Sample records for nach epqc 4th

  1. 2. 3/4 VIEW OF NACHES RIVER BRIDGE, LOOKING SOUTHWEST (BURLINGTON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. 3/4 VIEW OF NACHES RIVER BRIDGE, LOOKING SOUTHWEST (BURLINGTON NORTHERN RAILROAD BRIDGE ON EXTREME LEFT) - Yakima Valley Transportation Company Interurban Railroad, Naches River Bridge, Yakima, Yakima County, WA

  2. 17. 4th floor roof, view south, 4th and 5th floor ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. 4th floor roof, view south, 4th and 5th floor setback to left and atrium structure to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  3. 166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH AVE. FROM BUILDING 44 SHOWING, FROM LEFT TO RIGHT, BUILDING 46, 48, 55, AND 50 (PART OF ENLISTED BARRACKS COMPLEX), AND BUILDINGS 17, 16, 484, 483, 374, AND 375 (IN THE WAREHOUSE COMPLEX). - Quonset Point Naval Air Station, Roger Williams Way, North Kingstown, Washington County, RI

  4. Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.

    PubMed

    Orlova-Fink, Nina; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-10-23

    The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.

  5. Late Quaternary Glaciation of the Naches River Drainage Basin, Washington Cascades

    NASA Astrophysics Data System (ADS)

    Sheffer, H. B.; Goss, L.; Shimer, G.; Carson, R. J.

    2014-12-01

    The Naches River drainage basin east of Mount Rainer includes tributary valleys of the Little Naches, American, Bumping, and Tieton rivers. An investigation of surface boulder frequency, weathering rind thicknesses, and soil development on moraines in these valleys identified two stages of Pleistocene glaciations in the American, Bumping, and Tieton drainages, followed by Neoglaciation. These stages include a more extensive early glaciation (Hayden Creek?), and the later Evans Creek Glaciation (25-15 ka). Thick forest cover, limited road cuts, and widespread post-glacial mass wasting hamper efforts to determine the maximum extent of glaciation. However, glacial striations at Chinook Pass, moraine complexes in the vicinity of Goose Egg Mountain, ice-transported boulders and striations on Pinegrass Ridge, and a boulder field possibly derived from an Evans Creek jökulhaup in the Tieton River valley, all point to extensive Pleistocene ice in the central tributaries of the Naches River. Lowest observed ice elevations in the Tieton (780 m), Bumping (850 m), and American (920 m) drainages increase towards the north, while glacial lengths decrease from 40 to 28 km. The Little Naches is the northernmost drainage in the study, but despite a maximum elevation (1810 m) that exceeds the floor of ice caps to the south, glacially-derived sediments are not evident and the surrounding peaks lack cirques. The absence of ice in the Little Naches drainage, along with the systematic northward change in glacial length and lowest observed ice elevations in the other drainages, are likely due to a precipitation shadow northeast of Mount Rainier. In contrast, the source of glacial ice in the Tieton drainage to the southeast was the Goat Rocks peaks. Ground-based study of neoglacial moraines and analysis of 112 years of topographic maps and satellite imagery point to rapid retreat of the remaining Goat Rocks glaciers following the Little Ice Age.

  6. The Leap into 4th Grade

    ERIC Educational Resources Information Center

    Anderson, Mike

    2011-01-01

    Fourth grade is a pivotal year, in which students commonly face increased academic demands. According to Anderson, teachers can help students make a smooth transition to 4th grade by introducing these new challenges in ways that are in line with 4th graders' common developmental characteristics: incredible energy and emotion, industriousness and…

  7. Ab initio studies of Th3N4, Th2N3 and Th2N2(NH)

    NASA Astrophysics Data System (ADS)

    Obodo, K. O.; Chetty, N.

    2014-09-01

    Using density functional theory within the Perdew-Burke-Ernzerhof generalized gradient approximation [GGA (PBE)] implemented in the VASP codes, we investigate the structural, elastic and electronic properties of Th3N4, Th2N3 and Th2N2(NH). The calculated structural properties of these thorium-based nitrides are in good agreement with experimental data. We observe that all the Th-N based compounds that we considered are energetically favorable and elastically stable. We find that Th3N4 is semiconducting with a band gap of 1.59 eV, which compares well with the experimental band gap of 1.7 eV and we find Th2N3 to be metallic. Th2N2(NH), which is crystallographically equivalent to Th2N3, is insulating with a band gap of 2.12 eV. This is due to the -(NH) group that effects a shifting of the energy bands that results in the opening of a gap at the Fermi-level. The Th-N based compounds that we considered are predominantly ionic.

