens and a state of dynamic T cell homeostasis is maintained in the uterus during gestation, which involves increase in antigen-specific regulatory T cell (Treg proliferation, increase in apoptosis of antigen-specific effector T cells, and inhibition of excessive inflammation post successful implantation to ensure tolerance to the fetus. The Tregs play an important role in the maintenance of tolerance during gestation. Recently, the inflammatory T helper type 17 (Th17 cells are reported to have a role in loss of tolerance to the fetus. The interaction between costimulatory molecule programmed death 1 (PD1 and its ligand PDL1 is known to play a role in regulating both the Tregs and Th17 cells. Here we discuss how the PD1/PDL1 pathway affects these two T cell populations and its role in feto-maternal tolerance.

An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

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Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

2018-04-19

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo.

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Yin-Ping Jia

Full Text Available Toll-like receptors (TLRs 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.

3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation.

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Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

2017-02-10

Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis. Here we demonstrated that 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen. In vitro, BrPA facilitated the differentiation of Treg cells, suppressed Th17 cells, and inhibited the activation of DCs. These results suggested that BrPA may be a therapeutic target of murine arthritis. Although the role of IL-17 is not clarified in the treatment of RA, targeting cell metabolism to alter the immune cell functions might lead to a new therapeutic strategy for RA.

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

OpenAIRE

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.

An Enhanced LVRT Scheme for DFIG-based WECSs under Both Balanced and Unbalanced Grid Voltage Sags

DEFF Research Database (Denmark)

Mohammadi, Jafar; Afsharnia, Saeed; Ebrahimzadeh, Esmaeil

2017-01-01

reactive power into the grid. The passive compensator is based on a three-phase stator damping resistor (SDR) located in series with the stator windings. The proposed scheme decreases the negative effects of grid voltage sags in the DFIG system including the rotor over-currents, electromagnetic torque...

Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients

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Jie Wang

2018-01-01

Full Text Available Background/Aims: To investigate the changes in peripheral blood Treg/Th17 cell balance and its significance in patients with chronic renal failure (CRF and cognitive impairment. Methods: A total of 71 patients with CRF were enrolled as a study group. The patients were divided into a cognitive impairment group and a normal cognitive function group according to the Mini-Mental State Examination (MMSE. Peripheral blood Treg and Th17 cells were analyzed by flow cytometry and their relevant cytokines (IL-17, IL-10 and TGF-β and other biochemical indicators, including C-reactive protein (CRP and IL-6, were determined by ELISA. Results: Thepatients with both CRF and cognitive impairment were older than the cognitive normal groups. Peripheral blood Treg cells by Flow cytometry (the CRF cognitive impairment group 5.57±1.3%, CRF group with normal cognitive function 7.5 ± 0.9% and normal control group 9.7 ± 1.7%,P<0.05 and its related cytokines (IL-10 and TGF-β by ELISA detection were lower in the group with cognitive impairment than in the group without cognitive impairment ( IL-10, 7.4±4.2 pg/mL, 13.8±3.9 pg/mL, 18.3±3.2 pg/mL; TGF-β 335.6±175.3 pg/mL, 512.7 ± 114.6 pg/mL, 953.8±373.4 pg/mL P < 0.05, respectively.However, Th17 cell numbers (the CRF cognitive impairment group 3.3 ± 0.7%, CRF group with normal cognitive function2.2 ± 0.5% and normal control group 1.5 ± 0.3%,and cytokine levels (IL-17, IL-6 and CRP were higher in the group with cognitive impairment IL-6 (21.3 ± 5.1 pg/mL, IL-17 (18.5 ± 4.2 pg/mL and CRP (20.3 ± 5.9 mg/L in the CRF group with cognitive impairment when compared with the CRF group and normal cognitive function (12.2 ± 4.5 pg/mL, 12.1 ± 3.7 pg/mL and 13.5 ± 4.6 mg/L, respectively or the normal control group (9.2 ± 5.8 pg/mL, 7.4 ± 2.6 pg/mL and 3.2 ± 1.3 mg/L, respectively, P<0.05. The frequencies of Treg in patients with CRF were positively correlated with the MMSE scores ((r = 0.518, P < 0.05, but the

Comparison of the effects of SAG-M and whole-blood transfusions on postoperative suppression of delayed hypersensitivity

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

1991-01-01

The influence of perioperative whole-blood transfusion and transfusion with erythrocyte suspension (SAG-M blood) on postoperative depression of cell-mediated immunity (CMI) was investigated in 67 patients who underwent elective resection for colorectal cancer. Cell-mediated immunity was assessed...

Acute viral hepatitis in adults. Comparison of the radioimmunoassay and counterimmunoelectrophoresis methods of detecting HB/sub s/Ag

International Nuclear Information System (INIS)

Wenzel, R.P.; Teates, C.D.; Galapon, Q.; Barczak, R.; Ling, C.M.; Overby, L.R.

1975-01-01

The radioimmunoassay (RIA) and counterimmunoelectrophoretic (CIE) methods were compared in detecting hepatitis B antigen (HB/sub s/Ag) in 407 acute and 336 convalescent sera of adults with viral hepatitis. The CIE method demonstrated that 41 percent of acute and 28 percent of 14- to 17-day serum specimens were HB/sub s/Ag-positive. The RIA method demonstrated seropositivity in 60 percent of acute and 56 percent of convalescent specimens (P less than .001). Eighty-four percent of coded specimens initially positive for HB/sub s/Ag by RIA were found to have subtype antigenic determinants d or y; 92 percent of the HB/sub s/Ag-negative controls were negative for subtype antigens, confirming the specificity of the RIA test. RIA subtyping data corroborated earlier work with immunodiffusion techniques. (U.S.)

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

International Nuclear Information System (INIS)

Yang, Xia; Qian, Feng; He, Hai-Yang; Liu, Kai-Jun; Lan, Yuan-Zhi; Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang

2011-01-01

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4 + and CD8 + T cells, especially the CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro

Dynamics of antigen presentation to transgene product-specific CD4+ T cells and of Treg induction upon hepatic AAV gene transfer

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George Q Perrin

2016-01-01

Full Text Available The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4+ T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8 vector expressing cytoplasmic ovalbumin (OVA into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. We find that that the liver-draining lymph nodes (celiac and portal are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4+ T cells (requiring professional antigen-presenting cells, e.g., macrophages and CD4+CD25+FoxP3+ Treg induction. Antigen presentation in the liver itself contributes to activation of CD4+ T cells egressing from the liver. Hepatic-induced Treg rapidly disseminate through the systemic circulation. By contrast, a secreted OVA transgene product is presented in multiple organs, and OVA-specific Treg emerge in both the thymus and periphery. In summary, liver draining lymph nodes play an integral role in hepatic antigen presentation and peripheral Treg induction, which results in systemic regulation of the response to viral gene products.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

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Yang, Xia [Institute of Immunology,Third Military Medical University, Chongqing (China); Qian, Feng [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); He, Hai-Yang; Liu, Kai-Jun [Institute of Immunology,Third Military Medical University, Chongqing (China); Lan, Yuan-Zhi [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang [Institute of Immunology,Third Military Medical University, Chongqing (China)

2011-12-02

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4{sup +} and CD8{sup +} T cells, especially the CD4{sup +}CD25{sup +}Foxp3{sup +} Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia.

Science.gov (United States)

Shimazu, Yayoi; Shimazu, Yutaka; Hishizawa, Masakatsu; Hamaguchi, Masahide; Nagai, Yuya; Sugino, Noriko; Fujii, Sumie; Kawahara, Masahiro; Kadowaki, Norimitsu; Nishikawa, Hiroyoshi; Sakaguchi, Shimon; Takaori-Kondo, Akifumi

2016-02-01

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1. Because of its immunosuppressive property and resistance to treatment, patients with ATL have poor prognoses. ATL cells possess the regulatory T cell (Treg) phenotype, such as CD4 and CD25, and usually express forkhead box P3 (FOXP3). However, the mechanisms of FOXP3 expression and its association with Treg-like characteristics in ATL remain unclear. Selective demethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 gene leads to stable FOXP3 expression and defines natural Tregs. Here, we focus on the functional and clinical relationship between the epigenetic pattern of the TSDR and ATL. Analysis of DNA methylation in specimens from 26 patients with ATL showed that 15 patients (58%) hypomethylated the TSDR. The FOXP3(+) cells were mainly observed in the TSDR-hypomethylated cases. The TSDR-hypomethylated ATL cells exerted more suppressive function than the TSDR-methylated ATL cells. Thus, the epigenetic analysis of the FOXP3 gene identified a distinct subtype with Treg properties in heterogeneous ATL. Furthermore, we observed that the hypomethylation of TSDR was associated with poor outcomes in ATL. These results suggest that the DNA methylation status of the TSDR is an important hallmark to define this heterogeneous disease and to predict ATL patient prognosis. ©2015 American Association for Cancer Research.

[Effect of Electroacupuncture Stimulation of "Guanyuan" (CV 4) and "Zusanli" (ST 36) on Spleen Lymphocytes Treg/Th 17 Immune Balance in Ulcerative Colitis Mice].

Science.gov (United States)

Wang, Cheng-yu-lin; Zeng, Lin-lan; Geng, Yu; Wang, Xiang; Zhang, He-jiao; Yang, Hui; Wu, Qiao- feng; Yu, Shu-guang

2016-02-01

To observe the effect of electroacupuncture (EA) intervention on spleen T-helper 17 (Th 17) and regulatory T (Treg) cell levels in mice with ulcerative colitis (UC), so as to reveal its mechanisms underlying improvement of UC. METHODS Kunming mice were randomized into control, UC model and EA groups, with 8 mice in each group. The UC model was established by giving the mice with 3% Dextran Sulfate Sodium (DSS) for 5 days. EA (15 Hz/25 Hz, 0.1-0.2 mA) was applied at "Guanyuan" (CV 4) and bilateral "Zusanli" (ST 36, used alternatively) for 10 min, once a day for 5 days. The animals' disease activity index [DAl, = (body weight index score + stool score + bleeding score)/3; 0-4 points] were calculated. The pathological changes of colon tissues were observed by light microscopy after H. E. stain, and spleen Treg (CD⁴⁺ CD²⁵⁺ Foxp³⁺ Treg) and Th 17 (CD³⁺ CD⁸⁺ IL-17⁺ Th 17) lymphocyte levels were determined by flow cytometry. Compared to the control group, the DAl score and the ratio of Th 17/CD⁸⁺ T cells were significantly increased, while the ratio of Treg/CD⁴⁺ T cells obviously decreased in the model group (P Th 17/CD⁸⁺ T cells and the decreased Treg/CD⁴⁺ T cells were reversed (P Th 17 lymphocytes.

Study of southern CHAONAN sag lower continental slope basin deposition character in Northern South China Sea

Science.gov (United States)

Tang, Y.

2009-12-01

Northern South China Sea Margin locates in Eurasian plate,Indian-Australia plate,Pacific Plates.The South China Sea had underwent a complicated tectonic evolution in Cenozoic.During rifting,the continental shelf and slope forms a series of Cenozoic sedimentary basins,including Qiongdongnan basin,Pearl River Mouth basin,Taixinan basin.These basins fill in thick Cenozoic fluviolacustrine facies,transitional facies,marine facies,abyssal facies sediment,recording the evolution history of South China Sea Margin rifting and ocean basin extending.The studies of tectonics and deposition of depression in the Southern Chaonan Sag of lower continental slope in the Norther South China Sea were dealt with,based on the sequence stratigraphy and depositional facies interpretation of seismic profiles acquired by cruises of“China and Germany Joint Study on Marine Geosciences in the South China Sea”and“The formation,evolution and key issues of important resources in China marginal sea",and combining with ODP 1148 cole and LW33-1-1 well.The free-air gravity anomaly of the break up of the continental and ocean appears comparatively low negative anomaly traps which extended in EW,it is the reflection of passive margin gravitational effect.Bouguer gravity anomaly is comparatively low which is gradient zone extended NE-SW.Magnetic anomaly lies in Magnetic Quiet Zone at the Northern Continental Margin of the South China Sea.The Cenozoic sediments of lower continental slope in Southern Chaonan Sag can be divided into five stratum interface:SB5.5,SB10.5,SB16.5,SB23.8 and Hg,their ages are of Pliocene-Quaternary,late Miocene,middle Miocene,early Miocene,paleogene.The tectonic evolution of low continental slope depressions can be divided into rifting,rifting-depression transitional and depression stages,while their depositional environments change from river to shallow marine and abyssa1,which results in different topography in different stages.The topographic evolvement in the study

Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia

Science.gov (United States)

Perez-Crespo, Ignacio; Chillón-Marinas, Carlos; Khoubbane, Messaoud; Quesada, Carla; Reguera-Gomez, Marta; Mas-Coma, Santiago; Fresno, Manuel; Gironès, Núria

2017-01-01

Background Fascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity. Methodology/Principal findings The experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. After 20 weeks of primary infection, PI did not present significant changes in the expression of those genes when compared to non-infected rats (NI), but an increase of Il4, Arg1 and Ifng mRNA in the spleen was observed in R12, suggesting the existence of an active mixed Th1/Th2 systemic immune response in reinfection. Foxp3, Il10, Tgfb and Ebi3 levels increased in the spleen in R12 when compared to NI and PI, indicating that the Treg gene expression levels are potentiated in chronic phase reinfection. Il17 gene expression levels in R12 in the spleen increased when compared to NI, PI and R8. Gene expression levels of Il10 in the thymus increased when compared to NI and PI in R12. Ifng expression levels in the thymus increased in all reinfected rats, but not in PI. The clinical phenotype was determined by the fluke burden, the rat body weight and the hemogram. Multivariate mathematical models were built to describe the Th1/Th2/Th17/Treg expression levels and the clinical phenotype. In reinfection, two phenotypic patterns were detected: i) one which includes only increased splenic Ifng

A sagging along the eastern Chianti Mts., Italy

Science.gov (United States)

Coltorti, M.; Ravani, S.; Cornamusini, G.; Ielpi, A.; Verrazzani, F.

2009-11-01

A deep-seated gravitational slope deformation (DGSD) affects the eastern side of the Chianti Mts. Ridge. It develops in an N-S to NW-SE direction and is > 10 km wide and 3-4 km long. This area corresponds to the eastern side of a main antiform, characterised by east-verging folds and thrusts involving bedrock of the Mesozoic-Paleogene Tuscan Units, particularly sandstones containing interlayered highly fractured and deformed Ligurian rocks (shales and limestones with olistostromes). The foot of the slope is characterised by tilted Plio-Pleistocene deposits unconformably sealing the bedrock structures as folds, thrusts and faults. The most significant morphological features are a main escarpment, trenches, several secondary and counter-slope escarpments that together indicate large-scale gravitational phenomena. The main escarpment is responsible for the headward retreat of the slope, and is deeply segmented by numerous arcuate niches that reveal differential movements of single blocks. The DGSD is also dissected by SW-NE trending streams that often deepen inside the N-S trenches. Minor landslides due to local instability are also present. At the foot of the slope, the older continental Pliocene deposits of the Upper Valdarno Basin crop out. Although tilted by tectonic movements, the deposits have not been severely affected by gravitational deformations. This indicates that the movement is a typical sagging, a large landslide at an embryonic stage, affecting the upper part of the slope but not reaching the valley bottom. The deformations are absorbed in the rock mass which is also partially drained by stream incision that prevents high pore pressure. The occurrence of down-slope and down-movement facing escarpments and up-slope and up-movement facing counter-slope escarpments indicate a sagging characterised by a listric spoon-shaped geometry. The DGSD has a style similar to crustal extensional tectonics such as Morton and Black's crustal attenuation model. Although

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

Science.gov (United States)

Soria, I; López-Relaño, J; Viñuela, M; Tudela, J-I; Angelina, A; Benito-Villalvilla, C; Díez-Rivero, C M; Cases, B; Manzano, A I; Fernández-Caldas, E; Casanovas, M; Palomares, O; Subiza, J L

2018-04-01

Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4 + CD25 high FOXP3 + Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45 + MHC-II + ) cells obtained from the sublingual mucosa, including DCs (CD11b + ) and macrophages (CD64 + ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3 + Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells. © 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.

Analysis of changes in sagging type ST-T segment induced by exercise. Assessment of regional myocardial blood flow using quantitative 13NH3 positron emission tomography

International Nuclear Information System (INIS)

Watanabe, Takuya; Akutsu, Yasushi; Okazaki, Osamu

1995-01-01

Regional myocardial blood flow (RMBF) associated with exercise-induced ST depression was assessed using 13 NH 3 positron emission tomography (PET) to determine the significance of horizontal and sagging type ST segments. The subjects were 25 patients with angina pectoris, 25 patients with myocardial infarction, and 5 healthy male volunteers. Eleven regions of interests (ROI) were prepared to calculate RMBF. ST segments were unchanged in 27 patients (Group A) and were depressed in 23 patients (Group B). A 10% increase in RMBF was significantly observed in Group A (74.1%) than Group B (34.8%). In Group B, ST depression was divided into horizontal type (8 patients) and sagging type (15 patients). According to the type of ST depression, RMBF was increased by 10% or more in 50% (4/8) for horizontal type and in 26.7% (4/15) for sagging type. These findings suggested that unfavorable increase in RMBF in stenosiss-related coronary vessels may contribute to the development of ST depression induced by exercise. A constant increase in RMBF in all ROIs, including those with unfavorable RMBF increase, may be involved in the occurrence of horizontal type ST depression; sagging type ST depression may, however, occur by an increased difference in blood flow between unfavorable and favorable RMBF. (N.K.)

Late engagement of CD86 after influenza virus clearance promotes recovery in a FoxP3+ regulatory T cell dependent manner.

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Emily K Moser

2014-08-01

Full Text Available Influenza A virus (IAV infection in the respiratory tract triggers robust innate and adaptive immune responses, resulting in both virus clearance and lung inflammation and injury. After virus clearance, resolution of ongoing inflammation and tissue repair occur during a distinct recovery period. B7 family co-stimulatory molecules such as CD80 and CD86 have important roles in modulating T cell activity during the initiation and effector stages of the host response to IAV infection, but their potential role during recovery and resolution of inflammation is unknown. We found that antibody-mediated CD86 blockade in vivo after virus clearance led to a delay in recovery, characterized by increased numbers of lung neutrophils and inflammatory cytokines in airways and lung interstitium, but no change in conventional IAV-specific T cell responses. However, CD86 blockade led to decreased numbers of FoxP3+ regulatory T cells (Tregs, and adoptive transfer of Tregs into αCD86 treated mice rescued the effect of the blockade, supporting a role for Tregs in promoting recovery after virus clearance. Specific depletion of Tregs late after infection mimicked the CD86 blockade phenotype, confirming a role for Tregs during recovery after virus clearance. Furthermore, we identified neutrophils as a target of Treg suppression since neutrophil depletion in Treg-depleted mice reduced excess inflammatory cytokines in the airways. These results demonstrate that Tregs, in a CD86 dependent mechanism, contribute to the resolution of disease after IAV infection, in part by suppressing neutrophil-driven cytokine release into the airways.

METODOLOGÍA GENERAL PARA CORRELACIONAR SAGS CON EVENTOS AMBIENTALES U OPERATIVOS DEL SISTEMA DE DISTRIBUCIÓN

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Alejandro Castillo Guasca

2013-07-01

Full Text Available Es de gran importancia conocer cuáles son las causas  para que se presenten sags en las barrajes de distribución, debido a que la afectación sobre los clientes industriales es de carácter relevante. Por esta razón se planteó  una metodología para buscar la correlación existente entre sags y los eventos ambientales u operativos del sistema de distribución. A manera de ejemplo, se aplicó en tres subestaciones, las cuales se encuentran ubicadas en diferentes sectores de la ciudad. Para el desarrollo de esta metodología, se realizó la correlación de los datos mediante la implementación de tablas dinámicas y programación en Access, donde se evidenció qué tipo de eventos son los que tienen un mayor impacto sobre los clientes. De acuerdo a los resultados obtenidos se sugiere algunas recomendaciones para mitigar este tipo de eventos en el sistema de distribución.

Characteristics of Young Adults Enrolled Through the Affordable Care Act-Dependent Coverage Expansion.

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Han, Xuesong; Zhu, Shiyun; Jemal, Ahmedin

2016-12-01

The purpose of this study was to examine sociodemographic and health care-related characteristics of young adults covered through the Affordable Care Act (ACA)-dependent coverage expansion. Our sample consisted of 36,802 young adults aged 19-25 years from 2011 to 2014 National Health Interview Survey. Sociodemographic differences among young adults with the four insurance types were described: privately insured under parents, privately insured under self/spouse, publicly insured, and uninsured. Multivariable logistic models were fitted to compare those covered under parent with those covered through other traditional insurance types, in terms of the following outcomes: health status, health behaviors, insurance history and experience, access to care, care utilization, and receipt of preventive service, controlling for sociodemographic factors. Young adults who were covered under their parents' insurance were most likely to be college students and non-Hispanic whites. These young adults also had more stable insurance, better access to care, better care utilization patterns, and reported better health status, compared to their peers. The beneficiaries of the ACA-dependent coverage expansion were more likely to be college students from families with high socioeconomic status. Coverage under parents was associated with improved access to care and health outcomes among young adults. The enrollees through the ACA represent the healthiest subgroup of young adults and those with the best care utilization patterns, suggesting that the added cost relative to premium for insurers from this population will likely be minimal. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Novel Concept of CD4-Mediated Activation of Regulatory T Cells for the Treatment of Graft-Versus-Host Disease

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Janine Schlöder

2017-11-01

Full Text Available Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg, essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time- and cost-intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding human immunodeficiency virus-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time-intensive, and expensive in vitro expansion of isolated tTreg.

Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.

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Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun

2017-01-01

Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may

HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease.

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Li, Jun; Heinrichs, Jessica; Haarberg, Kelley; Semple, Kenrick; Veerapathran, Anandharaman; Liu, Chen; Anasetti, Claudio; Yu, Xue-Zhong

2015-07-15

Naturally derived regulatory T cells (Tregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of naturally derived regulatory T cells has been severely hampered by their scarce availability and nonselectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in preclinical models of bone marrow transplantation. We selected HY as a target Ag because it is a naturally processed, ubiquitously expressed minor histocompatibility Ag (miHAg) with a proven role in GVHD and GVL effect. We generated HY-specific iTregs (HY-iTregs) from resting CD4 T cells derived from TCR transgenic mice, in which CD4 cells specifically recognize HY peptide. We found that HY-iTregs were highly effective in preventing GVHD in male (HY(+)) but not female (HY(-)) recipients using MHC II-mismatched, parent→F1, and miHAg-mismatched murine bone marrow transplantation models. Interestingly, the expression of target Ag (HY) on the hematopoietic or nonhematopoietic compartment alone was sufficient for iTregs to prevent GVHD. Furthermore, treatment with HY-iTregs still preserved the GVL effect even against pre-established leukemia. We found that HY-iTregs were more stable in male than in female recipients. Furthermore, HY-iTregs expanded extensively in male but not female recipients, which in turn significantly reduced donor effector T cell expansion, activation, and migration into GVHD target organs, resulting in effective prevention of GVHD. This study demonstrates that iTregs specific for HY miHAgs are highly effective in controlling GVHD in an Ag-dependent manner while sparing the GVL effect. Copyright © 2015 by The American Association of Immunologists, Inc.

Mathematical modeling of the implications of dominant tolerance for tumor biology and the response to combination therapy

International Nuclear Information System (INIS)

Leon, Kalet; Garcia, Karina; Lage, Agustin

2008-01-01

The existence of regulatory T lymphocytes (Tregs) that can control effector lymphocytes within the context of autoimmune, infectious and tumoral diseases is definitely accepted in current immunological research. Tregs confirm the theory of dominant tolerance, which holds that the choice of antigen rejection or tolerance in the immune system is the result of a dynamic equilibrium between populations of effector and regulatory T lymphocytes. The present paper summarizes the result of a recent theoretical study using mathematical modeling to analyze the dynamic interplay between T lymphocyte populations in the absence or presence of tumors and in response to different therapeutic treatments. The resulting model, developed at the Center of Molecular Immunology, which received an award from the Cuban Academy of Sciences in 2002, includes tumor cells and can simulate the effect of antitumoral mono- or combination therapies, by taking into account the way in which certain dynamic properties of tumors can, under specific circumstances, lead to the spontaneous expansion of Tregs populations. One of the advantages of the model is the prediction of several new strategies for the differential treatment of tumors, depending upon their ability of inducing the expansion of regulatory T cells. This is the first model available for the study of the impact of Tregs on the growth of malignant tumors, with results supported by international publications. Additionally, the model predicts the practical effects of several combination therapies, including vaccines, the excision of the tumor and depletion of lymphocyte populations. (Author)

Analysis of equations of state and temperature dependence of thermal expansivity and bulk modulus for silicon

International Nuclear Information System (INIS)

Pandya, Tushar C; Bhatt, Apoorva D; Thakar, Nilesh A

2012-01-01

In the present paper an attempt has been made for the comparative study of different equations of state for silicon (Phase-1, cubic diamond structure) in the pressure range of 0-11 GPa. We compare the results of different equations of state (EOS) with available experimental data. The Kwon and Kim EOS is found to give far better agreement with the available experimental data. Results obtained by Poirier-Tarantola, Vinet, Tait and Suzuki's equations of state are not giving satisfactory agreement with the available experimental data. In the present study simple methods based on thermodynamic functions are presented to investigate the temperature dependence of thermal expansivity and bulk modulus for silicon. The results are reported for silicon. The calculated values of thermal expansivity are in good agreement with experimental data.

LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

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Islas-Vazquez, Lorenzo; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

2015-01-01

Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells. PMID:26582240

LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

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Lorenzo Islas-Vazquez

2015-01-01

Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

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Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

2017-05-01

Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Performance Improvement of DFIG Wind Turbine Using Series Grid-Side Converter under Unbalanced Grid Voltage and Voltage Sag Conditions

DEFF Research Database (Denmark)

Shokri, Yunes; Ebrahimzadeh, Esmaeil; Lesani, Hamid

2014-01-01

under unbalanced grid voltage and small voltage sag conditions without needing additional DC link capacitor or energy storage unlike other methods. The control system includes negative and positive sequence controllers which make the stator voltage balanced and keep it constant at the nominal value...

[Imiquimod combined with dendritic cell vaccine decreases Treg proportion and enhances anti-tumor responses in mice bearing melanoma].

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Ren, Shurong; Wang, Qiubo; Zhang, Yanli; Lu, Cuixiu; Li, Ping; Li, Yumei

2017-02-01

Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4). DC vaccine (OVA-DC) was prepared by overnight incubation of DCs added with chicken ovalbumin. C57BL/6 mice were separated into four groups which were treated with PBS, topical imiquimod application, OVA-DC intradermal injection and imiquimod plus OVA-DC, respectively. The tumor size was calculated by digital vernier caliper. Peripheral blood CD4 + FOXP3 + Tregs of the tumor-bearing mice was detected by flow cytometry. The cytotoxicity of splenic lymphocyte against B16-OVA was assessed in vitro by CCK-8 assay. Results Compared with the other three groups, B16-OVA-bearing mice treated with imiquimod plus DC vaccine had the smallest tumor volume. The percentage of CD4 + FOXP3 + Tregs decreased significantly in the combined treated mice. The combined treatment enhanced significantly cytotoxicity of splenic lymphocytes against B16-OVA cells. Conclusion Imiquimod combined with antigen-pulsed-DC vaccine could reduce CD4 + FOXP3 + Treg proportion and promote anti-tumor effect in mice with melanoma.

Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3

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Marc Beyer

2011-01-01

Full Text Available In recent years an increase of functional CD4+CD25+ regulatory T cells (Treg cells has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+CD25high Treg cells in patients with chronic lymphatic leukemia (CLL, multiple myeloma (MM as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS. In healthy individuals, low-level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with Treg cells. Here, we demonstrate that the expanded FOXP3+ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127low Treg cells and were strongly suppressive. A significant portion of CD127lowFOXP3+ Treg cells expressed only low levels of CD25 suggesting that the previously reported expansion of CD25+ Treg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4+CD127lowFOXP3+ Treg cells revealed an increase of both naïve as well as central and effector memory Treg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of Treg cells in malignant diseases.

Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

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Manuel Wiesinger

2017-10-01

Full Text Available In recent years, the exploration of regulatory T cell (Treg-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation of ex vivo expanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS® system, are ex vivo expanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i sterility testing, (ii assessment of Treg phenotype, (iii assessment of non-Treg cellular impurities, (iv confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various

Thermal expansion, anharmonicity and temperature-dependent Raman spectra of single- and few-layer MoSe₂ and WSe₂.

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Late, Dattatray J; Shirodkar, Sharmila N; Waghmare, Umesh V; Dravid, Vinayak P; Rao, C N R

2014-06-06

We report the temperature-dependent Raman spectra of single- and few-layer MoSe2 and WSe2 in the range 77-700 K. We observed linear variation in the peak positions and widths of the bands arising from contributions of anharmonicity and thermal expansion. After characterization using atomic force microscopy and high-resolution transmission electron microscopy, the temperature coefficients of the Raman modes were determined. Interestingly, the temperature coefficient of the A(2)(2u) mode is larger than that of the A(1g) mode, the latter being much smaller than the corresponding temperature coefficients of the same mode in single-layer MoS2 and of the G band of graphene. The temperature coefficients of the two modes in single-layer MoSe2 are larger than those of the same modes in single-layer WSe2. We have estimated thermal expansion coefficients and temperature dependence of the vibrational frequencies of MoS2 and MoSe2 within a quasi-harmonic approximation, with inputs from first-principles calculations based on density functional theory. We show that the contrasting temperature dependence of the Raman-active mode A(1g) in MoS2 and MoSe2 arises essentially from the difference in their strain-phonon coupling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study

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Sapna Thakur

2011-01-01

Full Text Available Background: Hepatocellular carcinoma (HCC is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH. Materials and Methods: The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005 and CH patients (2.88 ± 1.92, P < 0.005. Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05. Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05 compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.

Episodic normal faulting and magmatism during the syn-spreading stage of the Baiyun sag in Pearl River Mouth Basin: response to the multi-phase seafloor spreading of the South China Sea

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Deng, Peng; Mei, Lianfu; Liu, Jun; Zheng, Jinyun; Liu, Minghui; Cheng, Zijie; Guo, Fengtai

2018-03-01

Considerable post-breakup extensional deformation is recorded in the continental margins of the South China Sea (SCS). To recognize the nature and origin of the significant deformation during the syn-spreading stage (32-15.5 Ma) in the SCS, we comprehensively analyzed the geometry and kinematics of the faults and contemporaneous magmas in the Baiyun sag, northern margin of the SCS, using high-resolution regional three-dimensional seismic data. The kinematic analyses indicate that the faults in the Baiyun sag are recently formed following the onset of seafloor spreading in the SCS. The faults exhibit multiple episodes of growth history, with three active episodes, 32-29, 23.8-21 and 18.5-16.5 Ma, separated by periods of inactivity. Four volcanic groups comprising 98 volcanic mounds have been identified and described, located separately in the northwestern, the central, the southeastern and the northern slope areas. The occurrence of multiple palaeo-seafloors, complemented by the biostratigraphic and K-Ar dating data, reveals multiple extrusive events of the syn-spreading magmas in the Baiyun sag, with three active periods of 23.8-21, 18.5-17.5 and 17.5-16.5 Ma. This study confirms that the normal faulting has a shared genetic origin with the contemporaneous magmatism during the syn-spreading stage in the deep-offshore Baiyun sag, northern margin of the SCS. The episodic fault growth and magmatic extrusive events reveal that the Baiyun sag has undergone at least three episodic tectonic events during the syn-spreading stage, which evolved in response to the multi-stage seafloor spreading of the SCS.

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

Science.gov (United States)

Iman, Maryam; Rezaei, Ramazan; Azimzadeh Jamalkandi, Sadegh; Shariati, Parvin; Kheradmand, Farrah; Salimian, Jafar

2017-12-01

Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4 + T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.

Thermal-history reconstruction of the Baiyun Sag in the deep-water area of the Pearl River Mouth Basin, northern South China Sea

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Tang, Xiaoyin; Yang, Shuchun; Hu, Shengbiao

2017-11-01

The Baiyun Sag, located in the deep-water area of the northern South China Sea, is the largest and deepest subbasin in the Pearl River Mouth Basin and one of the most important hydrocarbon-accumulation depression areas in China. Thermal history is widely thought to be of great importance in oil and gas potential assessment of a basin as it controls the timing of hydrocarbon generation and expulsion from the source rock. In order to unravel the paleo-heat flow of the Baiyun Sag, we first analyzed tectonic subsidence of 55 pseudo-wells constructed based on newly interpreted seismic profiles, along with three drilled wells. We then carried out thermal modeling using the multi-stage finite stretching method and calibrated the results using collected present-day vitrinite reflectance data and temperature data. Results indicate that the first and second heating of the Baiyun Sag after 49 Ma ceased at 33.9 Ma and 23 Ma. Reconstructed average basal paleoheat flow values at the end of the rifting periods are 57.7-86.2 mW/m2 and 66.7-97.3 mW/m2, respectively. Following the last heating period at 23 Ma, the study area has undergone a persistent thermal attenuation phase, and basal heat flow has cooled down to 64.0-79.2 mW/m2 at present.

Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

Science.gov (United States)

Azevedo, Michelle de Campos Soriani; Marques, Heloisa; Binelli, Larissa Sarri; Malange, Mariana Silva Vieira; Devides, Amanda Carreira; Silva, Eliane Aparecida; Fachin, Luciana Raquel Vincenzi; Ghidella, Cassio Cesar; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Rosa, Patrícia Sammarco; Belone, Andrea de Farias Fernandes; Trombone, Ana Paula Favaro

2017-12-01

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis.

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Bei-Bei Zhang

Full Text Available Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson's trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01. Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01. This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice.

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression.

Science.gov (United States)

Wang, Mei; Chen, Bin; Sun, Xiao-Xian; Zhao, Xiang-Dong; Zhao, Yuan-Yuan; Sun, Li; Xu, Chang-Gen; Shen, Bo; Su, Zhao-Liang; Xu, Wen-Rong; Zhu, Wei

2017-12-01

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4 + T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME. Copyright © 2017 Elsevier Inc. All rights reserved.

Depletion of Treg cells inhibits minimal residual disease after surgery of HPV16-associated tumours

Czech Academy of Sciences Publication Activity Database

Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Rosalia, Rodney Alexander; Frič, Jan; Reiniš, Milan

2006-01-01

Roč. 29, č. 6 (2006), s. 1567-1571 ISSN 1019-6439 R&D Projects: GA ČR(CZ) GA301/04/0492 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * residual tumour disease * Treg cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.556, year: 2006

Shape, size and temperature dependency of thermal expansion ...

Indian Academy of Sciences (India)

M GOYAL

2018-05-19

May 19, 2018 ... Oriental J. Chem.32(4), 2193 (2016), is extended in the present study using Qi and Wang model [Mater. Chem. Phys. ... Nanomaterials; shape factor; size effect; thermal expansion; equation of state. ... als are different from that of their bulk material. ..... and 1c along with the present calculated results. It is.

Avaliação do antígeno SAG2a recombinante de Toxoplasma gondii como um potencial marcador diagnóstico para Toxoplasmose humana aguda

OpenAIRE

Béla, Samantha Ribeiro

2007-01-01

Proteínas recombinantes têm sido utilizadas para o diagnóstico sorológico da infecção por Toxoplasma gondii para diferenciar entre as fases aguda e crônica da toxoplasmose. Neste estudo, foi avaliada a reatividade de anticorpos IgG e IgG1 através de imunoensaios em soros de pacientes com toxoplasmose aguda e crônica dirigidos contra dois antígenos recombinantes clonados e expressos em E. coli, SAG2A (molécula recombinante total) e SAG2A(DELTA) (molécula recombinante deletada do...

Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

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Rohimah Mohamud

2017-12-01

Full Text Available Synthetic glycine coated 50 nm polystyrene nanoparticles (NP (PS50G, unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2 expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.

The beneficial effect of total glucosides of paeony on psoriatic arthritis links to circulating Tregs and Th1 cell function.

Science.gov (United States)

Wang, Yi Na; Zhang, Yu; Wang, Yan; Zhu, Ding Xian; Xu, Li Qin; Fang, Hong; Wu, Wei

2014-03-01

Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-γ and TNF-α), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ≥25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA. Copyright © 2013 John Wiley & Sons, Ltd.

Light-regulated leaf expansion in two Populus species: dependence on developmentally controlled ion transport.

Science.gov (United States)

Stiles, Kari A; Van Volkenburgh, Elizabeth

2002-07-01

Leaf growth responses to light have been compared in two species of Populus, P. deltoides and P. trichocarpa. These species differ markedly in morphology, anatomy, and dependence on light during leaf expansion. Light stimulates the growth rate and acidification of cell walls in P. trichocarpa but not in P. deltoides, whereas leaves of P. deltoides maintain growth in the dark. Light-induced growth is promoted in P. deltoides when cells are provided 50-100 mM KCl. In both species, light initially depolarizes, then hyperpolarizes mesophyll plasma membranes. However, in the dark, the resting E(m) of mesophyll cells in P. deltoides, but not in P. trichocarpa, is relatively insensitive to decade changes in external [K+]. Results suggest that light-stimulated leaf growth depends on developmentally regulated cellular mechanisms controlling ion fluxes across the plasma membrane. These developmental differences underlie species-level differences in growth and physiological responses to the photoenvironment.

Isotropic Negative Thermal Expansion Metamaterials.

Science.gov (United States)

Wu, Lingling; Li, Bo; Zhou, Ji

2016-07-13

Negative thermal expansion materials are important and desirable in science and engineering applications. However, natural materials with isotropic negative thermal expansion are rare and usually unsatisfied in performance. Here, we propose a novel method to achieve two- and three-dimensional negative thermal expansion metamaterials via antichiral structures. The two-dimensional metamaterial is constructed with unit cells that combine bimaterial strips and antichiral structures, while the three-dimensional metamaterial is fabricated by a multimaterial 3D printing process. Both experimental and simulation results display isotropic negative thermal expansion property of the samples. The effective coefficient of negative thermal expansion of the proposed models is demonstrated to be dependent on the difference between the thermal expansion coefficient of the component materials, as well as on the circular node radius and the ligament length in the antichiral structures. The measured value of the linear negative thermal expansion coefficient of the three-dimensional sample is among the largest achieved in experiments to date. Our findings provide an easy and practical approach to obtaining materials with tunable negative thermal expansion on any scale.

EFFECT OF LIPOSOMAL CLODRONATE-DEPENDENT DEPLETION OF PROFESSIONAL ANTIGEN PRESENTING CELLS ON NUMBERS AND PHENOTYPE OF CANINE CD4+CD25+FOXP3+ REGULATORY T CELLS

Science.gov (United States)

Weaver, Kriston F.; Stokes, John V.; Gunnoe, Sagen A.; Follows, Joyce S.; Shafer, Lydia; Ammari, Mais G.; Archer, Todd M.; Thomason, John M.; Mackin, Andrew J.; Pinchuk, Lesya M.

2015-01-01

Regulatory T cells (Tregs) are known to control autoreactivity during and subsequent to the development of the peripheral immune system. Professional antigen presenting cells (APCs), dendritic cells (DCs) and monocytes, have an important role in inducing Tregs. For the first time, this study evaluated proportions and phenotypes of Tregs in canine peripheral blood depleted of professional APCs, utilizing liposomal clodronate (LC) and multicolor flow cytometry analysis. Our results demonstrate that LC exposure promoted short term decreases followed by significant increases in the proportions or absolute numbers of CD4+CD25+FOXP3+ Tregs in dogs. In general, the LC-dependent Treg fluctuations were similar to the changes in the levels of CD14+ monocytes in Walker hounds. However, the proportions of monocytes showed more dramatic changes compared to the proportions of Tregs that were visually unchanged after LC treatment over the study period. At the same time, absolute Treg numbers showed, similarly to the levels of CD14+ monocytes, significant compensatory gains as well as the recovery during the normalization period. We confirm the previous data that CD4+ T cells with the highest CD25 expression were highly enriched for FOXP3. Furthermore, for the first time, we report that CD4+CD25lowFOXP3+ is the major regulatory T cell subset affected by LC exposure. The increases within the lowest CD25 expressers of CD4+FOXP3+ cells together with compensatory gains in the proportion of CD14+ monocytes during compensatory and normalization periods suggest the possible direct or indirect roles of monocytes in active recruitment and generation of Tregs from naïve CD4+ T cells. PMID:25950023

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb.

Science.gov (United States)

Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L

2017-01-17

FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.

CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

DEFF Research Database (Denmark)

Hartling, H J; Gaardbo, J C; Ronit, A

2012-01-01

The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24...... patients with HIV/HCV co-infection and 24 healthy individuals. CD4⁺ and CD8⁺ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4⁺ and CD8⁺ Tregs was found...... in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

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Maria Florencia Quiroga

Full Text Available 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.

Desequilíbrio imunológico periférico mediado por células Th17/Treg em pacientes com rinite alérgica

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Xuekun Huang

2014-04-01

Full Text Available Introdução: A rinite alérgica (RA é uma doença não infecciosa da mucosa nasal mediada por IgE após o contato com alérgenos. Objetivo: Investigar as células Th17 periféricas e CD4 + CD25 + Foxp3 + células T reguladoras (Treg e a expressão sérica de citocinas em pacientes com RA. Métodos: De março a maio de 2012, foi coletado o sangue periférico de 14 pacientes com RA (grupo RA e seis indivíduos saudáveis (grupo controle. A detecção das células Th17 e células Treg foi realizada através da citometria de fluxo e os níveis séricos de IL -17 e TGF- β1. Foram medidos por ELISA. Resultados: A percentagem de células Th17 no grupo RA foi bem maior do que no grupo controle (p < 0,01. A proporção de células Treg no grupo RA também foi drasticamente menor quando comparada ao grupo controle (p < 0,01. No grupo RA, o nível sérico de IL-17 foi significativamente maior do que no grupo controle (p < 0,01. Conclusão: O desequilíbrio de células Th17/Treg periféricas desempenha um papel importante na patogênese da RA.

Adoptive regulatory T cell therapy: challenges in clinical transplantation.

Science.gov (United States)

Safinia, Niloufar; Sagoo, Pervinder; Lechler, Robert; Lombardi, Giovanna

2010-08-01

The identification and characterisation of regulatory T cells (Tregs) has recently opened up exciting opportunities for Treg cell therapy in transplantation. In this review, we outline the basic biology of Tregs and discuss recent advances and challenges for the identification, isolation and expansion of these cells for cell therapy. Tregs of thymic origin have been shown to be key regulators of immune responses in mice and humans, preventing autoimmunity, graft-versus-host disease and organ graft rejection in the transplantation setting. To date, a variety of different methods to isolate and expand Tregs ex vivo have been advocated. Although promising, relatively few clinical trials of human Treg cell infusion have been initiated. Many key questions about Treg cell therapy still remain and here we provide an in-depth analysis and highlight the challenges and opportunities for immune intervention with Treg-based therapeutics in clinical transplantation.

Contribution of Mesenteric Lymph Nodes and GALT to the Intestinal Foxp3+ Regulatory T-Cell CompartmentSummary

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Duke Geem

2016-05-01

Full Text Available Background & Aims: Foxp3+ regulatory T cells (Tregs in the intestine promote immune tolerance to enteric antigens. Previous studies have shown that C-C chemokine receptor 7 (CCR7-dependent migration of intestinal dendritic cells to the mesenteric lymph nodes (mLN is involved in peripheral Foxp3+ Treg accumulation in the intestine and the establishment of oral tolerance. However, the relative contribution of this CCR7+ dendritic cell–mLN–Treg axis to the total intestinal Foxp3+ Treg pool during the steady-state remains unclear. In this study, the contribution of CCR7, as well as the mLN and gut-associated lymphoid tissue (GALT, to the intestinal Foxp3+ Treg compartment in the small intestine (SI and large intestine (LI was assessed. Methods: Intestinal Foxp3+ Tregs were quantitated in Ccr7-/- mice and in mice devoid of secondary lymphoid organs—including mLN and GALT—owing to a deficiency in lymphotoxin (LT signaling. Specific analyses of Foxp3+Helios+ thymically derived (tTregs and Foxp3+Helios- peripherally derived (pTregs in the SI and LI, as well as the role for the mLN in supporting Foxp3+ pTreg development using the B6.Cg-Tg(TcraTcrb425Cbn/J/ovalbumin (OVA feeding system, were performed. Results: Foxp3+ Tregs were enriched in the intestine relative to the mLN, independent of CCR7. In the absence of the mLN and GALT, normal frequency and numbers of Foxp3+ Tregs were observed in LTα-deficient (Lta-/- mice. However, Foxp3+Helios- pTregs were decreased in the SI of Lta-/- mice, corresponding with defective Foxp3+ pTreg expansion to OVA. In the LI, however, the proportion of Foxp3+Helios- pTregs and Foxp3+ pTreg induction to OVA was comparable between Lta-/- and Lta+/+ mice, which coincided with preferential expression of Treg-inducing/immunoregulatory cytokines. Conclusions: The overall size of the intestinal Foxp3+Treg pool is not impacted significantly by CCR7, mLN, or GALT during the steady-state. However, m

Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations.

Science.gov (United States)

Goudarzi, Mohammad; Tarbashevich, Katsiaryna; Mildner, Karina; Begemann, Isabell; Garcia, Jamie; Paksa, Azadeh; Reichman-Fried, Michal; Mahabaleshwar, Harsha; Blaser, Heiko; Hartwig, Johannes; Zeuschner, Dagmar; Galic, Milos; Bagnat, Michel; Betz, Timo; Raz, Erez

2017-12-04

Cell migration is essential for morphogenesis, organ formation, and homeostasis, with relevance for clinical conditions. The migration of primordial germ cells (PGCs) is a useful model for studying this process in the context of the developing embryo. Zebrafish PGC migration depends on the formation of cellular protrusions in form of blebs, a type of protrusion found in various cell types. Here we report on the mechanisms allowing the inflation of the membrane during bleb formation. We show that the rapid expansion of the protrusion depends on membrane invaginations that are localized preferentially at the cell front. The formation of these invaginations requires the function of Cdc42, and their unfolding allows bleb inflation and dynamic cell-shape changes performed by migrating cells. Inhibiting the formation and release of the invaginations strongly interfered with bleb formation, cell motility, and the ability of the cells to reach their target. Copyright © 2017 Elsevier Inc. All rights reserved.

History-dependent thermal expansion in NbO{sub 2}F

Energy Technology Data Exchange (ETDEWEB)

Wilkinson, Angus P., E-mail: angus.wilkinson@chemistry.gatech.edu [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400 (United States); School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States); Josefsberg, Ryan E.; Gallington, Leighanne C.; Morelock, Cody R.; Monaco, Christopher M. [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400 (United States)

2014-05-01

Materials with cubic ReO{sub 3}-type structures are of interest for their low or negative thermal expansion characteristics. TaO{sub 2}F is known to display almost zero thermal expansion over a wide temperature range. On heating NbO{sub 2}F, its volume coefficient of thermal expansion decreases from ∼+45 ppm K{sup −1} at 100 K to almost zero at 400 K. NbO{sub 2}F is cubic between 100 and 500 K. Samples of “NbO{sub 2}F” prepared by the digestion of Nb{sub 2}O{sub 5} in aqueous HF followed by mild drying contain hydroxyl defects and metal vacancies. On heating, they can undergo irreversible chemical changes while maintaining a cubic ReO{sub 3}-type structure. The possibility of hydroxyl defect incorporation should be considered when preparing oxyfluorides for evaluation as battery materials. - Graphical abstract: “NbO{sub 2}F” prepared by the digestion of Nb{sub 2}O{sub 5} in HF contains cation vacancies and hydroxyl groups. It undergoes irreversible changes on heating to low temperatures, unlike NbO{sub 2}F prepared by the solid state reaction of Nb{sub 2}O{sub 5} and NbF{sub 5}. - Highlights: • The digestion of Nb{sub 2}O{sub 5} in aqueous HF followed by mild drying does not produce NbO{sub 2}F. • The ReO{sub 3}-type product from the HF digestion of Nb{sub 2}O{sub 5} contains metal vacancies and hydroxyl. • The thermal expansion coefficient of NbO{sub 2}F decreases on heating and approaches zero at ∼400 K.

Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells

Science.gov (United States)

Park, Shin Yong; Gupta, Dipika; Kim, Chang H.; Dziarski, Roman

2011-01-01

Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3 −/− and Pglyrp4 −/− mice (but not Pglyrp2 −/− mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3 −/− and Pglyrp4 −/− mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3 −/− and Pglyrp4 −/− mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3 −/− mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1 −/− mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin. PMID:21949809

Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation

Directory of Open Access Journals (Sweden)

Niloufar eSafinia

2015-08-01

Full Text Available Regulatory T cells (Tregs play an important role in immunoregulation and have been shown in animal models to promote transplantation tolerance and curb autoimmunity following their adoptive transfer. The safety and potential therapeutic efficacy of these cells has already been reported in Phase I trials of bone marrow transplantation and type I diabetes, the success of which has motivated the broadened application of these cells in solid organ transplantation. Despite major advances in the clinical translation of these cells, there are still key questions to be addressed to ensure that Tregs attest their reputation as ideal candidates for tolerance induction. In this review, we will discuss the unique traits of Tregs that have attracted such fame in the arena of tolerance induction. We will outline the protocols used for their ex vivo expansion and discuss the future directions of Treg cell therapy. In this regard, we will review the concept of Treg heterogeneity, the desire to isolate and expand a functionally superior Treg population and report on the effect of differing culture conditions. The relevance of Treg migratory capacity will also be discussed together with methods of in vivo visualization of the infused cells. Moreover, we will highlight key advances in the identification and expansion of antigen specific Tregs and discuss their significance for cell therapy application. We will also summarize the clinical parameters that are of importance, alongside cell manufacture, from the choice of immunosuppression regimens to the number of injections in order to direct the success of future efficacy trials of Treg cell therapy.Years of research in the field of tolerance have seen an accumulation of knowledge and expertise in the field of Treg biology. This perpetual progression has been the driving force behind the many successes to date and has put us now within touching distance of our ultimate success, immunological tolerance.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

Science.gov (United States)

Wang, X; Qiao, Y; Yang, L; Song, S; Han, Y; Tian, Y; Ding, M; Jin, H; Shao, F; Liu, A

2017-11-01

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

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

Czech Academy of Sciences Publication Activity Database

Lukešová, E.; Bouček, J.; Rotnáglová, E.; Salaková, M.; Koslabová, E.; Grega, M.; Eckschlager, T.; Říhová, Blanka; Procházka, B.; Klozar, J.; Tachezy, R.

2014-01-01

Roč. 2, č. 303929 (2014), 1-4 ISSN 2314-6141 R&D Projects: GA MZd(CZ) NT11542 Grant - others:GA UK(CZ) SVV 266513 Institutional support: RVO:61388971 Keywords : HPV positivity * Tregs * Infection Subject RIV: EE - Microbiology, Virology

Enhanced formation and survival of CD4+ CD25hi Foxp3+ T-cells in chronic lymphocytic leukemia

NARCIS (Netherlands)

Jak, Margot; Mous, Rogier; Remmerswaal, Ester B. M.; Spijker, René; Jaspers, Annelieke; Yagüe, Adriana; Eldering, Eric; van Lier, René A. W.; van Oers, Marinus H. J.

2009-01-01

Recently, it has been described that patients with chronic lymphocytic leukemia (CLL) have increased numbers of regulatory T (T(reg)) cells. In the present study, we analysed the mechanism behind T(reg) cells expansion in CLL. Neither analysis of the T-cell receptor repertoire nor CD45 isoform

Increased frequency of CD8+ and CD4+ regulatory T cells in chronic lymphocytic leukemia: association with disease progression.

Science.gov (United States)

Jadidi-Niaragh, Farhad; Yousefi, Mehdi; Memarian, Ali; Hojjat-Farsangi, Mohammad; Khoshnoodi, Jalal; Razavi, Seyed Mohsen; Jeddi-Tehrani, Mahmood; Shokri, Fazel

2013-02-01

Little is known regarding the immunobiology of regulatory T (Treg) cells in hematopoietic malignancies, particularly in chronic lymphocytic leukemia (CLL). In the present study, we showed that the frequencies of CD8(+) and CD4(+) Treg cells were significantly increased in progressive as compared with indolent CLL patients and normal subjects. Enriched CD4(+) Treg cells induced a similar level of inhibition in polyclonally activated B cells and effector T cells from CLL patients and normal subjects. Our results suggest that the increase in circulating Treg cells may result in downregulation of tumor-specific immune response, leading to tumor expansion and disease progression.

Regulatory T Cells in Human Ovarian Cancer

Directory of Open Access Journals (Sweden)

Dong-Jun Peng

2012-01-01

Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

Science.gov (United States)

Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

2017-03-09

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

Science.gov (United States)

Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

2017-01-01

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

Subsidence transition during the post-rift stage of the Dongpu Sag, Bohai Bay Basin, NE China: A new geodynamic model

Science.gov (United States)

Xu, Han; Wang, Xin-Wen; Yan, Dan-Ping; Qiu, Liang

2018-06-01

The Dongpu Sag, located in the Bohai Bay Basin, NE China, is a Cenozoic continental rift basin. The post-rift evolution of the Dongpu Sag is associated with the development of petroleum reservoirs and has implications for Neogene-Quaternary basin evolution along the eastern margin of Eurasia. To determine the nature and origin of post-rift subsidence in the Dongpu Sag, we apply backstripping, modified strain-rate inversion, and revised finite extension modelling techniques, using data from 14 real and synthetic wells that are intersected by three seismic lines. Our results reveal discrepancies by subsidence based on backstripping of well data (the observed subsidence) minus that predicted by modified strain-rate inversion and revised finite extension modelling (the predicted subsidence). During the Miocene, the observed subsidence was smaller than the predicted subsidence, leaving negative discrepancies referred to here as "insufficient subsidence" ranging from -343 to -96 m. In contrast, during the Pliocene-Quaternary the observed subsidence was greater than the predicted subsidence by +123 to +407 m, which left positive discrepancies referred to as "over-sufficient subsidence". Therefore, we infer a transition from insufficient to over-sufficient subsidence during the post-rift stage. Normal faulting that started at ca. 5.3 Ma is estimated to have produced only ∼20% of the over-sufficient subsidence. Therefore, the remaining over-sufficient subsidence, as well as the preceding insufficient subsidence and the transition between the two, were likely controlled by lithosphere processes. We propose a new tectonic model in which variations in the conditions (e.g. rate, direction, and angle) associated with subduction of the Pacific plate resulted in a change of heat flow decreasing from a linear to a curvilinear pattern, leading to a transition from insufficient to over-sufficient subsidence.

Effects of excimer laser irradiation on the expression of Th17, Treg, TGF-beta1, and IL-6 in patients with psoriasis vulgaris

Science.gov (United States)

Xiong, Guo-Xin; Li, Xin-Zhong

2017-11-01

The effects of laser irradiation on the expression of T helper 17 (Th17) and regulatory T (Treg) cells and their related cytokines, transforming growth factor beta 1 (TGF-β1) and interleukin-6 (IL-6), respectively, in the peripheral blood of patients with psoriasis vulgaris were investigated. 38 patients with psoriasis vulgaris in the stable state were selected as the treatment group that was treated twice a week for eight weeks. Another 38 healthy persons were chosen as the control group. Before and after treatment, the percentages of Th17 cells and Treg cells in the patients’ peripheral blood were detected using flow cytometry, the content of TGF-β1 and IL-6 in the patients’ sera were detected using enzyme-linked immunosorbent assay, and the extent and severity of lesions were determined by weighing the psoriasis area and severity index (PASI). After laser treatment, the percentage of Th17 cells, the Th17/Treg cell ratio and the level of IL-6 in the peripheral blood of patients with psoriasis in the treatment group were significantly lower than those of the same patients before the treatment (P  psoriasis vulgaris was 84.21%, and the PASI score was significantly lower (P  psoriasis vulgaris.

T Helper 17 Cells Interplay with CD4+CD25highFoxp3+ Tregs in Regulation of Inflammations and Autoimmune Diseases

Science.gov (United States)

Mai, Jietang; Wang, Hong; Yang#, Xiao-Feng

2010-01-01

Interleukin-17 (IL-17)-secreting T helper 17 cells (Th17) are a recently identified CD4+ T helper subset that has been implicated in various inflammatory and autoimmune diseases. Th17, along with CD4+CD25high Foxp3+ regulatory T cells (Tregs) and other newly emergent T helper subsets, Th9 and Tfh, have expanded the Th1-Th2 paradigm. Although this newly proposed six-subset paradigm significantly improved our understanding on the differentiation of CD4+ T helper cell subsets and the regulation of T helper cells in inflammation and autoimmunity, many questions remain to be answered. In this overview, we will briefly review the following issues: a) Old Th1-Th2 paradigm versus new multi-subset paradigm; b) Structural features of IL-17 family cytokines; c) Th17 cells; d) Effects of IL-17 on various cell types and tissues; e) IL-17 receptor and signaling pathways; f) Th17-mediated inflammations; and g) Protective mechanisms of IL-17 in infections. Lastly, we will look into the interaction of Th17 and Treg in autoimmune diseases and inflammation: Th17 cells interplay with Tregs. Regulation of autoimmunity and inflammation lies in the interplays of the different T helper subsets, therefore, better understanding of these subsets’ interactions with one another would greatly improve our approaches in developing therapy to combat inflammatory and autoimmune diseases. PMID:20515737

Diagnostic value of a Rec-ELISA using Toxoplasma gondii recombinant SporoSAG, BAG1, and GRA1 proteins in murine models infected orally with tissue cysts and oocysts.

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Mert Döşkaya

Full Text Available Toxoplasma gondii causes congenital toxoplasmosis in newborns resulting with fetal anomalies. Determining the initiation time of infection is very important for pregnant women and current serological assays have drawbacks in distinguishing the recently acute toxoplasmosis. Diagnosis of recently acute infection may be improved by using stage specific antigens in serological assays. In the present study, the diagnostic value of sporozoite specific SporoSAG, bradyzoite specific BAG1 proteins and GRA1 protein expressed by all forms of the parasite have been evaluated ELISA using sera systematically collected from mice administered orally with tissue cyst and oocysts. The anti-SporoSAG IgM antibodies in sera obtained from mice infected with oocysts peaked significantly at days 1, 10, and 15 (P<0.01. The anti-BAG1 IgM antibodies in sera obtained from mice infected with tissue cysts peaked significantly at days 15, 40, and 120 (P<0.05. The anti-GRA1 IgM antibodies in sera obtained from mice infected with oocysts peaked significantly at days 2, 10, and 40 (P<0.01. The anti-GRA1 IgM antibodies in sera obtained from mice infected with tissue cysts peaked significantly only at day 40 (P<0.05. The anti-SporoSAG, anti-BAG1, and anti-GRA1 IgG titers of mice showed significant increases at day 40 (P<0.05 and decrement started for only anti-GRA1 IgG at day 120. The presence of anti-SporoSAG IgM and IgG antibodies can be interpreted as recently acute infection between days 10-40 because IgM decreases at day 40. Similarly, presence of anti-BAG1 IgM and absence of IgG can be evaluated as a recently acute infection that occurred 40 days before because IgG peaks at day 40. A peak in anti-GRA1 antibody level at first testing and reduction in consecutive sample can be considered as an infection approximately around day 40 or prior. Overall, recombinant SporoSAG, BAG1 and GRA1 proteins can be accepted as valuable diagnostic markers of recently acute toxoplasmosis.

Analysis of thermal expansivity of solids at extreme compression

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J. Shanker

2008-12-01

Full Text Available Thermodynamics of solids in the limit of infinite pressure formulated by Stacey reveals that the thermal expansivity (alpha of solids tends to zero at infinite pressure. The earlier models for the volume dependence of thermal expansivity do not satisfy the infinite pressure behaviour of thermal expansivity. The expressions for the volume dependence of the isothermal Anderson- Grüneisen parameter (delta T considered in the derivation of earlier formulations for alpha (V have been found to be inadequate. A formulation for the volume dependence of delta T is presented here which is similar to the model due to Burakovsky and Preston for the volume dependence of the Grüneisen parameter. The new formulation for alpha (V reveals that delta T infinity must be greater than zero for satisfying the thermodynamic result according to which alpha tends to zero at infinite pressure. It is found that our model fits well the experimental data on thermal expansivity alpha (V for hcp iron corresponding to a wide range of pressures (0-360 GPa.

Biodegradation and detoxification of melanoidin from distillery effluent using an aerobic bacterial strain SAG{sub 5} of Alcaligenes faecalis

Energy Technology Data Exchange (ETDEWEB)

Santal, Anita Rani, E-mail: anita.gangotra@gmail.com [Department of Microbiology, Maharshi Dayanand University, Rohtak-124001, Haryana (India); Singh, N.P. [Centre for Biotechnology, Maharshi Dayanand University, Rohtak-124001, Haryana (India); Saharan, Baljeet Singh [Department of Microbiology, Kurukshetra University, Kurukshetra-136119, Haryana (India)

2011-10-15

Highlights: {yields} The Alcaligenes faecalis strain SAG{sub 5} decolorizes 72.6 {+-} 0.56% of melanoidins. {yields} The decolorization was achieved at pH 7.5 and temperature 37 {sup o}C on 5th day. {yields} The distillery effluent after biological treatment is environmentally safe. - Abstract: Distillery effluent retains very dark brown color even after anaerobic treatment due to presence of various water soluble, recalcitrant and coloring compounds mainly melanoidins. In laboratory conditions, melanoidin decolorizing bacteria was isolated and optimized the cultural conditions at various incubation temperatures, pH, carbon sources, nitrogen sources and combined effect of both carbon and nitrogen sources. The optimum decolorization (72.6 {+-} 0.56%) of melanoidins was achieved at pH 7.5 and temperature 37 {sup o}C on 5th day of cultivation. The toxicity evaluation with mung bean (Vigna radiata) revealed that the raw distillery effluent was environmentally highly toxic as compared to biologically treated distillery effluent, which indicated that the effluent after bacterial treatment is environmentally safe. This proves to be novel biological treatment technique for biodegradation and detoxification of melanoidin from distillery effluent using the bacterial strain SAG{sub 5}.

A pre-Paleogene unconformity surface of the Sikeshu Sag, Junggar Basin: Lithological, geophysical and geochemical implications for the transportation of hydrocarbons

Directory of Open Access Journals (Sweden)

Xiaoyue Gao

2013-11-01

Full Text Available The unconformity surface at the bottom of the Paleogene is one of the most important migration pathways in the Sikeshu Sag of the Junggar Basin, which consists of three layers: upper coarse clastic rock, lower weathering crust and leached zone. The upper coarse clastic rock is characterized by higher density and lower SDT and gamma-ray logging parameters, while the lower weathering crust displays opposite features. The transport coefficient of the unconformity surface is controlled by its position in respect to the basal sandstone; it is higher in the ramp region but lower in the adjacent uplifted and sag areas. The content of saturated hydrocarbons increases with the decrease of the content of non-hydrocarbons and asphaltenes. The content of benzo[c] carbazole decreases as the content of benzo[a] carbazole and [alkyl carbazole]/[alkyl + benzo carbazole] increases. This suggests that the unconformity surface is an efficient medium for the transportation of hydrocarbons.