  8. Trapping of Li(+) Ions by [ThFn](4-n) Clusters Leading to Oscillating Maxwell-Stefan Diffusivity in the Molten Salt LiF-ThF4.

    PubMed

    Chakraborty, Brahmananda; Kidwai, Sharif; Ramaniah, Lavanya M

    2016-08-18

    A molten salt mixture of lithium fluoride and thorium fluoride (LiF-ThF4) serves as a fuel as well as a coolant in the most sophisticated molten salt reactor (MSR). Here, we report for the first time dynamic correlations, Onsager coefficients, Maxwell-Stefan (MS) diffusivities, and the concentration dependence of density and enthalpy of the molten salt mixture LiF-ThF4 at 1200 K in the composition range of 2-45% ThF4 and also at eutectic composition in the temperature range of 1123-1600 K using Green-Kubo formalism and equilibrium molecular dynamics simulations. We have observed an interesting oscillating pattern for the MS diffusivity for the cation-cation pair, in which ĐLi-Th oscillates between positive and negative values with the amplitude of the oscillation reducing as the system becomes rich in ThF4. Through the velocity autocorrelation function, vibrational density of states, radial distribution function analysis, and structural snapshots, we establish an interplay between the local structure and multicomponent dynamics and predict that formation of negatively charged [ThFn](4-n) clusters at a higher ThF4 mole % makes positively charged Li(+) ions oscillate between different clusters, with their range of motion reducing as the number of [ThFn](4-n) clusters increases, and finally Li(+) ions almost get trapped at a higher ThF4% when the electrostatic force on Li(+) exerted by various surrounding clusters gets balanced. Although reports on variations of density and enthalpy with temperature exist in the literature, for the first time we report variations of the density and enthalpy of LiF-ThF4 with the concentration of ThF4 (mole %) and fit them with the square root function of ThF4 concentration, which will be very useful for experimentalists to obtain data over a range of concentrations from fitting the formula for design purposes. The formation of [ThFn](4-n) clusters and the reduction in the diffusivity of the ions at a higher ThF4% may limit the

  9. The 4th Thermodynamic Principle?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montero Garcia, Jose de la Luz; Novoa Blanco, Jesus Francisco

    2007-04-28

    It should be emphasized that the 4th Principle above formulated is a thermodynamic principle and, at the same time, is mechanical-quantum and relativist, as it should inevitably be and its absence has been one of main the theoretical limitations of the physical theory until today.We show that the theoretical discovery of Dimensional Primitive Octet of Matter, the 4th Thermodynamic Principle, the Quantum Hexet of Matter, the Global Hexagonal Subsystem of Fundamental Constants of Energy and the Measurement or Connected Global Scale or Universal Existential Interval of the Matter is that it is possible to be arrived at a global formulationmore » of the four 'forces' or fundamental interactions of nature. The Einstein's golden dream is possible.« less

  10. 20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH FLOOR WITH WHITE GLAZED TERRA COTTA SILL AND HEADERS. MULLIONS ARE ORANGE BROWN BRICKS LIKE THE WALLS. BRICKS ARE IN FLEMISH BOND PATTERN. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  11. Comparing Science Learning among 4th-, 5th-, and 6th-Grade Students: STS versus Textbook-Based Instruction

    ERIC Educational Resources Information Center

    Yager, Robert E.; Choi, AeRan; Yager, Stuart O.; Akcay, Hakan

    2009-01-01

    Fifteen 4th-, 5th-, and 6th-grade teachers from five school districts each taught two sections of science--one with a Science-Technology-Society (STS) approach and the other with a more traditional textbook approach in which basic science concepts were the major organizers. Local, current, and personally relevant issues provided the context and…

  12. Thermodynamic assessment of the LiF-ThF4-PuF3-UF4 system

    NASA Astrophysics Data System (ADS)

    Capelli, E.; Beneš, O.; Konings, R. J. M.

    2015-07-01

    The LiF-ThF4-PuF3-UF4 system is the reference salt mixture considered for the Molten Salt Fast Reactor (MSFR) concept started with PuF3. In order to obtain the complete thermodynamic description of this quaternary system, two binary systems (ThF4-PuF3 and UF4-PuF3) and two ternary systems (LiF-ThF4-PuF3 and LiF-UF4-PuF3) have been assessed for the first time. The similarities between CeF3/PuF3 and ThF4/UF4 compounds have been taken into account for the presented optimization as well as in the experimental measurements performed, which have confirmed the temperatures predicted by the model. Moreover, the experimental results and the thermodynamic database developed have been used to identify potential compositions for the MSFR fuel and to evaluate the influence of partial substitution of ThF4 by UF4 in the salt.

  13. Increase Reading Fluency of 4th and 5th Grade Students with Learning Disabilities Using Readers' Theatre

    ERIC Educational Resources Information Center

    Mountford, Kathy A.

    2007-01-01

    The following Action Research Project Report is to improve the oral reading fluency of the 4th and 5th grade students with learning disabilities. The targeted population participating in this study consisted of a total of ten participants of which five were 4th grade students and five were 5th grade students located in a middle class community…

  14. USNAVSO/4th Fleet

    Science.gov Websites

    . FOURTH Fleet (USNAVSO/FOURTHFLT) employs maritime forces in cooperative maritime security operations in €­(Hidden)‬ USNAVSO/4th Fleet News Retrieving Data Links Secretary of the Navy Chief of Naval Operations Department of Defense U.S. Southern Command SOCIAL MEDIA Quick Links US Navy Recruiting | No Fear Act Data

  15. Systematically frameshifting by deletion of every 4th or 4th and 5th nucleotides during mitochondrial transcription: RNA self-hybridization regulates delRNA expression.

    PubMed

    Seligmann, Hervé

    2016-01-01

    In mitochondria, secondary structures punctuate post-transcriptional RNA processing. Recently described transcripts match the human mitogenome after systematic deletions of every 4th, respectively every 4th and 5th nucleotides, called delRNAs. Here I explore predicted stem-loop hairpin formation by delRNAs, and their associations with delRNA transcription and detected peptides matching their translation. Despite missing 25, respectively 40% of the nucleotides in the original sequence, del-transformed sequences form significantly more secondary structures than corresponding randomly shuffled sequences, indicating biological function, independently of, and in combination with, previously detected delRNA and thereof translated peptides. Self-hybridization decreases delRNA abundances, indicating downregulation. Systematic deletions of the human mitogenome reveal new, unsuspected coding and structural informations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The 4th order GISS model of the global atmosphere

    NASA Technical Reports Server (NTRS)

    Kalnay-Rivas, E.; Bayliss, A.; Storch, J.

    1977-01-01

    The new GISS 4th order model of the global atmosphere is described. It is based on 4th order quadratically conservative differences with the periodic application of a 16th order filter on the sea level pressure and potential temperature equations, a combination which is approximately enstrophy conserving. Several short range forecasts indicate a significant improvement over 2nd order forecasts with the same resolution (approximately 400 km). However the 4th order forecasts are somewhat inferior to 2nd order forecasts with double resolution. This is probably due to the presence of short waves in the range between 1000 km and 2000 km, which are computed more accurately by the 2nd order high resolution model. An operation count of the schemes indicates that with similar code optimization, the 4th order model will require approximately the same amount of computer time as the 2nd order model with the same resolution. It is estimated that the 4th order model with a grid size of 200 km provides enough accuracy to make horizontal truncation errors negligible over a period of a week for all synoptic scales (waves longer than 1000 km).

  17. Assessment of an Engineering Technology Outreach Program for 4th-7th Grade Girls

    ERIC Educational Resources Information Center

    Dell, Elizabeth M.; Christman, Jeanne; Garrick, Robert D.

    2011-01-01

    This paper describes a workshop led by female Engineering Technology students, with support from female faculty, to provide an introduction to Engineering Technology to 4th-7th grade girls through a series of interactive laboratory experiments. This outreach program was developed to improve attitudes towards science and engineering in middle…

  18. CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production.

    PubMed

    Romagnani, Paola; Maggi, Laura; Mazzinghi, Benedetta; Cosmi, Lorenzo; Lasagni, Laura; Liotta, Francesco; Lazzeri, Elena; Angeli, Roberta; Rotondi, Mario; Filì, Lucia; Parronchi, Paola; Serio, Mario; Maggi, Enrico; Romagnani, Sergio; Annunziato, Francesco