The impacts of voltage sags in industrial electric systems; Os impactos dos afundamentos de tensao em sistemas eletricos industriais

Energy Technology Data Exchange (ETDEWEB)

Maia, Reinaldo Moreira [Moinhos Vera Cruz, Santa Luzia, MG (Brazil); Silva, Selenio Rocha [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2010-10-15

The sensitiveness increasing of industrial equipment related to the perturbation of electric grid, resulting in losses to the productive chain, turns the energy quality in the subject more discussed by the electrical community. In this study case on the problems caused by voltage sags to equipment of an industrial plant from the food sector, it is presented the identification process and the adopted solutions. (author)

Hydrocarbon potential of a new Jurassic play, central Tunisia

International Nuclear Information System (INIS)

Beall, A.O.; Law, C.W.

1996-01-01

A largely unrecognized Jurassic Sag Basin has been identified in central Tunisia, proximal to the Permo-Carboniferous flexure delineating the northern boundary of the Saharan platform of north Africa. The northwestern margin of the Sag is delineated by an extensive region of salt-cored anticlines and localized salt diapirs extending north and west. Due to lack of deep drilling, delineation of the Sag is largely based on regional gravity data. Subsidence of the Jurassic Sag Basin is characterized by rapid expansion of Jurassic sediments from 400 m. of tidal flat and shelf carbonate at the western outcrop to over 2000 meters of tidal flat and basinal carbonate and shale within the basin center, a five-fold expansion. Rapid loading of the basin continued into Lower Cretaceous time, marked by lateral flowage of Triassic salt into pronounced structural trends. Published source rock data and interpreted subsurface well data provided the basis for GENEX 1-D hydrocarbon generation and expulsion modeling of the Sag. Middle Jurassic black source shales typically contain Type II and Type III kerogens with T.O.C.'s ranging up to 4 percent. Modeling results indicate that middle Jurassic shales are presently mature for liquid generation within portions of the Sag, with maximum generation taking place during the Tertiary. Potential hydrocarbon generation yields, based on 60 meters of mature source shale, are 20,000 BOE/acre for gas and 75,000 BOE/acre for liquids. Prospects within the region could contain an estimated potential reserve of several T.C.F. or over 1 billion barrels of oil

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Science.gov (United States)

Min, Yuanzeng; Roche, Kyle C.; Tian, Shaomin; Eblan, Michael J.; McKinnon, Karen P.; Caster, Joseph M.; Chai, Shengjie; Herring, Laura E.; Zhang, Longzhen; Zhang, Tian; Desimone, Joseph M.; Tepper, Joel E.; Vincent, Benjamin G.; Serody, Jonathan S.; Wang, Andrew Z.

2017-09-01

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

Adaptive Laguerre-Gaussian variant of the Gaussian beam expansion method.

Science.gov (United States)

Cagniot, Emmanuel; Fromager, Michael; Ait-Ameur, Kamel

2009-11-01

A variant of the Gaussian beam expansion method consists in expanding the Bessel function J0 appearing in the Fresnel-Kirchhoff integral into a finite sum of complex Gaussian functions to derive an analytical expression for a Laguerre-Gaussian beam diffracted through a hard-edge aperture. However, the validity range of the approximation depends on the number of expansion coefficients that are obtained by optimization-computation directly. We propose another solution consisting in expanding J0 onto a set of collimated Laguerre-Gaussian functions whose waist depends on their number and then, depending on its argument, predicting the suitable number of expansion functions to calculate the integral recursively.

STABILIZATION OF EXPANSIVE SOIL USING BAGASSE ASH & LIME

African Journals Online (AJOL)

tekimerry

expansive soils which depends on the stress and ... been employed to curb or reduce the severity of the damages caused by ... work is collected from Addis Ababa, Bole Sub. City at 8º 59' ..... Construction of flexible Pavements in Expansive ...

The effect of tectonic evolution on lacustrine syn-rift sediment patters in Qikou Sag, Bohaiwan Basin, eastern China

Science.gov (United States)

Liao, Y.; Wang, H.; Xu, W.

2013-12-01

Normal fault arrays and associated relay ramps between two overlapping en-echelon normal faults are well known to control the deposition and distribution of sediments in alluvial, fluvial and deltaic systems in rift settings. The influence of transfer zones or relay ramps on sediment routes and dispersal patterns in subaqueous (deeper marine/lacustrine), however, is barely studied and hence less clear. Previous experimental studies indicate that subaqueous relay ramps may act as sediment transportation pathways if certain conditions are available. In this study, we integrate detailed structural and stratigraphic analysis with three-dimensional seismic data and limited well log data from the Qikou Sag to examine the tectonic evolution and the syn-rift sediment patterns response to fault growth and linkage in an active rift setting. Qikou Sag is located at the center of Huanghua Depression, Bohaiwan Basin of eastern China. Structurally, it is a typical continental rift basin characterized by a linked system of two NEE-SWW-striking half-grabens and one E-W-striking graben. Qikou sag is filled with Eocene-Oligocene syn-rift sediments and Miocene to Quaternary post-rift sediments. The Eocene-Oligocene rifting stage can be divided into early rifting period (43-36.5 Ma, the third member and second member of Shahejie Formation, Es3 and Es2), stable rifting period (36.5-29Ma, the first member of Shaehejie Formation, Es1) and fault-depressed diversionary period (29-24.6Ma, the Dongying Formation, Ed). This study focus on the early syn-rift, the third and second member of Shehejie Formation, which is mostly dark-grey mudstone interbedded with fine to coarse-grained sandstone deposited by large-scale turbidity currents in deep-lake. In particular, we use a combination of thickness variability and facies distributions, onlap patterns within a high-resolution sequence stratigraphic framework, integrated with structural geometry, fault activity and subsidence history analysis to

Thermal expansion of fibre-reinforced composites

International Nuclear Information System (INIS)

Schneider, B.

1991-07-01

The integral thermal expansion and the coefficient of thermal expansion (CTE) of carbon and Kevlar fibre-reinforced composites were measured with high accuracy from 5 K to room temperature. For this, a laser dilatometer and a sophisticated measuring procedure were used. CTE dependence on the orientation angle ω of angle-ply laminates was determined for samples with 5 different fibre alignments (UD 0deg, +/-30deg, +/-45deg, +/-60deg and UD 90deg). A high variability of the CTE with the orientation angle was shown. At angles of approximately +/-30deg even negative CTEs were found. With suitable reinforcing fibres being selected, their absolute values rose up to 30-100% of the positive CTEs of metals. Hence, composites of this type would be suitable as compensating materials in metal constructions where little thermal expansion is desired. To check the lamination theory, theoretical computations of the CTE- ω -dependence were compared with the measured values. An excellent agreement was found. Using the lamination theory, predictions about the expansion behaviour of angle-ply laminates can be made now, if the thermal and mechanical properties of the unidirectional (UD) laminate are known. Furthermore, it is possible to carry out simulation computations aimed at investigating the influence of a single parameter of the UD-laminate (e.g. shear modulus) on the expansion of the angle-ply laminate. (orig.) [de

Saddlepoint expansions for sums of Markov dependent variables on a continuous state space

DEFF Research Database (Denmark)

Jensen, J.L.

1991-01-01

Based on the conjugate kernel studied in Iscoe et al. (1985) we derive saddlepoint expansions for either the density or distribution function of a sum f(X1)+...+f(Xn), where the Xi's constitute a Markov chain. The chain is assumed to satisfy a strong recurrence condition which makes the results...... here very similar to the classical results for i.i.d. variables. In particular we establish also conditions under which the expansions hold uniformly over the range of the saddlepoint. Expansions are also derived for sums of the form f(X1, X0)+f(X2, X1)+...+f(Xn, Xn-1) although the uniformity result...

Simultaneous interferometric measurement of linear coefficient of thermal expansion and temperature-dependent refractive index coefficient of optical materials.

Science.gov (United States)

Corsetti, James A; Green, William E; Ellis, Jonathan D; Schmidt, Greg R; Moore, Duncan T

2016-10-10

Characterizing the thermal properties of optical materials is necessary for understanding how to design an optical system for changing environmental conditions. A method is presented for simultaneously measuring both the linear coefficient of thermal expansion and the temperature-dependent refractive index coefficient of a sample interferometrically in air. Both the design and fabrication of the interferometer is presented as well as a discussion of the results of measuring both a steel and a CaF2 sample.

Spatially selective depleting tumor-associated negative regulatory T-(Treg) cells with near infrared photoimmunotherapy (NIR-PIT): A new cancer immunotherapy (Conference Presentation)

Science.gov (United States)

Kobayashi, Hisataka

2017-02-01

Near infrared photoimmunotherapy (NIR-PIT) is a new type of molecularly-targeted photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (MAb) targeting target-specific cell-surface molecules. When exposed to NIR light, the conjugate rapidly induces a highly-selective cell death only in receptor-positive, MAb-IR700-bound cells. Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting anti-tumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are well-known immune-suppressor cells that play a key role in tumor immuno-evasion and have been the target of systemic immunotherapies. We used CD25-targeted NIR-PIT to selectively deplete Tregs, thus activating CD8+ T and NK cells and restoring local anti-tumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell-line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of Tregs, thereby providing an alternative approach to cancer immunotherapy that can treat not only local tumors but also distant metastatic tumors.

Sag compensation system for assembly of MDT-chambers for the ATLAS experiment

International Nuclear Information System (INIS)

Barashkov, A.V.; Glonti, G.L.; Gongadze, A.L.; Evtukhovich, P.G.; Il'yushenko, E.N.; Kotov, S.A.; Kruchonok, V.G.; Tskhadadze, Eh.G.; Chepurnov, V.F.; Shelkov, G.A.

2005-01-01

The description of a system of the devices created for compensation of the gravitational deflection of the drift chamber during its assembly is presented. By means of this system during stage-by-stage gluing of layers of tube drift detectors to the chamber the transversal deflection considerably decreases and by that high accuracy of mutual position of separate tubes is provided. The devices were applied at assembly of 74 MDT-chambers of the ATLAS experiment. Design values of deformation of the chambers as well as the results of measurement of transversal deflections obtained during the assembly with the use of the system of sag compensation are given. Testing of chambers on the X-ray tomograph at CERN has shown that the accuracy of the positions of separate signal wires inside the assembled chambers is within the limits of the required 20 μm

Total glucosides of paeony ameliorates TNBS‑induced colitis by modulating differentiation of Th17/Treg cells and the secretion of cytokines.

Science.gov (United States)

Lin, Haihua; Zhang, Wenyou; Jiang, Xuepei; Chen, Renpin; Huang, Xielin; Huang, Zhiming

2017-12-01

The imbalance between effector CD4+ T helper 17 (Th17) and regulatory CD4+ T cells (Treg) cells and their associated cytokines, have been associated with the pathogenesis of inflammatory bowel disease (IBD). Total glycosides of paeony (TGP) is an alternative immunomodulatory agent that is widely used for the treatment of autoimmune diseases. The present study aimed to evaluate the modulatory effect of TGP in a rat model of colitis induced by 2,4,6‑trinitrobenzene sulfonic acid (TNBS). TGP was administered intragastrically 24 h after the TNBS intrarectal instillation for 7 days. TGP treatment ameliorated the clinical status and reversed the histopathologic severity of acute TNBS colitis. Furthermore, TGP inhibited the levels of Th17‑associated cytokines interleukin (IL)‑17, IL‑6, tumor necrosis factor‑α, whereas the expression levels of Treg‑associated cytokines IL‑10, transforming growth factor‑β in the plasma, colon, spleen and mesenteric lymph nodes (MLN). Additionally, TGP reduced the percentage of Th17 cells; however, the proportion of Treg cells in the spleen and MLN was increased. The present study also observed a suppression of Th17‑associated transcription factor, termed retinoid‑related orphan receptor‑γt (ROR‑γt). However, expression of the Treg‑associated transcription factor forkhead boxp3 was increased in the TGP treatment group. Therefore, the present findings suggest that TGP has a regulatory role in modulating the balance of Th17 and Treg cells to ameliorate the TNBS‑induced colitis and support the strategy of using TGP to treat IBD.

A note on asymptotic expansions for sums over a weakly dependent random field with application to the Poisson and Strauss processes

DEFF Research Database (Denmark)

Jensen, J.L.

1993-01-01

Previous results on Edgeworth expansions for sums over a random field are extended to the case where the strong mixing coefficient depends not only on the distance between two sets of random variables, but also on the size of the two sets. The results are applied to the Poisson and the Strauss...

Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients.

Science.gov (United States)

Wang, Jie; Li, Xue-Bin; Huang, Peng; Huang, Mei-Ying; Gu, Xian-Jun

2018-01-01

To investigate the changes in peripheral blood Treg/Th17 cell balance and its significance in patients with chronic renal failure (CRF) and cognitive impairment. A total of 71 patients with CRF were enrolled as a study group. The patients were divided into a cognitive impairment group and a normal cognitive function group according to the Mini-Mental State Examination (MMSE). Peripheral blood Treg and Th17 cells were analyzed by flow cytometry and their relevant cytokines (IL-17, IL-10 and TGF-β) and other biochemical indicators, including C-reactive protein (CRP) and IL-6, were determined by ELISA. Thepatients with both CRF and cognitive impairment were older than the cognitive normal groups. Peripheral blood Treg cells by Flow cytometry (the CRF cognitive impairment group 5.57±1.3%, CRF group with normal cognitive function 7.5 ± 0.9% and normal control group 9.7 ± 1.7%,Pcognitive impairment than in the group without cognitive impairment ( IL-10, 7.4±4.2 pg/mL, 13.8±3.9 pg/mL, 18.3±3.2 pg/mL; TGF-β 335.6±175.3 pg/mL, 512.7 ± 114.6 pg/mL, 953.8±373.4 pg/mL P cognitive impairment group 3.3 ± 0.7%, CRF group with normal cognitive function2.2 ± 0.5% and normal control group 1.5 ± 0.3%),and cytokine levels (IL-17, IL-6 and CRP) were higher in the group with cognitive impairment IL-6 (21.3 ± 5.1 pg/mL), IL-17 (18.5 ± 4.2 pg/mL) and CRP (20.3 ± 5.9 mg/L) in the CRF group with cognitive impairment when compared with the CRF group and normal cognitive function (12.2 ± 4.5 pg/mL, 12.1 ± 3.7 pg/mL and 13.5 ± 4.6 mg/L, respectively) or the normal control group (9.2 ± 5.8 pg/mL, 7.4 ± 2.6 pg/mL and 3.2 ± 1.3 mg/L, respectively, Pcognitive impairment in patients with CRF. © 2018 The Author(s). Published by S. Karger AG, Basel.

Anisotropic pressure dependence of Tc in single-crystal YBa2Cu3O7 via thermal expansion

International Nuclear Information System (INIS)

Meingast, C.; Blank, B.; Buerkle, H.; Obst, B.; Wolf, T.; Wuehl, H.; Selvamanickam, V.; Salama, K.

1990-01-01

High-resolution anisotropic-thermal-expansion measurements of single-crystalline and oriented-grained YBa 2 Cu 3 O 7 at the superconducting transition are presented for the first time. Discontinuities in the thermal-expansion coefficient α ab [Δα ab =(15--23)x10 -8 K -1 ], measured with a capacitance dilatometer, are found to occur in both samples. No discontinuity in α c (|Δα c | -8 K -1 ) is observed in either sample, although α c (T) shows a distinct change of slope at T c . The specific-heat discontinuity ΔC p of both samples was also measured and is used, along with the Δα's, to calculate the dependence of T c on uniaxial pressure and uniaxial strain to first order. T c is predicted to increase with pressure applied perpendicular to the c axis (dT c /dp ab =0.04--0.09 K/kbar) and to be insensitive to pressure parallel to the c axis. Uniaxial strain, on the other hand, is found to increase T c about equally in both directions

Mechanism of actuation in conducting polymers: Osmotic expansion

DEFF Research Database (Denmark)

Bay, Lasse; Jacobsen, Torben; West, Keld

2001-01-01

Conducting polymers expand or contract when their redox state is changed. This expansion/contraction effect can be separated in an intrinsic part because of changes of the polymer backbone on reduction/oxidation and a part depending on the surrounding electrolyte phase, because of osmotic expansion...... is compared with measurements on PPy(DBS) films. The experiments show that the expansion decreases as the electrolyte concentration is increased. This means that a considerable part of the total expansion is due to the osmotic effect. The osmotic effect should be taken into account when interpreting...

Temperature and orientation dependence of the short-term strength characteristics, Young's modulus, and linear expansion coefficient of ZhS6F alloy single crystals

Energy Technology Data Exchange (ETDEWEB)

Svetlov, I L; Sukhanov, N N; Krivko, A I; Roshchina, I N; Khatsinskaia, I M

1987-01-01

Experimental data are presented on the temperature dependence of the short- term strength characteristics, Young's modulus, and linear expansion coefficients of single crystals of a nickel alloy, ZhS6F, with crystallographic orientations along the 001, 111, 011, and 112 lines. It is found that the mechanical properties and Young's modulus of the alloy crystals exibit anisotropy in the temperature range 20-900 C. The linear thermal expansion coefficient is isotropic up to 900 C and equal to that of the equiaxed alloy. 10 references.

Fibroblast Growth Factor signaling regulates the expansion of A6-expressing hepatocytes in association with AKT-dependent β-catenin activation

Science.gov (United States)

Utley, Sarah; James, David; Mavila, Nirmala; Nguyen, Marie V.; Vendryes, Christopher; Salisbury, S. Michael; Phan, Jennifer; Wang, Kasper S.

2014-01-01

Background & Aims Fibroblast Growth Factors (FGFs) promote the proliferation and survival of hepatic progenitor cells (HPCs) via AKT-dependent β-catenin activation. Moreover, the emergence of hepatocytes expressing the HPC marker A6 during 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury is mediated partly by FGF and β-catenin signaling. Herein, we investigate the role of FGF signaling and AKT-mediated β-catenin activation in acute DDC liver injury. Methods Transgenic mice were fed DDC chow for 14 days concurrent with either Fgf10 over-expression or inhibition of FGF signaling via expression of soluble dominant-negative FGF Receptor (R)-2IIIb. Results After 14 days of DDC treatment, there was an increase in periportal cells expressing FGFR1, FGFR2, and AKT-activated phospho-Serine 552 (pSer552) β-CATENIN in association with up-regulation of genes encoding FGFR2IIIb ligands, Fgf7, Fgf10, and Fgf22. In response to Fgf10 over-expression, there was an increase in the number of pSer552-β-CATENIN(positive)+ive periportal cells as well as cells co-positive for A6 and hepatocyte marker, Hepatocyte Nuclear Factor-4α (HNF4α). A similar expansion of A6+ive cells was observed after Fgf10 over-expression with regular chow and after partial hepatectomy during ethanol toxicity. Inhibition of FGF signaling increased the periportal A6+iveHNF4α+ive cell population while reducing centrolobular A6+ive HNF4α+ive cells. AKT inhibition with Wortmannin attenuated FGF10-mediated A6+iveHNF4α+ive cell expansion. In vitro analyses using FGF10 treated HepG2 cells demonstrated AKT-mediated β-CATENIN activation but not enhanced cell migration. Conclusion During acute DDC treatment, FGF signaling promotes the expansion of A6-expressing liver cells partly via AKT-dependent activation of β-CATENIN expansion of A6+ive periportal cells and possibly by reprogramming of centrolobular hepatocytes. PMID:24365171

A new analysis of Mars "Special Regions": findings of the second MEPAG Special Regions Science Analysis Group (SR-SAG2).

Science.gov (United States)

Rummel, John D; Beaty, David W; Jones, Melissa A; Bakermans, Corien; Barlow, Nadine G; Boston, Penelope J; Chevrier, Vincent F; Clark, Benton C; de Vera, Jean-Pierre P; Gough, Raina V; Hallsworth, John E; Head, James W; Hipkin, Victoria J; Kieft, Thomas L; McEwen, Alfred S; Mellon, Michael T; Mikucki, Jill A; Nicholson, Wayne L; Omelon, Christopher R; Peterson, Ronald; Roden, Eric E; Sherwood Lollar, Barbara; Tanaka, Kenneth L; Viola, Donna; Wray, James J

2014-11-01

A committee of the Mars Exploration Program Analysis Group (MEPAG) has reviewed and updated the description of Special Regions on Mars as places where terrestrial organisms might replicate (per the COSPAR Planetary Protection Policy). This review and update was conducted by an international team (SR-SAG2) drawn from both the biological science and Mars exploration communities, focused on understanding when and where Special Regions could occur. The study applied recently available data about martian environments and about terrestrial organisms, building on a previous analysis of Mars Special Regions (2006) undertaken by a similar team. Since then, a new body of highly relevant information has been generated from the Mars Reconnaissance Orbiter (launched in 2005) and Phoenix (2007) and data from Mars Express and the twin Mars Exploration Rovers (all 2003). Results have also been gleaned from the Mars Science Laboratory (launched in 2011). In addition to Mars data, there is a considerable body of new data regarding the known environmental limits to life on Earth-including the potential for terrestrial microbial life to survive and replicate under martian environmental conditions. The SR-SAG2 analysis has included an examination of new Mars models relevant to natural environmental variation in water activity and temperature; a review and reconsideration of the current parameters used to define Special Regions; and updated maps and descriptions of the martian environments recommended for treatment as "Uncertain" or "Special" as natural features or those potentially formed by the influence of future landed spacecraft. Significant changes in our knowledge of the capabilities of terrestrial organisms and the existence of possibly habitable martian environments have led to a new appreciation of where Mars Special Regions may be identified and protected. The SR-SAG also considered the impact of Special Regions on potential future human missions to Mars, both as locations of

Expansions for model-independent analyses of inelastic electron scattering

International Nuclear Information System (INIS)

Jackson, D.F.; Hilton, J.M.; Roberts, A.C.M.

1977-01-01

It is noted that the commonly-used Fourier-Bessel expansion for the transition density for inelastic electron scattering depends sensitively on an arbitrary parameter and is not realistic at large distances. Alternative expansions are suggested. (author)

3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation

OpenAIRE

Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

2017-01-01

Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all i...

Effect of statins as modulators of CD39+ tregs in patients with rheumatoid arthritis who were unsuccessfully treated with methotrexate

Directory of Open Access Journals (Sweden)

Mohammed H Abu-Zaid

2018-01-01

Conclusion Combination therapy with AV and ETA provides an added immunomodulatory benefit through enhancement of the immune suppression mediated by CD39+ Treg cells. Therefore, statins can be used safely with antitumor necrosis factor drugs to control disease activity and atherosclerotic changes in patients with RA, who are treated unsuccessfully with MTX.

Distributed Low Voltage Ride-Through Operation of Power Converters in Grid-Connected Microgrids under Voltage Sags

DEFF Research Database (Denmark)

Zhao, Xin; Meng, Lexuan; Dragicevic, Tomislav

2015-01-01

it can make the MG a contributor in smooth ride through the faults. In this paper, a reactive power support strategy using droop controlled converters is proposed to aid MG riding through three phase symmetrical voltage sags. In such a case, the MGs should inject reactive power to the grid to boost...... the voltage in all phases at AC common bus. However, since the line admittances from each converter to point of common coupling (PCC) are not identical, the injected reactive power may not be equally shared. In order to achieve low voltage ride through (LVRT) capability along with a good power sharing...

Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

International Nuclear Information System (INIS)

Bilic Zabric, T.; Basic, I.

2005-01-01

Replacement of old SG (Steam Generators) [7] and the characteristic of new ones throws the question of proper accident management strategy, which leans on philosophy that repair and recovery actions have first priority. In the current NPP Krsko SAMGs (Severe Accident Management Guidelines), water supply to the SG has priority over re-injection water into the core. NPP Krsko reconsidered the highest priority of SAG-1 (inject water to the SG), against the WOG (Westinghouse Owners Group) generic approach (inject water into the core) and potential revision of Severe Accident Phenomenology Evaluations using MAAP (Modular accident Analysis Program) 4.0.5 code. (author)

Bio indication of water quality in the Bogota Sabane using fuzzy logic sagging and aquatic micro invertebrates

International Nuclear Information System (INIS)

Gutierrez, Juan David; Riss Wolfgang; Ospina Rodolfo

2002-01-01

An application of the Sagging-type fuzzy logic to calculate biological water quality in Bogota, Colombia is presented 28 sites corresponding to 9 watersheds in the Bogota area were used. The organisms selected were: Leptoceridae and Hidrobiosidae as indicators of clean waters, Planariidae and Amphipoda as indicators of polluted waters and Psychodida and Syrphidae as indicators of highly polluted waters Chironomids were also included. In order to prove the degree of reliability of Sugeno-type fuzzy logic, the results obtained were compared with values for the Cfq index, and a highly significant correlation was obtained

Cosmic growth history and expansion history

International Nuclear Information System (INIS)

Linder, Eric V.

2005-01-01

The cosmic expansion history tests the dynamics of the global evolution of the universe and its energy density contents, while the cosmic growth history tests the evolution of the inhomogeneous part of the energy density. Precision comparison of the two histories can distinguish the nature of the physics responsible for the accelerating cosmic expansion: an additional smooth component--dark energy--or a modification of the gravitational field equations. With the aid of a new fitting formula for linear perturbation growth accurate to 0.05%-0.2%, we separate out the growth dependence on the expansion history and introduce a new growth index parameter γ that quantifies the gravitational modification

Mitigation of voltage sag, swell and power factor correction using solid-state transformer b

Directory of Open Access Journals (Sweden)

M.R. Banaei

2014-09-01

Full Text Available This paper presents a novel topology of solid-state transformer (SST. In the design process, the AC/DC, DC/AC and AC/AC converters have been integrated to achieve higher efficiency. To obtain higher efficiency from other SST with DC-link topologies, the AC/DC and DC/AC converters have been integrated in one matrix converter. The proposed SST performs typical functions and has advantages such as power factor correction, voltage sag and swell elimination, voltage flicker reduction and protection capability in fault situations. In addition, it has other benefits such as light weight, low volume and elimination of hazardous liquid dielectrics because it uses medium frequency transformer. The operation and some performances of the proposed SST have been verified by the simulation results.

Suitability of human mesenchymal stem cells for gene therapy depends on the expansion medium

International Nuclear Information System (INIS)

Apel, Anja; Groth, Ariane; Schlesinger, Sabine; Bruns, Helge; Schemmer, Peter; Buechler, Markus W.; Herr, Ingrid

2009-01-01

Great hope is set in the use of mesenchymal stem cells for gene therapy and regenerative medicine. Since the frequency of this subpopulation of stem cells in bone marrow is low, mesenchymal stem cells are expanded ex vivo and manipulated prior to experimental or clinical use. Different methods for isolation and expansion are available, but the particular effect on the stem cell character is unclear. While the isolation of mesenchymal stem cells by density centrifugation followed by selection of the plastic adherent fraction is frequently used, the composition of expansion media differs. Thus, in the present study we cultured mesenchymal stem cells isolated from five healthy young volunteers in three widely used expansion media and performed a detailed analysis of the effect on morphology, proliferation, clonogenicity, passaging, differentiation and senescence. By this way we clearly show that the type of expansion medium used determines the stem cell character and time of senescence which is critical for future gene therapeutic and regenerative approaches using mesenchymal stem cells

Preliminary thermal expansion screening data for tuffs

International Nuclear Information System (INIS)

Lappin, A.R.

1980-03-01

A major variable in evaluating the potential of silicic tuffs for use in geologic disposal of heat-producing nuclear wastes is thermal expansion. Results of ambient-pressure linear expansion measurements on a group of tuffs that vary treatly in porosity and mineralogy are presente here. Thermal expansion of devitrified welded tuffs is generally linear with increasing temperature and independent of both porosity and heating rate. Mineralogic factors affecting behavior of these tuffs are limited to the presence or absence of cristobalite and altered biotite. The presence of cristobalite results in markedly nonlinear expansion above 200 0 C. If biotite in biotite-hearing rocks alters even slightly to expandable clays, the behavior of these tuffs near the boiling point of water can be dominated by contraction of the expandable phase. Expansion of both high- and low-porosity tuffs containing hydrated silicic glass and/or expandable clays is complex. The behavior of these rocks appears to be completely dominated by dehydration of hydrous phases and, hence, should be critically dependent on fluid pressure. Valid extrapolation of the ambient-pressure results presented here to depths of interest for construction of a nuclear-waste repository will depend on a good understanding of the interaction of dehydration rates and fluid pressures, and of the effects of both micro- and macrofractures on the response of tuff masss

Two-Body Orbit Expansion Due to Time-Dependent Relative Acceleration Rate of the Cosmological Scale Factor

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Lorenzo Iorio

2014-01-01

Full Text Available By phenomenologically assuming a slow temporal variation of the percent acceleration rate S̈S -1 of the cosmic scale factor S(t, it is shown that the orbit of a local binary undergoes a secular expansion. To first order in the power expansion of S̈S -1 around the present epoch t0, a non-vanishing shift per orbit (Δr of the two-body relative distance r occurs for eccentric trajectories. A general relativistic expression, which turns out to be cubic in the Hubble parameter H0 at the present epoch, is explicitly calculated for it in the case of matter-dominated epochs with Dark Energy. For a highly eccentric Oort comet orbit with period Pb ≈ 31 Myr, the general relativistic distance shift per orbit turns out to be of the order of (Δr ≈ 70 km. For the Large Magellanic Cloud, assumed on a bound elliptic orbit around the Milky Way, the shift per orbit is of the order of (Δr ≈ 2–4 pc. Our result has a general validity since it holds in any cosmological model admitting the Hubble law and a slowly varying S̈S-1(t. More generally, it is valid for an arbitrary Hooke-like extra-acceleration whose “elastic” parameter κ is slowly time-dependent, irrespectively of the physical mechanism which may lead to it. The coefficient κ1 of the first-order term of the power expansion of κ(t can be preliminarily constrained in a model-independent way down to a κ1 ≲ 2 x 10-13 year-3 level from latest Solar System’s planetary observations. The radial velocities of the double lined spectroscopic binary ALPHA Cen AB yield κ1 ≲ 10-8 year-3.

Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs.

Science.gov (United States)

Chen, Longwang; Lu, Yang; Zhao, Linjun; Hu, Lili; Qiu, Qiaomeng; Zhang, Zhuoling; Li, Mengfang; Hong, Guangliang; Wu, Bing; Zhao, Guangju; Lu, Zhongqiu

2018-05-17

Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. Copyright © 2018 Elsevier B.V. All rights reserved.

Mesozoic to Cenozoic tectonic transition process in Zhanhua Sag, Bohai Bay Basin, East China

Science.gov (United States)

Cheng, Yanjun; Wu, Zhiping; Lu, Shunan; Li, Xu; Lin, Chengyan; Huang, Zheng; Su, Wen; Jiang, Chao; Wang, Shouye

2018-04-01

The Zhanhua sag is part of the Bohai Bay intracontinental basin system that has developed since the Mesozoic in East China. The timing of this basin system coincides with the final assembly of East Asia and the development of Western Pacific-type plate margin. Here we use 3-D seismic and core log data to investigate the evolution of this basin and discuss its broad tectonic settings. Our new structural study of Zhanhua sag suggests that there are four major tectonic transitions occurred in the Bohai Bay Basin during Mesozoic and Cenozoic: (1) The first tectonic transition was from stable Craton to thrusting during the Triassic, mainly caused by the South China Block's subduction northward beneath the North China Block, which induced the formation of the NW-striking thrust faults. (2) The second tectonic transition was mainly characterized by a change from compression to extension, which can be further divided into two-stages. At the first stage, two episodes of NW-SE shortening occurred in East Asia during Early-Middle Jurassic and Late Jurassic-earliest Cretaceous, respectively. At the second stage, the extension and left-lateral shearing took place during Early Cretaceous while compression occurred during Late Cretaceous. The NW-striking thrust faults changed to normal faults and the NNE-striking left-lateral strike-slip faults started to influence the eastern part of the basin. (3) The third transition occurred when the NW-SE extension and NNE-striking right-lateral shearing started to form during Paleogene, and the peak deformation happen around 40 Ma due to the change of the subduction direction of Pacific Plate relative to Eurasia Plate. The NE-striking normal faults are the main structure, and the pre-existing NNE-striking strike-slip faults changed from left-lateral to right-lateral. (4) The fourth transition saw the regional subsidence during Neogene, which was probably caused by the India-Asia "Hard collision" between 25 and 20 Ma.

Expression of selected genes of dendritic and Treg cells in blood and skin of morphea patients treated with UVA1 phototherapy

Science.gov (United States)

Osmola-Mańkowska, Agnieszka J.; Kowalczyk, Michał J.; Żaba, Ryszard W.; Adamski, Zygmunt; Dańczak-Pazdrowska, Aleksandra

2018-01-01

Introduction Morphea is a chronic autoimmune disease characterized by fibrosis of the skin. Dendritic cells (DC) and regulatory T cells (Tregs) play a significant role in development of autoimmune and tolerance mechanisms. The aim of the study was to establish the expression of selected genes of plasmacytoid and myeloid DC, Treg cells, and the microenvironment of cytokines (interleukin-17A (IL-17A), transforming growth factor β (TGF-β)) in blood and skin of morphea patients. In addition, the effect of UVA1 phototherapy on expression of the aforementioned genes was evaluated. Material and methods The study was performed on 15 blood and 10 skin samples from patients with morphea. The evaluation included expression of CLEC4C (C-type lectin domain family 4, member C receptor), Lymphocyte antigen 75 (LY75), Forkhead box p3 (foxp3) transcription factor, IL-17A and TGF-β genes in peripheral blood mononuclear cells (PBMC) and in skin samples both before and after UVA1 phototherapy using real-time polymerase chain reaction. Results The study revealed lower expression of CLEC4C before (p = 0.010) and after (p = 0.009) phototherapy and lower expression of IL-17A before (p = 0.038) phototherapy in PBMC of patients with morphea vs. the control group. Expression of CLEC4C in PBMC correlated negatively (rho = –0.90; p = 0.001) with activity of disease after phototherapy. No significant differences were found between expression of analysed genes before and after UVA1 therapy in PBMC and skin of morphea patients. Conclusions The results do not confirm the involvement of analysed subsets of DC and Tregs in UVA1 phototherapy in morphea, but point to CLEC4C as a possible biomarker associated with the disease activity. PMID:29593811

Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency.

Directory of Open Access Journals (Sweden)

Ran Fu

Full Text Available BACKGROUND: Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA-induced asthmatic mice models. METHOD: Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. RESULTS: We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. CONCLUSION: Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells.

A pedagogical approach to the Magnus expansion

International Nuclear Information System (INIS)

Blanes, S; Casas, F; Oteo, J A; Ros, J

2010-01-01

Time-dependent perturbation theory as a tool to compute approximate solutions of the Schroedinger equation does not preserve unitarity. Here we present, in a simple way, how the Magnus expansion (also known as exponential perturbation theory) provides such unitary approximate solutions. The purpose is to illustrate the importance and consequences of such a property. We suggest that the Magnus expansion may be introduced to students in advanced courses of quantum mechanics.

Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis

DEFF Research Database (Denmark)

Pietkiewicz, H; Hiszczyńska-Sawicka, E; Kur, J

2007-01-01

The precise diagnosis of an acute and recent Toxoplasma infection in pregnant women and the newborn child is important before treatment. This study describes a new Toxoplasma gondii IgG avidity test based on a combination of recombinant GRA1, GRA7 and SAG1 antigens and shows that this test is use...

The role of fluid migration system in hydrocarbon accumulation in Maichen Sag, Beibuwan Basin

Science.gov (United States)

Liu, Hongyu; Yang, Jinxiu; Wu, Feng; Chen, Wei; Liu, Qianqian

2018-02-01

Fluid migration system is of great significance for hydrocarbon accumulation, including the primary migration and secondary migration. In this paper, the fluid migration system is analysed in Maichen Sag using seismic, well logging and core data. Results show that many factors control the hydrocarbon migration process, including hydrocarbon generation and expulsion period from source rocks, microfractures developed in the source rocks, the connected permeable sand bodies, the vertical faults cutting into/through the source rocks and related fault activity period. The spatial and temporal combination of these factors formed an effective network for hydrocarbon expulsion and accumulation, leading to the hydrocarbon reservoir distribution at present. Generally, a better understanding of the hydrocarbon migration system can explain the present status of hydrocarbon distribution, and help select future target zones for oil and gas exploration.

Voltage sag influence on fatigue life of the drivetrain of fixed speed wind turbines

DEFF Research Database (Denmark)

Veluri, Badrinath; Santos-Martin, David; Jensen, Henrik Myhre

2011-01-01

Occurrence of voltage sags due to electrical grid faults and other network disturbances generate transients of the generator electromagnetic torque which result in significant high stresses and noticeable vibrations for the wind turbine mechanical system and may also have a detrimental effect...... on the fatigue life of important drivetrain components. The high penetration of wind energy in the electrical grids demands new requirements for the operation of wind energy conversion systems. Although fixed speed wind turbine technology is nowadays replaced by variable speed wind turbines. In some countries...... by the stator flux oscillations which cause high transients of the generator electromagnetic torque. This paper focuses in estimating the resulting significant stresses transients due to the electromagnetic torque transients, which transmits to the wind turbine mechanical system that may have a detrimental...

On genus expansion of superpolynomials

Energy Technology Data Exchange (ETDEWEB)

Mironov, Andrei, E-mail: mironov@itep.ru [Lebedev Physics Institute, Moscow 119991 (Russian Federation); ITEP, Moscow 117218 (Russian Federation); National Research Nuclear University MEPhI, Moscow 115409 (Russian Federation); Morozov, Alexei, E-mail: morozov@itep.ru [ITEP, Moscow 117218 (Russian Federation); National Research Nuclear University MEPhI, Moscow 115409 (Russian Federation); Sleptsov, Alexei, E-mail: sleptsov@itep.ru [ITEP, Moscow 117218 (Russian Federation); Laboratory of Quantum Topology, Chelyabinsk State University, Chelyabinsk 454001 (Russian Federation); KdVI, University of Amsterdam (Netherlands); Smirnov, Andrey, E-mail: asmirnov@math.columbia.edu [ITEP, Moscow 117218 (Russian Federation); Columbia University, Department of Mathematics, New York (United States)

2014-12-15

Recently it was shown that the (Ooguri–Vafa) generating function of HOMFLY polynomials is the Hurwitz partition function, i.e. that the dependence of the HOMFLY polynomials on representation R is naturally captured by symmetric group characters (cut-and-join eigenvalues). The genus expansion and expansion through Vassiliev invariants explicitly demonstrate this phenomenon. In the present paper we claim that the superpolynomials are not functions of such a type: symmetric group characters do not provide an adequate linear basis for their expansions. Deformation to superpolynomials is, however, straightforward in the multiplicative basis: the Casimir operators are β-deformed to Hamiltonians of the Calogero–Moser–Sutherland system. Applying this trick to the genus and Vassiliev expansions, we observe that the deformation is fully straightforward only for the thin knots. Beyond the family of thin knots additional algebraically independent terms appear in the Vassiliev and genus expansions. This can suggest that the superpolynomials do in fact contain more information about knots than the colored HOMFLY and Kauffman polynomials. However, even for the thin knots the beta-deformation is non-innocent: already in the simplest examples it seems inconsistent with the positivity of colored superpolynomials in non-(anti)symmetric representations, which also happens in I. Cherednik's (DAHA-based) approach to the torus knots.

Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

Directory of Open Access Journals (Sweden)

Mathieu Angin

Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

Increased Tregs associated with elevated Indoleamine-2,3-dioxygenase activity and an imbalanced Kynurenine pathway in IFNpositive primary Sjögren's syndrome

NARCIS (Netherlands)

N.I. Maria (Naomi); C.G. van Helden-Meeuwsen; Z. Brkić (Zana); S.M.J. Paulissen (Sandra); E.C. Steenwijk (Eline); V.A.S.H. Dalm (Virgil); P.L.A. van Daele (Paul); M.P. van Hagen (Martin); F.G.M. Kroese (Frans G.); J.A.G. van Roon (J. A G); A. Harkin (Andrew); A.W. Dik (Willem); H.A. Drexhage (Hemmo); E.W. Lubberts (Erik); M.A. Versnel (Marjan)

2016-01-01

textabstractIntroduction Indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme converting tryptophan (TRP) to kynurenine (KYN), is driven in part by type I/II IFNs. Naïve T cells are polarized into FoxP3+ regulatory T cells (Tregs) upon exposure to either IDO+ cells or KYN. Recent studies

Anisotropic thermal expansion in flexible materials

Science.gov (United States)

Romao, Carl P.

2017-10-01

A definition of the Grüneisen parameters for anisotropic materials is derived based on the response of phonon frequencies to uniaxial stress perturbations. This Grüneisen model relates the thermal expansion in a given direction (αi i) to one element of the elastic compliance tensor, which corresponds to the Young's modulus in that direction (Yi i). The model is tested through ab initio prediction of thermal expansion in zinc, graphite, and calcite using density functional perturbation theory, indicating that it could lead to increased accuracy for structurally complex systems. The direct dependence of αi i on Yi i suggests that materials which are flexible along their principal axes but rigid in other directions will generally display both positive and negative thermal expansion.

Ferns are less dependent on passive dilution by cell expansion to coordinate leaf vein and stomatal spacing than angiosperms.