    2005-12-01

    Two variants of the CXCR3 receptor exist, one (CXCR3-A) reactive with CXCL9, CXCL10, and CXCL11 and the other (CXCR3-B) also reactive with CXCL4. Both variants are contemporarily expressed by human T cells. We sought to investigate the in vitro effects of CXCL10 and CXCL4 on the production of TH1 or TH2 cytokines. The cytokine profile of antigen-specific human CD4+ T-cell lines obtained in the absence or presence of CXCL10 or CXCL4 was evaluated by means of quantitative RT-PCR, flow cytometry, and ELISA. CXCL10 upregulated IFN-gamma and downregulated IL-4, IL-5, and IL-13 production, whereas CXCL4 downregulated IFN-gamma and upregulated TH2 cytokines. Similar effects were also observed on polyclonally activated pure naive CD4+ T cells. The opposite effects of CXCL10 and CXCL4 on TH1 and TH2 cytokine production were inhibited by an anti-CXCR3 antibody able to neutralize both CXCR3-A and CXCR3-B and were apparently related to the activation of distinct signal transduction pathways. Moreover, CXCL10 upregulated mRNA levels of T-box expressed in T cells and downregulated GATA-3 expression, whereas CXCL4 downregulated T-box expressed in T cells and upregulated GATA-3. Finally, CXCL4, but not CXCL10, induced direct activation of IL-5 and IL-13 promoters. CXCL10 and CXCL4 exert opposite effects on the production of human TH1 and TH2 cytokines, likely through their respective interaction with CXCR3-A or CXCR3-B and the consequent activation of different signal transduction pathways. This might represent an internal regulatory pathway of TH cell responses and might contribute to the modulation of chronic inflammatory reactions, including allergy.

  19. Releasing Ski-Smad4 mediated suppression is essential to license Th17 differentiation

    PubMed Central

    Zhang, Song; Takaku, Motoki; Zou, Liyun; Gu, Ai-di; Chou, Wei-chun; Zhang, Ge; Wu, Bing; Kong, Qing; Thomas, Seddon Y.; Serody, Jonathan S.; Chen, Xian; Xu, Xiaojiang; Wade, Paul A.; Cook, Donald N.; Ting, Jenny P.; Wan, Yisong Y.

    2017-01-01

    Th17 cells are critically involved in host defense, inflammation, and autoimmunity1–5. TGF-β is instrumental in Th17 differentiation by cooperating with IL-66,7. Yet, the mechanism of how TGF-β enables Th17 differentiation remains elusive. Here we reveal that TGF-β licenses Th17 differentiation by releasing Ski-Smad4-complex suppressed RORγt expression. We found serendipitously that, unlike wild-type T cells, Smad4-deficient T cells differentiated into Th17 cells in the absence of TGF-β signaling in a RORγt-dependent manner. Ectopic Smad4 expression suppressed the RORγt expression and Th17 differentiation of Smad4-deficient T cells. Unexpectedly however, TGF-β neutralized Smad4 mediated suppression without affecting Smad4 binding to Rorc locus. Proteomic analysis revealed that Smad4 interacted with Ski, a transcriptional repressor degraded upon TGF-β stimulation. Ski controlled the histone acetylation/de-acetylation of Rorc locus and Th17 differentiation via Smad4 because ectopic Ski expression inhibited H3K9Ac of Rorc locus, Rorc expression and Th17 differentiation in a Smad4-dependent manner. Therefore, TGF-β-induced disruption of Ski releases Ski-Smad4 complex imposed suppression of RORγt to license Th17 differentiation. This study reveals a critical mechanism by which TGF-β controls Th17 differentiation and uncovers Ski-Smad4 axis as a potential therapeutic target for treating Th17 related diseases. PMID:29072299

  20. Subjective depth of field in presence of 4th-order and 6th-order Zernike spherical aberration using adaptive optics technology.

    PubMed

    Benard, Yohann; Lopez-Gil, Norberto; Legras, Richard

    2010-12-01

    To study the impact on the subjective depth of field of 4th-order spherical aberration and its combination with 6th-order spherical aberration and analyze the accuracy of image-quality metrics in predicting the impact. Laboratoire Aimé Cotton, Centre National de la Recherche Scientifique, Université Paris-Sud, Orsay, France. Case series. Subjective depth of field was defined as the range of defocus at which the target (3 high-contrast letters at 20/50) was perceived acceptable. Depth of field was measured using 0.18 diopter (D) steps in young subjects with the addition of the following spherical aberration values: ±0.3 μm and ±0.6 μm 4th-order spherical aberration with 3.0 mm and 6.0 mm pupils and ±0.3 μm 4th-order spherical aberration with ±0.1 μm 6th-order spherical aberration for 6.0 mm pupils. The addition of ±0.3 and ±0.6 μm 4th-order spherical aberration increased depth of field by 30% and 45%, respectively. The combination of 4th-order spherical aberration and 6th-order spherical aberration of opposite signs increased depth of field more than 4th-order spherical aberration alone (ie, 63%), while the combination of 4th-order spherical aberration and 6th-order spherical aberration of the same signs did not (ie, 24%). Whereas the midpoint of the depth of field could be predicted by image-quality metrics, none was found a good predictor of objectionable depth of field. Subjective depth of field increased when 4th-order spherical aberration and 6th-order spherical aberration of opposite signs were added but could not be predicted with image-quality metrics. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  1. Temperature-resolved study of three [M(M'O4)4(TBPO)4] complexes (MM' = URe, ThRe, ThTc).