Directory of Open Access Journals (Sweden)

Madeline R Carins Murphy

Full Text Available Producing leaves with closely spaced veins is a key innovation linked to high rates of photosynthesis in angiosperms. A close geometric link between veins and stomata in angiosperms ensures that investment in enhanced venous water transport provides the strongest net carbon return to the plant. This link is underpinned by "passive dilution" via expansion of surrounding cells. However, it is not known whether this 'passive dilution' mechanism is present in plant lineages other than angiosperms and is another key feature of the angiosperms' evolutionary success. Consequently, we sought to determine whether the 'passive dilution' mechanism is; (i exclusive to the angiosperms, (ii a conserved mechanism that evolved in the common ancestor of ferns and angiosperms, or (iii has evolved continuously over time. To do this we first we assessed the plasticity of vein and stomatal density and epidermal cell size in ferns in response to light environment. We then compared the relationships between these traits found among ferns with modelled relationships that assume vein and stomatal density respond passively to epidermal cell expansion, and with those previously observed in angiosperms. Vein density, stomatal density and epidermal cell size were linked in ferns with remarkably similar relationships to those observed in angiosperms, except that fern leaves had fewer veins per stomata. However, plasticity was limited in ferns and stomatal spacing was dependent on active stomatal differentiation as well as passive cell expansion. Thus, ferns (like angiosperms appear to coordinate vein and stomatal density with epidermal cell expansion to some extent to maintain a constant ratio between veins and stomata in the leaf. The different general relationships between vein density and stomatal density in ferns and angiosperms suggests the groups have different optimum balances between the production of vein tissue dedicated to water supply and stomatal tissue for gas

Evaluation of a real-time PCR assay based on the single-copy SAG1 gene for the detection of Toxoplasma gondii.

Science.gov (United States)

Yu, Haijie; Huang, Bin; Zhuo, Xunhui; Chen, Xueqiu; Du, Aifang

2013-11-08

Real-time PCR-based detection of Toxoplasma gondii is very sensitive and convenient for diagnosing toxoplasmosis. However, the performance of the PCR assays could be influenced by the target gene chosen. Here we evaluate a real-time PCR assay using double-stranded DNA dyes (SYBR(®) Green I assay) with a new set of primers targeting the SAG1 gene for the fast and specific detection of T. gondii. The assay showed higher sensitivity than conventional PCR protocols using T. gondii DNA as template. The detection limit of the developed real-time PCR assay was in the order of 1 tachyzoite. The assay was also assessed by experimentally infected mice and showed positive results for blood (25%), spleen (50%) and lung (50%) as early as 1 dpi. The specificity of the assay was confirmed by using DNA from Neospora caninum, Escherichia coli, Babesia bovis, Trypanosoma brucei, Cryptosporidium parvum, and Toxocara canis. Assay applicability was successfully tested in blood samples collected from slaughtered pigs. These results indicate that, based on SYBR(®) green I, the quantitative SAG1 assay may also be useful in the study of the pathogenicity, immunoprophylaxis, and treatment of T. gondii. Copyright © 2013 Elsevier B.V. All rights reserved.

Investigation on the Performance of UPQC-Q for Voltage Sag Mitigation and PQ Improvement at a Critical Load Point

OpenAIRE

Basu, Malabika; Das, S. P.; Dubey, Gopal

2008-01-01

The unified power quality conditioner (UPQC) is one of the major custom power solutions, which is capable of mitigating the effect of supply voltage sag at the load end or at the point of common coupling (PCC) in a distributed network. It also prevents the propagation of the load current harmonics to the utility and improves the input power factor of the load. The control of series compensator (SERC) of the UPQC is such that it injects voltage in quadrature advance to the supply current. Thus...

Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice.

Science.gov (United States)

Liu, Xiaofei; Zhang, Juan; Zou, Qinghua; Zhong, Bing; Wang, Heng; Mou, Fangxiang; Wu, Like; Fang, Yongfei

2016-12-01

Previously, we demonstrated that Lactobacillus salivarius was more abundant in patients with rheumatoid arthritis (RA), an inflammatory autoimmune disease wherein the gut microbiota is altered, than in healthy individuals. However, the effect of L. salivarius in RA is unclear. Hence, we investigated the effect of L. salivarius isolated from patients with RA on collagen-induced arthritis (CIA) in mice. L. salivarius UCC118 or L. plantarum WCFS1 isolated from patients with RA was administered orally for 5 weeks, starting from 2 weeks before the induction of arthritis in DBA/1 mice. Clinical score progression, histological changes, serum cytokine concentrations, and the proportion of interleukin (IL)-17-producing T cells [T helper 17 (Th17)] and regulatory T cells (Tregs) in the spleen were evaluated. Bone erosion was evaluated by micro-computed tomography. CIA mice treated with either L. salivarius or L. plantarum showed lower arthritis scores, milder synovial infiltration, and less bone erosion when compared with phosphate-buffered, saline-treated CIA mice. Administration of L. salivarius and L. plantarum reduced the Th17 cell fraction and increased the Treg fraction. L. salivarius-treated CIA mice displayed a significant increase in serum anti-inflammatory IL-10 levels. Thus, pretreatment with L. salivarius could significantly improve CIA in mice and may help alleviate RA in a clinical setting.

Current source converter based D-STATCOM for voltage sag mitigation

Directory of Open Access Journals (Sweden)

Singh Moirangthem Deben

2015-01-01

Full Text Available This paper presents a novel method of realizing one of the custom power controllers, the distribution static synchronous compensator (D-STATCOM using current source converter (CSC topology. Almost all the custom power controllers such as dynamic voltage restorer (DVR, unified power quality conditioner (UPQC including D-STATCOM are generally designed and implemented by using voltage source converters (VSC and not much research publications with CSC based approach has been reported over the last one decade. Since the D-STATCOM is a current injection device, its performance can be improved when realized by a current-source converter which can generate a controllable current directly at its output terminals and offers many advantageous features. In this paper, an attempt has been made to study the performance of a CSC based D-STATCOM suitable for use in the power distribution system in order to mitigate voltage sag and improve power quality. The proposed model uses a three leg CSC whose switching strategy is based on sinusoidal pulse width modulation (SPWM. The model has been simulated in the Matlab/Simulink environment. The results of the simulation runs under steady state and dynamic load perturbation provide excellent voltage and current waveforms that support the justification of the proposed model.

Improvement of Expansive Soils Using Chemical Stabilizers

Science.gov (United States)

Ikizler, S. B.; Senol, A.; Khosrowshahi, S. K.; Hatipoğlu, M.

2014-12-01

The aim of this study is to investigate the effect of two chemical stabilizers on the swelling potential of expansive soil. A high plasticity sodium bentonite was used as the expansive soil. The additive materials including fly ash (FA) and lime (L) were evaluated as potential stabilizers to decrease the swelling pressure of bentonite. Depending on the type of additive materials, they were blended with bentonite in different percentages to assess the optimum state and approch the maximum swell pressure reduction. According to the results of swell pressure test, both fly ash and lime reduce the swelling potential of bentonite but the maximum improvement occurs using bentonite-lime mixture while the swelling pressure reduction approaches to 49%. The results reveal a significant reduction of swelling potential of expansive soil using chemical stabilizers. Keywords: Expansive soil; swell pressure; chemical stabilization; fly ash; lime

Daratumumab depletes CD38sup>+> immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma

DEFF Research Database (Denmark)

Krejcik, Jakub; Casneuf, Tineke; Nijhof, Inger S

2016-01-01

target non-plasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations. Peripheral blood (PB) and bone marrow (BM) from patients with relapsed/refractory myeloma from two daratumumab monotherapy studies were analyzed before and during therapy......Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with cross-linking. These mechanisms may also...... and at relapse. Regulatory B cells (Bregs) and myeloid-derived suppressor cells (MDSCs), previously shown to express CD38, were evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting. A novel subpopulation of regulatory T cells (Tregs) expressing CD38 was identified...

Asymptotic expansions for high-contrast elliptic equations

KAUST Repository

Calo, Victor M.; Efendiev, Yalchin R.; Galvis, Juan

2014-01-01

In this paper, we present a high-order expansion for elliptic equations in high-contrast media. The background conductivity is taken to be one and we assume the medium contains high (or low) conductivity inclusions. We derive an asymptotic expansion with respect to the contrast and provide a procedure to compute the terms in the expansion. The computation of the expansion does not depend on the contrast which is important for simulations. The latter allows avoiding increased mesh resolution around high conductivity features. This work is partly motivated by our earlier work in [Domain decomposition preconditioners for multiscale flows in high-contrast media, Multiscale Model Simul. 8 (2010) 1461-1483] where we design efficient numerical procedures for solving high-contrast problems. These multiscale approaches require local solutions and our proposed high-order expansion can be used to approximate these local solutions inexpensively. In the case of a large-number of inclusions, the proposed analysis can help to design localization techniques for computing the terms in the expansion. In the paper, we present a rigorous analysis of the proposed high-order expansion and estimate the remainder of it. We consider both high-and low-conductivity inclusions. © 2014 World Scientific Publishing Company.

Asymptotic expansions for high-contrast elliptic equations

KAUST Repository

Calo, Victor M.

2014-03-01

In this paper, we present a high-order expansion for elliptic equations in high-contrast media. The background conductivity is taken to be one and we assume the medium contains high (or low) conductivity inclusions. We derive an asymptotic expansion with respect to the contrast and provide a procedure to compute the terms in the expansion. The computation of the expansion does not depend on the contrast which is important for simulations. The latter allows avoiding increased mesh resolution around high conductivity features. This work is partly motivated by our earlier work in [Domain decomposition preconditioners for multiscale flows in high-contrast media, Multiscale Model Simul. 8 (2010) 1461-1483] where we design efficient numerical procedures for solving high-contrast problems. These multiscale approaches require local solutions and our proposed high-order expansion can be used to approximate these local solutions inexpensively. In the case of a large-number of inclusions, the proposed analysis can help to design localization techniques for computing the terms in the expansion. In the paper, we present a rigorous analysis of the proposed high-order expansion and estimate the remainder of it. We consider both high-and low-conductivity inclusions. © 2014 World Scientific Publishing Company.

Histone methylation mediates plasticity of human FOXP3(+) regulatory T cells by modulating signature gene expressions.

Science.gov (United States)

He, Haiqi; Ni, Bing; Tian, Yi; Tian, Zhiqiang; Chen, Yanke; Liu, Zhengwen; Yang, Xiaomei; Lv, Yi; Zhang, Yong

2014-03-01

CD4(+) FOXP3(+) regulatory T (Treg) cells constitute a heterogeneous and plastic T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. However, the fate of human Treg cells after loss of FOXP3 expression and the epigenetic mechanisms contributing to such a phenotype switch remain to be fully elucidated. In the current study, we demonstrate that human CD4(+) CD25(high) CD127(low/-) Treg cells convert to two subpopulations with distinctive FOXP3(+) and FOXP3(-) phenotypes following in vitro culture with anti-CD3/CD28 and interleukin-2. Digital gene expression analysis showed that upon in vitro expansion, human Treg cells down-regulated Treg cell signature genes, such as FOXP3, CTLA4, ICOS, IKZF2 and LRRC32, but up-regulated a set of T helper lineage-associated genes, especially T helper type 2 (Th2)-associated, such as GATA3, GFI1 and IL13. Subsequent chromatin immunoprecipitation-sequencing of these subpopulations yielded genome-wide maps of their H3K4me3 and H3K27me3 profiles. Surprisingly, reprogramming of Treg cells was associated with differential histone modifications, as evidenced by decreased abundance of permissive H3K4me3 within the down-regulated Treg cell signature genes, such as FOXP3, CTLA4 and LRRC32 loci, and increased abundance of H3K4me3 within the Th2-associated genes, such as IL4 and IL5; however, the H3K27me3 modification profile was not significantly different between the two subpopulations. In conclusion, this study revealed that loss of FOXP3 expression from human Treg cells during in vitro expansion can induce reprogramming to a T helper cell phenotype with a gene expression signature dominated by Th2 lineage-associated genes, and that this cell type conversion may be mediated by histone methylation events. © 2013 John Wiley & Sons Ltd.

Histone methylation mediates plasticity of human FOXP3+ regulatory T cells by modulating signature gene expressions

Science.gov (United States)

He, Haiqi; Ni, Bing; Tian, Yi; Tian, Zhiqiang; Chen, Yanke; Liu, Zhengwen; Yang, Xiaomei; Lv, Yi; Zhang, Yong

2014-01-01

CD4+ FOXP3+ regulatory T (Treg) cells constitute a heterogeneous and plastic T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. However, the fate of human Treg cells after loss of FOXP3 expression and the epigenetic mechanisms contributing to such a phenotype switch remain to be fully elucidated. In the current study, we demonstrate that human CD4+ CD25high CD127low/− Treg cells convert to two subpopulations with distinctive FOXP3+ and FOXP3− phenotypes following in vitro culture with anti-CD3/CD28 and interleukin-2. Digital gene expression analysis showed that upon in vitro expansion, human Treg cells down-regulated Treg cell signature genes, such as FOXP3, CTLA4, ICOS, IKZF2 and LRRC32, but up-regulated a set of T helper lineage-associated genes, especially T helper type 2 (Th2)-associated, such as GATA3, GFI1 and IL13. Subsequent chromatin immunoprecipitation-sequencing of these subpopulations yielded genome-wide maps of their H3K4me3 and H3K27me3 profiles. Surprisingly, reprogramming of Treg cells was associated with differential histone modifications, as evidenced by decreased abundance of permissive H3K4me3 within the down-regulated Treg cell signature genes, such as FOXP3, CTLA4 and LRRC32 loci, and increased abundance of H3K4me3 within the Th2-associated genes, such as IL4 and IL5; however, the H3K27me3 modification profile was not significantly different between the two subpopulations. In conclusion, this study revealed that loss of FOXP3 expression from human Treg cells during in vitro expansion can induce reprogramming to a T helper cell phenotype with a gene expression signature dominated by Th2 lineage-associated genes, and that this cell type conversion may be mediated by histone methylation events. PMID:24152290

TESTING THE EFFECTS OF EXPANSION ON SOLAR WIND TURBULENCE

Energy Technology Data Exchange (ETDEWEB)

Vech, Daniel; Chen, Christopher H K, E-mail: dvech@umich.edu [Department of Physics, Imperial College London, London SW7 2AZ (United Kingdom)

2016-11-20

We present a multi-spacecraft approach to test the predictions of recent studies on the effect of solar wind expansion on the radial spectral, variance, and local 3D anisotropies of the turbulence. We found that on small scales (5000–10,000 km) the power levels of the B-trace structure functions do not depend on the sampling direction with respect to the radial suggesting that on this scale the effect of expansion is small possibly due to fast turbulent timescales. On larger scales (110–135 R{sub E}), the fluctuations of the radial magnetic field component are reduced by ∼20% compared to the transverse (perpendicular to radial) ones, which could be due to expansion confining the fluctuations into the plane perpendicular to radial. For the local 3D spectral anisotropy, the B-trace structure functions showed dependence on the sampling direction with respect to radial. The anisotropy in the perpendicular plane is reduced when the increments are taken perpendicular with respect to radial, which could be an effect of expansion.

TESTING THE EFFECTS OF EXPANSION ON SOLAR WIND TURBULENCE

International Nuclear Information System (INIS)

Vech, Daniel; Chen, Christopher H K

2016-01-01

We present a multi-spacecraft approach to test the predictions of recent studies on the effect of solar wind expansion on the radial spectral, variance, and local 3D anisotropies of the turbulence. We found that on small scales (5000–10,000 km) the power levels of the B-trace structure functions do not depend on the sampling direction with respect to the radial suggesting that on this scale the effect of expansion is small possibly due to fast turbulent timescales. On larger scales (110–135 R E ), the fluctuations of the radial magnetic field component are reduced by ∼20% compared to the transverse (perpendicular to radial) ones, which could be due to expansion confining the fluctuations into the plane perpendicular to radial. For the local 3D spectral anisotropy, the B-trace structure functions showed dependence on the sampling direction with respect to radial. The anisotropy in the perpendicular plane is reduced when the increments are taken perpendicular with respect to radial, which could be an effect of expansion.

Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway.

Science.gov (United States)

Zhang, Song-An; Niyazi, Hu-Er-Xi-Dan; Hong, Wen; Tuluwengjiang, Gu-Li-Xian; Zhang, Lei; Zhang, Yang; Su, Wei-Peng; Bao, Yong-Xing

2017-03-01

This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4 + /CD8 + T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4 + T cells and CD8 + T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates

Geophysical Prediction Technology Based on Organic Carbon Content in Source Rocks of the Huizhou Sag, the South China Sea

Directory of Open Access Journals (Sweden)

Yang Wei

2017-08-01

Full Text Available Due to the high exploration cost, limited number of wells for source rocks drilling and scarce test samples for the Total Organic Carbon Content (TOC in the Huizhou sag, the TOC prediction of source rocks in this area and the assessment of resource potentials of the basin are faced with great challenges. In the study of TOC prediction, predecessors usually adopted the logging assessment method, since the data is only confined to a “point” and the regional prediction of the source bed in the seismic profile largely depends on the recognition of seismic facies, making it difficult to quantify TOC. In this study, we combined source rock geological characteristics, logging and seismic response and built the mathematical relation between quasi TOC curve and seismic data based on the TOC logging date of a single well and its internal seismic attribute. The result suggested that it was not purely a linear relationship that was adhered to by predecessors, but was shown as a complicated non-linear relationship. Therefore, the neural network algorithm and SVMs were introduced to obtain the optimum relationship between the quasi TOC curve and the seismic attribute. Then the goal of TOC prediction can be realized with the method of seismic inversion.

Temperature dependence of volume thermal expansion for NaCl and KCl crystals

International Nuclear Information System (INIS)

Fang Zhenghua

2005-01-01

A new relation for predicting volume thermal expansion of alkali halides at high temperatures is derived based on the assumption that the two different diffusional driving force models presented, respectively, by Sharma and Sharma (Indian J. Pure Appl. Phys. 29 (1991) 637) and Singh (J. Phys. Chem. Solids 63 (2002) 1935) are equivalent. The input parameters needed for the calculation are the volume thermal expansion coefficient and the isothermal Anderson-Gruneisen parameter, both at room temperature and zero pressure, which are available from the literature. The tests on NaCl and KCl crystals demonstrate that the agreement between the calculated results obtained by this relation and the corresponding experimental data is very good. The applicability of the relation as well as some thermodynamic relationships included in its derivation is discussed

(99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs.

Science.gov (United States)

Su, Dinglei; Shen, Minning; Gu, Bingjie; Wang, Xiaoqin; Wang, Dandan; Li, Xia; Sun, Lingyun

2016-06-01

γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients. To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA. Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 μg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured with enzyme-linked immunosorbent assay. After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-β. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-β and decreased disease activity. (99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-β and decreasing TNF-α and IL-6. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Physical simulation of gas reservoir formation in the Liwan 3-1 deep-water gas field in the Baiyun sag, Pearl River Mouth Basin

Directory of Open Access Journals (Sweden)

Gang Gao

2015-01-01

Full Text Available To figure out the process and controlling factors of gas reservoir formation in deep-waters, based on an analysis of geological features, source of natural gas and process of reservoir formation in the Liwan 3-1 gas field, physical simulation experiment of the gas reservoir formation process has been performed, consequently, pattern and features of gas reservoir formation in the Baiyun sag has been found out. The results of the experiment show that: ① the formation of the Liwan 3-1 faulted anticline gas field is closely related to the longstanding active large faults, where natural gas is composed of a high proportion of hydrocarbons, a small amount of non-hydrocarbons, and the wet gas generated during highly mature stage shows obvious vertical migration signs; ② liquid hydrocarbons associated with natural gas there are derived from source rock of the Enping & Zhuhai Formation, whereas natural gas comes mainly from source rock of the Enping Formation, and source rock of the Wenchang Formation made a little contribution during the early Eocene period as well; ③ although there was gas migration and accumulation, yet most of the natural gas mainly scattered and dispersed due to the stronger activity of faults in the early period; later as fault activity gradually weakened, gas started to accumulate into reservoirs in the Baiyun sag; ④ there is stronger vertical migration of oil and gas than lateral migration, and the places where fault links effective source rocks with reservoirs are most likely for gas accumulation; ⑤ effective temporal-spatial coupling of source-fault-reservoir in late stage is the key to gas reservoir formation in the Baiyun sag; ⑥ the nearer the distance from a trap to a large-scale fault and hydrocarbon source kitchen, the more likely gas may accumulate in the trap in late stage, therefore gas accumulation efficiency is much lower for the traps which are far away from large-scale faults and hydrocarbon source

Thermal expansion accompanying the glass-liquid transition and crystallization

Directory of Open Access Journals (Sweden)

M. Q. Jiang

2015-12-01

Full Text Available We report the linear thermal expansion behaviors of a Zr-based (Vitreloy 1 bulk metallic glass in its as-cast, annealed and crystallized states. Accompanying the glass-liquid transition, the as-cast Vitreloy 1 shows a continuous decrease in the thermal expansivity, whereas the annealed glass shows a sudden increase. The crystallized Vitreloy 1 exhibits an almost unchanged thermal expansivity prior to its melting. Furthermore, it is demonstrated that the nucleation of crystalline phases can induce a significant thermal shrinkage of the supercooled liquid, but with the growth of these nuclei, the thermal expansion again dominates. These results are explained in the framework of the potential energy landscape, advocating that the configurational and vibrational contributions to the thermal expansion of the glass depend on both, structure and temperature.

Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice.

Science.gov (United States)

Zheng, Lingjie; Sharma, Rahul; Kung, John T; Deshmukh, Umesh S; Jarjour, Wael N; Fu, Shu Man; Ju, Shyr-Te

2008-04-01

We hypothesize that regulatory T-cell (Treg)-deficient strains have an altered TCR repertoire in part due to the expansion of autoimmune repertoire by self-antigen. We compared the Vbeta family expression profile between B6 and Treg-lacking B6.Cg-Foxp3(sf)(/Y) (B6.sf) mice using fluorescent anti-Vbeta mAbs and observed no changes. However, while the spectratypes of 20 Vbeta families among B6 mice were highly similar, the Vbeta family spectratypes of B6.sf mice were remarkably different from B6 mice and from each other. Significant spectratype changes in many Vbeta families were also observed in Treg-deficient IL-2 knockout (KO) and IL-2Ralpha KO mice. Such changes were not observed with anti-CD3 mAb-treated B6 mice or B6 CD4+CD25- T cells. TCR transgenic (OT-II.sf) mice displayed dramatic reduction of clonotypic TCR with concomitant increase in T cells bearing non-transgenic Vbeta and Valpha families, including T cells with dual receptors expressing reduced levels of transgenic Valpha and endogenous Valpha. Collectively, the data demonstrate that Treg deficiency allows polyclonal expansion of T cells in a stochastic manner, resulting in widespread changes in the TCR repertoire.

Reconstitution of Th17, Tc17 and Treg cells after paediatric haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, Katrine; Ryder, Lars P; Lennox-Hvenekilde, David

2018-01-01

behind these associations have not been investigated previously. We hypothesized that increased levels of IL-7 post-transplant alters the balance between immune-regulatory T cell subsets during the post-transplant lymphocyte recovery towards a more pro-inflammatory profile. We quantified Th17 cells, Tc17.......025). The plasma level of IL-7 at day +90 correlated inversely with Th17 cell counts (rs=-0.65, P=0.0002) and the proportion of Tc17 cells (rs=0.64, P=0.0005) at day +90, but not with Tregs. Furthermore, high IL-7 levels at day +7 were predictive of a less naïve T-cell phenotype at day +90. These findings add...

Temperature dependence of thermal expansion of cadmium sulfide in the temperature range 20 - 820 K

International Nuclear Information System (INIS)

Oskotskij, V.S.; Kobyakov, I.B.; Solodukhin, A.V.

1980-01-01

The linear thermal expansion of cadmium sulfide is measured perpendicularly (α 1 ) and parallelly (α 2 ) to the hexagonal axis in the temperature range from 20 to 820 K. Anisotropy is low at up to 80 K; rises at higher temperatures; at 3OO K α 1 /α 3 ratio is 1.8; at 820 K, 2.4. Heat expansion is negative at temperatures lower than 104.5 K(α 1 ) and 126.0 K(α 2 ). It achieves the minimum at 43.6 K (α 1 ) and 52.5K (α 3 ). The theory of heat expansion is plotted in the Debue, approximation and cadmium sulfide is considered as an isotope crystal with average elastic constants. Two parameters of the theory are determined by the position and value of the minimum of volumetric thermal expansion of the model isotope crystal. The theoretic curve agrees well with the experimental one at temperatures up to 160 K, i.e in the range of applicability of the Debue approximation and the isotropic model

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

Science.gov (United States)

Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

2016-01-01

Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

Thermal Expansion Anomaly Regulated by Entropy

Science.gov (United States)

Liu, Zi-Kui; Wang, Yi; Shang, Shunli

2014-11-01

Thermal expansion, defined as the temperature dependence of volume under constant pressure, is a common phenomenon in nature and originates from anharmonic lattice dynamics. However, it has been poorly understood how thermal expansion can show anomalies such as colossal positive, zero, or negative thermal expansion (CPTE, ZTE, or NTE), especially in quantitative terms. Here we show that changes in configurational entropy due to metastable micro(scopic)states can lead to quantitative prediction of these anomalies. We integrate the Maxwell relation, statistic mechanics, and first-principles calculations to demonstrate that when the entropy is increased by pressure, NTE occurs such as in Invar alloy (Fe3Pt, for example), silicon, ice, and water, and when the entropy is decreased dramatically by pressure, CPTE is expected such as in anti-Invar cerium, ice and water. Our findings provide a theoretic framework to understand and predict a broad range of anomalies in nature in addition to thermal expansion, which may include gigantic electrocaloric and electromechanical responses, anomalously reduced thermal conductivity, and spin distributions.

Semiclassical expansions of the nuclear relativistic Hartree-Fock theory

International Nuclear Information System (INIS)

Weigel, M.K.; Haddad, S.

1991-01-01

Semiclassical expansions for Green functions, self-energy, phase-space density and density are given and discussed. The many-body problem was treated in the relativistic Hartree-Fock approximation with a Lagrangian with a standard OBE potential structure including the possibility of space-dependent couplings. The expansions are obtained by formulating the many-body problem in the mixed position-momentum (Wigner) representation and application of the (h/2π)-Wigner-Kirkwood expansion scheme. The resulting self-consistency problems for the zeroth and second order are formulated in three versions. (author)

A low-angle normal fault and basement structures within the Enping Sag, Pearl River Mouth Basin: Insights into late Mesozoic to early Cenozoic tectonic evolution of the South China Sea area

Science.gov (United States)

Ye, Qing; Mei, Lianfu; Shi, Hesheng; Shu, Yu; Camanni, Giovanni; Wu, Jing

2018-04-01

The basement structure of the Cenozoic Enping Sag, within the Pearl River Mouth Basin on the northern margin of South China Sea, is revealed by borehole-constrained high-quality 3D seismic reflection data. Such data suggest that the Enping Sag is bounded in the north by a low-angle normal fault. We interpret this low-angle normal fault to have developed as the result of the reactivation of a pre-existing thrust fault part of a pre-Cenozoic thrust system. This is demonstrated by the selective reactivation of the pre-existing thrust and by diffuse contractional deformation recognized from the accurate analysis of basement reflections. Another significant result of this study is the finding of some residual rift basins within the basement of the Enping Sag. Both the thrust system and the residual basins are interpreted to have developed after the emplacement of continental margin arc-related granitoids (J3-K1) that define the basement within the study area. Furthermore, seismic sections show that the pre-existing residual rift basins are offset by the main thrust fault and they are both truncated by the Tg unconformity. These structural relationships, interpreted in the frame of previous studies, help us to reconstruct a six-event structural evolution model for the Enping Sag from the late Mesozoic to the early Cenozoic. In particular, we interpret the residual rift basins to have formed as the result of back-arc extension due to the slab roll-back of the Paleo-Pacific Plate subduction in the early K2. The thrust system has recorded a compressional event in the late K2 that followed the back-arc extension in the SCS area. The mechanism of this compressional event is still to be clarified, and might be related to continuous subduction of the Paleo-Pacific Plate or to the continent-continent collision between a micro-continental block and the South China margin.

The interaction between regulatory T cells and NKT cells in the liver: a CD1d bridge links innate and adaptive immunity.

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Hua, Jing; Liang, Shuwen; Ma, Xiong; Webb, Tonya J; Potter, James P; Li, Zhiping

2011-01-01

Regulatory T cells (Tregs) and natural killer T (NKT) cells are two distinct lymphocyte subsets that independently regulate hepatic adaptive and innate immunity, respectively. In the current study, we examine the interaction between Tregs and NKT cells to understand the mechanisms of cross immune regulation by these cells. The frequency and function of Tregs were evaluated in wild type and NKT cell deficient (CD1dko) mice. In vitro lymphocyte proliferation and apoptosis assays were performed with NKT cells co-cultured with Tregs. The ability of Tregs to inhibit NKT cells in vivo was examined by adoptive transfer of Tregs in a model of NKT cell mediated hepatitis. CD1dko mice have a significant reduction in hepatic Tregs. Although, the Tregs from CD1dko mice remain functional and can suppress conventional T cells, their ability to suppress activation induced NKT cell proliferation and to promote NKT cell apoptosis is greatly diminished. These effects are CD1d dependent and require cell to cell contact. Adoptive transfer of Tregs inhibits NKT cell-mediated liver injury. NKT cells promote Tregs, and Tregs inhibit NKT cells in a CD1d dependent manner requiring cell to cell contact. These cross-talk immune regulations provide a linkage between innate and adaptive immunity.

Interplay of T Helper 17 Cells with CD4+CD25high FOXP3+ Tregs in Regulation of Allergic Asthma in Pediatric Patients

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Amit Agarwal

2014-01-01

Full Text Available Background. There is evidence that Tregs are important to prevent allergic diseases like asthma but limited literature exists on role of TH17 cells in allergic diseases. Methods. Fifty children with asthma and respiratory allergy (study group and twenty healthy children (control group were recruited in this study. Total IgE levels and pulmonary function tests were assessed. The expression of Tregs and cytokines was determined by flow cytometry. Results. The average level of total IgE in study group (316.8 ± 189.8 IU/mL was significantly higher than controls (50 ± 17.5 IU/mL, P<0.0001. The frequency of TH17 cells and culture supernatant level of IL-17 in study group (12.09 ± 8.67 pg/mL was significantly higher than control group (2.01 ± 1.27 pg/mL, P<0.001. Alternatively, the frequency of FOXP3 level was significantly lower in study group [(49.00 ± 13.47%] than in control group [(95.91 ± 2.63%] and CD4+CD25+FOXP3+ to CD4+CD25+ ratio was also significantly decreased in study group [(6.33 ± 2.18%] compared to control group [(38.61 ± 11.04%]. The total serum IgE level is negatively correlated with FOXP3 level (r=-0.5273, P<0.0001. The FOXP3 expression is negatively correlated with the IL-17 levels (r=-0.5631, P<0.0001 and IL-4 levels (r=-0.2836, P=0.0460. Conclusions. Imbalance in TH17/Tregs, elevated IL-17, and IL-4 response and downregulation of FOXP3 were associated with allergic asthma.

Linear expansion of products out of thermal splitting graphite

International Nuclear Information System (INIS)

Tishina, E.A.; Kurnevich, G.I.

1994-01-01

Linear expansion of thermally split graphite in the form of foil and pressed items of different density was studied. It is ascertained that the extreme character of temperature dependence of linear expansion factor of pressed samples of thermally split graphite is determined by the formation of closed pores containing air in the course of their production. 3 refs., 2 figs

T-Bet Enhances Regulatory T Cell Fitness and Directs Control of Th1 Responses in Crescentic GN.

Science.gov (United States)

Nosko, Anna; Kluger, Malte A; Diefenhardt, Paul; Melderis, Simon; Wegscheid, Claudia; Tiegs, Gisa; Stahl, Rolf A K; Panzer, Ulf; Steinmetz, Oliver M

2017-01-01

Th1 cells are central pathogenic mediators of crescentic GN (cGN). Mechanisms responsible for Th1 cell downregulation, however, remain widely unknown. Recently, it was proposed that activation of the Th1-characteristic transcription factor T-bet optimizes Foxp3 + regulatory T (Treg) cells to counteract Th1-type inflammation. Because very little is known about the role of T-bet + Treg1 cells in inflammatory diseases, we studied the function of these cells in the nephrotoxic nephritis (NTN) model of cGN. The percentage of Treg1 cells progressively increased in kidneys of nephritic wild-type mice during the course of NTN, indicating their functional importance. Notably, naïve Foxp3 Cre xT-bet fl/fl mice, lacking Treg1 cells, showed spontaneous skewing toward Th1 immunity. Furthermore, absence of Treg1 cells resulted in aggravated NTN with selectively dysregulated renal and systemic Th1 responses. Detailed analyses of Treg cells from Foxp3 Cre xT-bet fl/fl mice revealed unaltered cytokine production and suppressive capacity. However, in competitive cotransfer experiments, wild-type Treg cells outcompeted T-bet-deficient Treg cells in terms of population expansion and expression levels of Foxp3, indicating that T-bet expression is crucial for general Treg fitness. Additionally, T-bet-deficient Treg cells lacked expression of the Th1-characteristic trafficking receptor CXCR3, which correlated with significant impairment of renal Treg infiltration. In summary, our data indicate a new subtype of Treg cells in cGN. These Treg1 cells are characterized by activation of the transcription factor T-bet, which enhances the overall fitness of these cells and optimizes their capacity to downregulate Th1 responses by inducing chemokine receptor CXCR3 expression. Copyright © 2016 by the American Society of Nephrology.

Extension of the Accurate Voltage-Sag Fault Location Method in Electrical Power Distribution Systems

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Youssef Menchafou

2016-03-01

Full Text Available Accurate Fault location in an Electric Power Distribution System (EPDS is important in maintaining system reliability. Several methods have been proposed in the past. However, the performances of these methods either show to be inefficient or are a function of the fault type (Fault Classification, because they require the use of an appropriate algorithm for each fault type. In contrast to traditional approaches, an accurate impedance-based Fault Location (FL method is presented in this paper. It is based on the voltage-sag calculation between two measurement points chosen carefully from the available strategic measurement points of the line, network topology and current measurements at substation. The effectiveness and the accuracy of the proposed technique are demonstrated for different fault types using a radial power flow system. The test results are achieved from the numerical simulation using the data of a distribution line recognized in the literature.

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

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Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

2012-05-10

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

Angular dependence of resonant inelastic x-ray scattering : A spherical tensor expansion

NARCIS (Netherlands)

Juhin, Amelie; Brouder, Christian; de Groot, Frank

A spherical tensor expansion is carried out to express the resonant inelastic scattering cross-section as a sum of products of fundamental spectra with tensors involving wavevectors and polarization vectors of incident and scattered photons. The expression presented in this paper differs from that

Regulatory T cells participation in the infection immunopathogenesis by the Human Immunodeficiency Virus (HIV-1 Participação de células T regulatórias (Tregs na imunopatogênese da infecção pelo vírus da imunodeficiência humana 1 (HIV-1

Directory of Open Access Journals (Sweden)

Isabele Kazahaya Borges

2010-12-01

Full Text Available The survival of patients infected with human immunodeficiency virus (HIV-1 is related to the prevention and effective treatment of opportunistic infections. It is known that the main parameters to evaluate the progression of disease caused by HIV-1 is the counting of CD4 + T cells and viral load of HIV-1. Regulatory T cells has been considered the focus of intense research within the immune system as well as in the pathogenesis of several diseases. Natural regulatory T cells (Tregs CD4+CD25+ act in the modulation of immune activation, functioning as critical mediators of immune homeostasis and self-tolerance. Furthermore, recent studies has shown that the function of Tregs cells is not limited to the prevention of autoimmunity, but is also important to control all forms of immune responses in the context of inflammation, infection, allergy, transplantation and tumor immunity. Many authors have identified Tregs as beneficial effector cells in the context of AIDS, but other researchers disagree. Tregs can exert an important role in the immunopathology of HIV infection due to the suppressor activity on cellular activation and effector function. Thus, this review discusses the molecular and immunological aspects of Tregs in the HIV system. A sobrevivência de pacientes infectados pelo vírus da imunodeficiência humana (HIV-1 é relacionada à prevenção e ao tratamento eficaz de infecções oportunistas. É conhecido que os principais parâmetros para avaliar a progressão da doença causada pelo HIV-1 são contagem de células T CD4+ e carga viral do HIV-1. Células T regulatórias têm sido foco de intensas investigações dentro do sistema imunológico como também na patogênese de diversas doenças. Sabe-se que as células T reguladoras (Tregs CD4+CD25+FoxP3+ atuam na modulação da ativação imune, funcionando como mediadores críticos da homeostasia imune e da auto-tolerância. Além disso, recentes estudos têm demonstrado que as c

Zero thermal expansion in NaZn13-type La(Fe,Si)13 compounds.

Science.gov (United States)

Wang, Wei; Huang, Rongjin; Li, Wen; Tan, Jie; Zhao, Yuqiang; Li, Shaopeng; Huang, Chuanjun; Li, Laifeng

2015-01-28

A zero thermal expansion material in a pure form of NaZn13-type La(Fe,Si)13 was fabricated. Through optimizing the chemical composition, an isotropic zero thermal expansion material is achieved. The obtained materials exhibit a low expansion of |α| linear thermal expansion) over a broad temperature range (15-150 K). The present study indicates that the thermal expansion behavior of the NaZn13-type La(Fe,Si)13 compounds depends mainly on the content of Si element. This new material is desirable in many fields of industry as a reliable and low-cost zero thermal expansion material.

Thermal expansion of coexistence of ferromagnetism and superconductivity

International Nuclear Information System (INIS)

Hatayama, Nobukuni; Konno, Rikio

2010-01-01

The temperature dependence of thermal expansion of coexistence of ferromag-netism and superconductivity below the superconducting transition temperature T cu of a majority spin conduction band is investigated. Majority spin and minority spin superconducting gaps exist in the coexistent state. We assume that the Curie temperature is much larger than the superconducting transition temperatures. The free energy that Linder et al. [Phys. Rev. B76, 054511 (2007)] derived is used. The thermal expansion of coexistence of ferromagnetism and superconductivity is derived by the application of the method of Takahashi and Nakano [J. Phys.: Condens. Matter 18, 521 (2006)]. We find that we have the anomalies of the thermal expansion in the vicinity of the superconducting transition temperatures.

Instability of a planar expansion wave.

Science.gov (United States)

Velikovich, A L; Zalesak, S T; Metzler, N; Wouchuk, J G

2005-10-01

An expansion wave is produced when an incident shock wave interacts with a surface separating a fluid from a vacuum. Such an interaction starts the feedout process that transfers perturbations from the rippled inner (rear) to the outer (front) surface of a target in inertial confinement fusion. Being essentially a standing sonic wave superimposed on a centered expansion wave, a rippled expansion wave in an ideal gas, like a rippled shock wave, typically produces decaying oscillations of all fluid variables. Its behavior, however, is different at large and small values of the adiabatic exponent gamma. At gamma > 3, the mass modulation amplitude delta(m) in a rippled expansion wave exhibits a power-law growth with time alpha(t)beta, where beta = (gamma - 3)/(gamma - 1). This is the only example of a hydrodynamic instability whose law of growth, dependent on the equation of state, is expressed in a closed analytical form. The growth is shown to be driven by a physical mechanism similar to that of a classical Richtmyer-Meshkov instability. In the opposite extreme gamma - 1 gas with low . Exact analytical expressions for the growth rates are derived for both cases and favorably compared to hydrodynamic simulation results.

Pressure effects on thermal conductivity and expansion of geologic materials

International Nuclear Information System (INIS)

Sweet, J.N.

1979-02-01

Through analysis of existing data, an estimate is made of the effect of pressure or depth on the thermal conductivity and expansion of geologic materials which could be present in radioactive waste repositories. In the case of homogeneous dense materials, only small shifts are predicted to occur at depths less than or equal to 3 km, and these shifts will be insignificant as compared with those caused by temperature variations. As the porosity of the medium increases, the variation of conductivity and expansion with pressure becomes greater, with conductivity increasing and expansion decreasing as pressure increases. The pressure dependence of expansion can be found from data on the temperature variation of the isobaric compressibility. In a worst case estimate, a decrease in expansion of approx. 25% is predicted for 5% porous sandstone at a depth of 3 km. The thermal conductivity of a medium with gaseous inclusions increases as the porosity decreases, with the magnitude of the increase being dependent on the details of the porosity collapse. Based on analysis of existing data on tuff and sandstone, a weighted geometric mean formula is recommended for use in calculating the conductivity of porous rock. As a result of this study, it is recommended that measurement of rock porosity versus depth receive increased attention in exploration studies and that the effect of porosity on thermal conductivity and expansion should be examined in more detail

A Force Method Model for Dynamic Analysis of Flat-Sag Cable Structures

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Xing Ma

2009-01-01

Full Text Available A new force method is proposed for analysing the dynamic behaviour of oscillating cables with small sags. The accepted dynamic model of such cables reduces to a partial differential equation (the equation of motion and an integral equation (the compatibility equation. In the paper, D’Alembert’s travelling wave solution is applied to the partial differential equation (PDE. Substituting the solution into the compatibility and boundary conditions, the governing equation is obtained in terms of the dynamic tension increment. This equation has been named the force method dynamic equation (FMDE. In this way the infinite-degree-of-freedom dynamic system is effectively simplified to a system with only one unknown. Explicit solutions for both single-span and multi-span cable systems are derived. The natural frequencies obtained from the FMDE are shown to be identical to those deduced using the conventional displacement method (DM. Nonlinear governing equations are developed by considering the effect of quadratic and cubic displacement terms. Finally, two examples are presented to illustrate the accuracy of the proposed force method for single and multi-span cable systems subjected to harmonic forces.

Effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4⁺ CD25⁺ Foxp3⁺ Treg in asthma Balb/c mouse.

Science.gov (United States)

Yun, Xiang; Shang, Yunxiao; Li, Miao

2015-01-01

Bronchial asthma is a chronic airway inflammatory disease that involves T lymphocytes. In order to explore the effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4(+) CD25(+) Foxp3(+) Treg in asthma Balb/c mouse, we constructed acute asthma model with ovalbumin to observe the mouse behavior change in Balb/c mice. The expression of GATA-3 mRNA and T-bet mRNA was measured by real-time PCR. The proportion of CD4(+) CD25(+) Foxp3(+) Treg/CD4(+) was determined by flow cytometry. The results demonstrated that oral gavage with Lactobacillus salivarius before sensitization could alleviate the clinical symptoms, airway hyper-reactivity and airway inflammation in asthma mouse to some extent; Lactobacillus salivarius may improve the imbalance of Th1/Th2 in asthma mouse through increasing the expression of T-bet mRNA at the transcriptional level and inhibiting the expression of GATA-3 mRNA simultaneously. CD4(+) CD25(+) Foxp3(+) Treg cells may be involved in the pathogenesis of bronchial asthma, and may be the upstream regulatory mechanism of the improvement of Th1/Th2 imbalance by Lactobacillus salivarius.

The thermal expansion of austenitic manganese and manganese-chromium steels

International Nuclear Information System (INIS)

Richter, F.

1977-01-01

The linear coefficient of thermal expansion was determined by dilatometer for 5 Mn steels and 6 Mn-Cr steels between -196 and +500 0 C. Because of the antiferromagnetic properties, the thermal expansion of austenitic Mn and Mn-Cr steels is determined by the position of the magnetic changeover temperature (Neel temperature), which depends on the chemical composition of the steel. Below the Neel temperature, the thermal coefficient of expansion is greatly reduced by volumetric magnetostriction (Invar effect). For this reason, one can only give approximate values for thermal expansion for all Mn and Mn-Cr steels in the temperature range of -100 0 C to about +100 0 C. (GSC) [de

Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation.

Science.gov (United States)

Chow, Zachary; Mueller, Scott N; Deane, James A; Hickey, Michael J

2013-09-15

Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4⁺ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4⁺ effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.

Trace expansions for mixed boundary problems

Energy Technology Data Exchange (ETDEWEB)

Seeley, Robert T

2002-01-01

We discuss the heat trace expansion for a mixed boundary problem for the Laplace operator acting on sections of some bundle V over a manifold M of dimension d. The boundary is divided in two parts N{sub D} and N{sub N}, intersecting in a smooth submanifold {sigma}. Dirichlet conditions are imposed on N{sub D} - {sigma}, and Neumann conditions on N{sub N} - {sigma}. It turns out that it is also necessary to impose a condition along {sigma}. We then obtain an expansion of the trace of the heat operator with these boundary conditions, containing integrals of the usual terms over the interior and the two parts of the boundary, together with integrals over {sigma} of terms that are 'global' in certain operators on a semicircle. The first nonzero such term is computed; it involves the zeta function of an operator on the semicircle, and depends on the boundary condition along {sigma}. We find that no logarithmic terms occur in the expansion.

IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

Science.gov (United States)

Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

2018-01-01

Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

Drowning unconformity of lacustrine rift basins: A case study from the Dongying Sag in Bohai Bay Basin, China

Science.gov (United States)

Chen, R.; Fan, J.

2015-12-01

The concept of drowning unconformity of lacustrine rift basins was proposed in this paper. This paper utilized 3D seismic data, well-log and the principles methods associated with structural geology, sedimentology and geochemistry, to analyze the drowning unconformity and discuss the origins of drowning unconformity in Dongying Sag in Bohai Bay Basin.Researching on it is not only important for a better understanding of tectonic evolution, palaeogeography and sedimentation of hydrocarbon source rocks, but also a vital guiding significance for the exploration of beach-bar sandstone reservoirs and shale oil.1. The concept of drowning unconformity of lacustrine rift basins is defined. With the consequences of rapid tectonic subsidence in basin, the sharp rise of lake-level and the increased rate of accommodation(A) in basin exceeded the rate of sediment supply(S),namely A>>S, the basin suddenly transformed into deep-water settings from shallow-water settings with sudden change of sediment transport and sediment dispersal patterns. 2.The sequence surface between Sha4 and Sha3 Member of Shahejie Formation is the drowning unconformity(43.5Ma). There are the sedimentary association of the reefs in shallow lacustrine, beach-bar sandstones and glutenite fan bodies under the surface. By contrast, there are the sedimentary association of deep-lake oil shales and shales over the surface. The drowning unconformity in Dongying Sag is a tectonic revolution surface which is changed from extensional tectonics to transtensional tectonics and it is also the surface of discontinuity from shallow lacustrine to deep lacustrine. The responses to sudden changes appeared in the parameters of geophysics, geochemistry and paleontology. 3. With the penetration of India into Asia plate in NNE trending,the subduction zones of Pacific Plate retreated. It caused the rapid downwelling of asthenospheric mantle, followed by the extensive drowning unconformity.

On the Kumar formulation for the temperature dependence of thermal expansivity

International Nuclear Information System (INIS)

Singh, C.P.; Chauhan, R.S.

2004-01-01

The expression for interionic separation obtained earlier by Kumar [Physica. B, Condensed Matter 205 (1995) 175] has been corrected so as to make it compatible with the value of the thermal expansivity at the initial temperature. The values of the interionic separations as a function of temperature calculated for NaCl and KCl using the modified formulation are found to present improved agreement with the experimental data at high temperatures up to the melting temperatures

Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

International Nuclear Information System (INIS)

Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

2011-01-01

For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

Directory of Open Access Journals (Sweden)

Huijts Charlotte M

2011-11-01

Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

Precipitation formation in recrystallized nickel-plated non-sag tungsten wire

International Nuclear Information System (INIS)

Lai, Z.H.

1994-01-01

It is well established that some metals, such as palladium and nickel, can easily penetrate into tungsten by fast diffusion via crystal defects such as grain boundaries and dislocations. As a result of the fast penetration of these so called activators the recrystallization temperature of heavily drawn non-sag tungsten wire can be lower from about 2,000 C to about 1,000 C, thus the application of the tungsten wire, serving as reinforcement material in metal matrix composites used at high temperatures, is limited. An interesting question is in which form these activators exist in the recrystallized tungsten wire. It is generally believed that W-Ni intermediate compounds could form in the recrystallized material, presumably at grain boundaries. The free energy difference between the pure tungsten fibbers and the precipitating W(Ni) solid solution was suggested as the chemical driving force which governed the recrystallization process. The presence of nickel in small particles had also been observed in recrystallized grains of nickel plated tungsten wires using scanning electron microscopy (SEM) and secondary ion mass spectroscopy. These particles were considered to be nickel rich precipitates. However, a detailed investigation of the precipitation process has not been reported. In the present work an investigation of the structure, composition and distribution of nickel rich particles precipitated in recrystallized grains of nickel plated heavily drawn non-sage tungsten wires was carried out using analytical electron microscopy (AEM)

TDHF simulation of the expansion of abraded nuclei

International Nuclear Information System (INIS)

Lacroix, D.; Chomaz, Ph.

1998-03-01

A recent interpretation of the caloric curve based on the expansion of the abraded spectator nuclear is re-analysed in the framework of the Time Dependent Hartree Fock (TDHF) evolution. It is shown that the TDHF dynamics can not be reduced to a single monopolar collective motion at moderate energy. The inclusion of other important collective degrees of freedom may lead to the dynamical creation of hollow structure. Then, low density regions could be locally reached after a long time by the creation of these exotic density profiles. The TDHF simulations do not confirm conclusions made when using an monopolar isentropic expansion. In particular the systematic of the minimum density reached during the expansion (the so-called turning points) appears to be different. (author)

The account of sagging of wires at definition of specific potential factors of air High-Voltage Power Transmission Lines

Directory of Open Access Journals (Sweden)

Suslov V.M.

2005-12-01

Full Text Available The opportunity approached is shown, but more exact as it is usually accepted, the account of sagging of wires at definition of specific potential factors air High-Voltage Power Transmission Lines. The technique of reception of analytical expressions is resulted. For an opportunity of comparison traditional expressions for specific potential factors are resulted also. Communication of the offered and traditional analytical expressions is shown. Offered analytical expressions are not difficult for programming on a personal computer of any class and besides they allow to make an estimation of an error of traditional expressions by means of parallel definition of specific potential factors by both ways.

Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease.

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Sarvari Velaga

Full Text Available In our previous work we could identify defects in human regulatory T cells (Tregs likely favoring the development of graft-versus-host disease (GvHD following allogeneic stem cell transplantation (SCT. Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.

Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice

Science.gov (United States)

Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Breloer, Minka

2014-01-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3+ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3+ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6

Foxp3⁺ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice.

Science.gov (United States)

Blankenhaus, Birte; Reitz, Martina; Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Breloer, Minka

2014-02-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6

Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients

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Jean-Marc Hoffmann

2018-01-01

Full Text Available IntroductionTherapy with chimeric antigen receptor T (CART cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (TN vs. effector (TE T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the TN/TE ratio of CART cells.Materials and methodsCART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL-7/IL-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs and 11 patients with chronic lymphocytic leukemia (CLL for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.ResultsIL-7/IL-15 preferentially induced differentiation into TN, stem cell memory (TSCM: naive CD27+ CD95+, CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (TEM, CD56+ and CD4+ T regulatory (TReg CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CARTN cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CARTN cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CARTN cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CARTN cells in untreated CLL patients. Final TN/TE ratio stayed <0.3 despite stimulation condition for patients

Genesis and distribution pattern of carbonate cements in lacustrine deep-water gravity-flow sandstone reservoirs in the third member of the Shahejie Formation in the Dongying Sag, Jiyang Depression, Eastern China

DEFF Research Database (Denmark)

Yang, Tian; Cao, Yingchang; Friis, Henrik

2018-01-01

The lacustrine deep-water gravity-flow sandstone reservoirs in the third member of the Shahejie Formation are the main exploration target for hydrocarbons in the Dongying Sag, Eastern China. Carbonate cementation is responsible for much of the porosity and permeability reduction in the lacustrine...

Biological Mechanisms Underlying the Ultraviolet Radiation-Induced Formation of Skin Wrinkling and Sagging II: Over-Expression of Neprilysin Plays an Essential Role

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Genji Imokawa

2015-04-01

Full Text Available Our previous studies strongly indicated that the up-regulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. Fortunately, we succeeded in identifying human skin fibroblast-derived elastase as a previously known enzyme, neprilysin or neutral endopeptidase (NEP. We have also characterized epithelial-mesenchymal paracrine cytokine interactions between UVB-exposed-keratinocytes and dermal fibroblasts and found that interleukin-1α and granulocyte macrophage colony stimulatory factor (GM-CSF are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by fibroblasts. On the other hand, direct UVA exposure of human fibroblasts significantly stimulates the secretion of IL-6 and also elicits a significant increase in the gene expression of matrix metallo-protease(MMP-1 as well as neprilysin (to a lesser extent, which is followed by distinct increases in their protein and enzymatic activity levels. Direct UVA exposure of human keratinocytes also stimulates the secretion of IL-6, IL-8 and GM-CSF but not of IL-1 and endothelin-1. These findings suggest that GM-CSF secreted by UVA-exposed keratinocytes as well as IL-6 secreted by UVA-exposed dermal fibroblasts play important and additional roles in UVA-induced sagging and wrinkling by up-regulation of neprilysin and MMP-1, respectively, in dermal fibroblasts.

The expansion rate and size of the universe

CERN Multimedia

Freedman, Wendy L

1998-01-01

The age, evolution and fate of the universe depend on just how fast it is expanding. By measuring the size of the universe using a variety of new techniques, astronomers have recently improved estimates of the expansion rate

Seroprevalence of antibody to NcSAG1 antigen of Neospora caninum in cattle from Western Java, Indonesia.

Science.gov (United States)

Ichikawa-Seki, Madoka; Guswanto, Azirwan; Allamanda, Puttik; Mariamah, Euis Siti; Wibowo, Putut Eko; Nishikawa, Yoshifumi

2016-01-01

Neospora caninum can cause fetal abortion and neonatal mortality in cattle, and is a cause of economic concern worldwide. This study aimed to determine the prevalence of Neospora caninum-specific antibodies in cattle from Western Java, Indonesia. Serum samples from 991 cattle from 21 locations were tested for antibodies to N. caninum by using an enzyme-linked immunosorbent assay (ELISA) on the basis of recombinant NcSAG1. The overall seroprevalence was 16.6%, ranging from 0 to 87.5% in the sampled locations. The results of this study indicate latent infection rates of sampled animals were different in each location. Further studies are necessary to elucidate the relationship between N. caninum infection and abortion in cattle, and to identify risk factors for infection in high-prevalence environments.

Diamond Thermal Expansion Measurement Using Transmitted X-ray Back-diffraction.

OpenAIRE

Giles, Carlos; Adriano, Cris; Lubambo, Adriana Freire; Cusatis, Cesar; Mazzaro, Irineu; Hönnicke, Marcelo Goncalves

2015-01-01

The linear thermal expansion coefficient of diamond has been measured using forward-diffracted profiles in X-ray backscattering. This experimental technique is presented as an alternative way of measuring thermal expansion coefficients of solids in the high-resolution Bragg backscattering geometry without the intrinsic difficulty of detecting the reflected beam. The temperature dependence of the lattice parameter is obtained from the high sensitivity of the transmitted profiles to the Bragg a...

Live and heat-killed probiotic Lactobacillus casei Lbs2 protects from experimental colitis through Toll-like receptor 2-dependent induction of T-regulatory response.

Science.gov (United States)

Thakur, Bhupesh Kumar; Saha, Piu; Banik, George; Saha, Dhira Rani; Grover, Sunita; Batish, Virender Kumar; Das, Santasabuj

2016-07-01

Inflammatory bowel disease (IBD) is a group of inflammatory disorders of the intestine caused by dysregulated T-cell mediated immune response against commensal microflora. Probiotics are reported as therapeutically effective against IBD. However, variable efficacy of the live probiotic strains, difference in survival and persistence in the gut between the strains and the lack of insight into the mechanisms of probiotic action limit optimal therapeutic efficacy. Our aims were to evaluate the lactobacillus strains isolated from the North Indian population for the generation of regulatory cells and cytokines in the intestine, to study their effects on pro-inflammatory mediators in the mouse model of inflammatory bowel disease and to explore the underlying mechanisms of their actions. Among the selected lactobacillus strains, Lactobacillus casei Lbs2 (MTCC5953) significantly suppressed lipopolysaccharide-induced pro-inflammatory cytokine (TNF-alpha, IL-6) secretion. Both live and heat-killed Lbs2 polarized Th0 cells to T-regulatory (Treg) cells in vitro, increased the frequency of FoxP3(+) Treg cells in the mesenteric lymph nodes (MLNs) and alleviated macroscopic and histopathological features of colitis in probiotic-fed mice. Moreover, the levels of IL-12, TNF-alpha and IL-17A were suppressed, while IL-10 and TGF-beta levels were augmented in the colonic tissues of Lbs2-treated mice. The induced Treg (iTreg) cells secreted IL-10 and TGF-beta and exerted suppressive effects on the proliferation of effector T-cells. Adoptive transfer of iTreg cells ameliorated the disease manifestations of murine colitis and suppressed the levels of TNF-alpha and IL-17A. Finally, Lbs2 effects were mediated by Toll-like receptor 2 (TLR2) activation on the dendritic cells. This study identified live and heat-killed Lbs2 as putative therapeutic candidates against IBD and highlighted their Toll-like receptor 2-dependent immunomodulatory and regulatory function. Copyright © 2016 Elsevier B

Separable pole expansions in four-nucleon bound state calculations

International Nuclear Information System (INIS)

Sofianos, S.A.; Fiedeldey, H.; Haberzettl, H.; Sandhas, W.

1982-04-01

We compare the utility of the Generalized Unitary Pole Expansion (GUPE) and the Energy-Dependent Pole Expansion (EDPE) for the three-body subsystem amplitudes in four-body state calculations for a variety of separable and local nucleon-nucleon interactions. It is found that, with the EDPE, the four-body binding energy is well reproduced with only two terms each for the (2+2)- and the (3+1)-subsystem, respectively, while the GUPE requires three terms for the (3+1)-channel and four terms for the (2+2)-channel. We thus conclude that pole dominance is of greater importance for the GUPE than for EDPE, which works equally well for both types of subsystems. It is found that both methods, in particular the EDPE, converge more rapidly with increasing repulsion in the two-body interaction, i.e. the more realistic the interaction becomes. Both expansions require similar computing times for a converged calculation and are about 15-20 times faster than the widely used Hilbert-Schmidt Expansion (HSE). The respective merits of the two pole expansions are discussed and compared with the HSE. (orig.)

The Thermal Expansion Of Feldspars

Science.gov (United States)

Hovis, G. L.; Medford, A.; Conlon, M.

2009-12-01

Hovis and others (1) investigated the thermal expansion of natural and synthetic AlSi3 feldspars and demonstrated that the coefficient of thermal expansion (α) decreases significantly, and linearly, with increasing room-temperature volume (VRT). In all such feldspars, therefore, chemical expansion limits thermal expansion. The scope of this work now has been broadened to include plagioclase and Ba-K feldspar crystalline solutions. X-ray powder diffraction data have been collected between room temperature and 925 °C on six plagioclase specimens ranging in composition from anorthite to oligoclase. When combined with thermal expansion data for albite (2,3,4) a steep linear trend of α as a function of VRT emerges, reflecting how small changes in composition dramatically affect expansion behavior. The thermal expansion data for five synthetic Ba-K feldspars ranging in composition from 20 to 100 mole percent celsian, combined with data for pure K-feldspar (3,4), show α-VRT relationships similar in nature to the plagioclase series, but with a slope and intercept different from the latter. Taken as a group all Al2Si2 feldspars, including anorthite and celsian from the present study along with Sr- (5) and Pb-feldspar (6) from other workers, show very limited thermal expansion that, unlike AlSi3 feldspars, has little dependence on the divalent-ion (or M-) site occupant. This apparently is due to the necessitated alternation of Al and Si in the tetrahedral sites of these minerals (7), which in turn locks the tetrahedral framework and makes the M-site occupant nearly irrelevant to expansion behavior. Indeed, in feldspar series with coupled chemical substitution it is the change away from a 1:1 Al:Si ratio that gives feldspars greater freedom to expand. Overall, the relationships among α, chemical composition, and room-temperature volume provide useful predictive tools for estimating feldspar thermal expansion and give insight into the controls of expansion behavior in

Commercial Building Motor Protection Response Report

Energy Technology Data Exchange (ETDEWEB)

James, Daniel P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kueck, John [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2015-06-17

When voltages recover, motors may immediately reenergize and reaccelerate, or delay for a few minutes, or stay stalled. The estimated motor response is given for both the voltage sag magnitude and voltage sag duration. These response estimates are based on experience and available test data. Good data is available for voltage sag response for many components such as relays and contactors, but little data is available for both voltage sag and recovery response. The tables in Appendix A include data from recent voltage sag and recovery tests performed by SCE and BPA on air conditioners and energy management systems. The response of the motor can vary greatly depending on the type of protection and control. The time duration for the voltage sag consists of those times that are of interest for bulk power system modelers.

Mast cell degranulation breaks peripheral tolerance.

Science.gov (United States)

de Vries, V C; Wasiuk, A; Bennett, K A; Benson, M J; Elgueta, R; Waldschmidt, T J; Noelle, R J

2009-10-01

Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.

A Pedagogical Approach to the Magnus Expansion

Science.gov (United States)

Blanes, S.; Casas, F.; Oteo, J. A.; Ros, J.

2010-01-01

Time-dependent perturbation theory as a tool to compute approximate solutions of the Schrodinger equation does not preserve unitarity. Here we present, in a simple way, how the "Magnus expansion" (also known as "exponential perturbation theory") provides such unitary approximate solutions. The purpose is to illustrate the importance and…

Experimental Investigation of Reynolds Number Effects on Test Quality in a Hypersonic Expansion Tube

Science.gov (United States)

Rossmann, Tobias; Devin, Alyssa; Shi, Wen; Verhoog, Charles

2017-11-01

Reynolds number effects on test time and the temporal and spatial flow quality in a hypersonic expansion tube are explored using high-speed pressure, infrared optical, and Schlieren imaging measurements. Boundary layer models for shock tube flows are fairly well established to assist in the determination of test time and flow dimensions at typical high enthalpy test conditions. However, the application of these models needs to be more fully explored due to the unsteady expansion of turbulent boundary layers and contact regions separating dissimilar gasses present in expansion tube flows. Additionally, expansion tubes rely on the development of a steady jet with a large enough core-flow region at the exit of the acceleration tube to create a constant velocity region inside of the test section. High-speed measurements of pressure and Mach number at several locations within the expansion tube allow for the determination of an experimental x-t diagram. The comparison of the experimentally determined x-t diagram to theoretical highlights the Reynolds number dependent effects on expansion tube. Additionally, spatially resolved measurements of the Reynolds number dependent, steady core-flow in the expansion tube viewing section are shown. NSF MRI CBET #1531475, Lafayette College, McCutcheon Foundation.

CCR 20th Anniversary Commentary: From Regulatory T Cells to Checkpoint Monoclonal Antibodies--Immuno-oncology Advances Clinical Cancer Research.

Science.gov (United States)

Wolf, Dominik; Wolf, Anna Maria

2015-06-15

Immune escape is a hallmark of cancer development and metastasis. Regulatory T cells (Treg) are potent inhibitors of cancer immune surveillance but also prevent inflammation-driven tumorigenesis. The study by Wolf and colleagues, which was published in the February 2003 issue of Clinical Cancer Research, showed the expansion of Treg in solid cancer patients, providing a deeper understanding of cancer immune escape mechanisms that later set the stage for the development of scientific breakthroughs in cancer immunotherapy. ©2015 American Association for Cancer Research.

DG Allocation Based on Reliability, Losses and Voltage Sag Considerations: an expert system approach

Directory of Open Access Journals (Sweden)

Sahar Abdel Moneim Moussa