    PubMed

    Helliwell, Madeleine; Collison, David; John, Gordon H; May, Iain; Sarsfield, Mark J; Sharrad, Clint A; Sutton, Andrew D

    2006-02-01

    The crystal structures of the title complexes were measured at several temperatures between room temperature and 100 K. Each sample shows reversible crystal-to-crystal phase transitions as the temperature is varied. The behaviour of [U(ReO4)4(TBPO)4] (I) and [Th(ReO4)4(TBPO)4] (II) (TBPO = tri-n-butylphosphine oxide) is very similar; at room temperature, crystals of (I) and (II) are isostructural, with space group I42m, and reducing the temperature to 100 K causes a lowering of the space-group symmetry to C-centred cells, space groups Cc for (I) and Cmc2(1) for (II). The variation of lattice symmetry of [Th(TcO4)4(TBPO)4] (III) was found to be somewhat different, with the body-centred cubic space group, I43m, occurring at 293 K, a reduction of symmetry at 230 K to the C-centred orthorhombic space group, Cmc2(1), and a further transition to the primitive orthorhombic space group, Pbc2(1), below 215 K. Elucidation of the correct space-group symmetry and the subsequent refinement was complicated in some cases by the twinning by pseudo-merohedry that arises from the lowering of the space-group symmetry, occurring as the temperature is reduced. All three of the crystal structures determined at room temperature have high atomic displacement parameters, particularly of the (n)Bu groups, and (III) shows disorder of some of the O atoms. The structures in the space group Cmc2(1), show some disorder of nBu groups, but are otherwise reasonably well ordered; the structures of (I) in Cc and (III) in Pbc2(1) are ordered, even to the ends of the alkyl chains. Inter-comparison of the structures measured below 293 K, using the program OFIT from the SHELXTL package, showed that generally, they are remarkably alike, with weighted r.m.s. deviations of the M, M' and P atoms of less than 0.1 A, as are the 293 K structures of (I) and (II) with their low-temperature counterparts. However, the structure of (III) measured in the space group Cmc2(1) is significantly different from both the

  2. Kinetics of Cathode Processes in Separation of Thorium from Molten Salts. Part I. Investigation of ThF$sub 4$ and ThF$sub 4$-CaF$sub 2$; KINETYKA PROCESU KATODOWEGO PRZY OSADZANIU TORU ZE STOPIONYCH SOLI. CZESC I. BADANIA ThF$sub 4$ I ThF$sub 4$-CaF$sub 2$

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mints, S.; Rafal'skii, V.

    1961-09-01

    The current-intensity curves of non-electrolyzed salts and the curves of time-intensity and current-intensity in electrolyzed salts were plotted for molten ThF/sub 4/ and ThF /sub 4/CaF/sub 2/. The intensity of salt disintegration was determined, and electric conductivity in electrolyte was observed. (trauth)

  3. A novel acute HIV infection staging system based on 4th generation immunoassay.

    PubMed

    Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

    2013-05-29

    Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

  4. The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies.

    PubMed

    Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

    2014-08-01

    Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. © 2014 The British Pharmacological Society.

  5. The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies

    PubMed Central

    Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

    2014-01-01

    BACKGROUND AND PURPOSE Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. EXPERIMENTAL APPROACHES To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. KEY RESULTS BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. CONCLUSION AND IMPLICATIONS Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. PMID:24750073

  6. Promoting Maternal and Infant Health in the 4th Trimester

    ERIC Educational Resources Information Center

    Verbiest, Sarah B.; Tully, Kristin P.; Stuebe, Alison M.

    2017-01-01

    The "4th trimester" refers to the transition period after childbirth when infants are adjusting to life outside the womb and mothers are adjusting to new parenthood. This critical period is marked by significant biological, psychological, and social changes, which are currently insufficiently supported. The 4th trimester perspective…

  7. [The comparison of 4th, 5th and 6th year medical students knowledge of rules and practical skills in the interpretation of electrocardiograms at Jagiellonian University].

    PubMed

    Pudło, Joanna; Wierdak, Mateusz; Macioł, Karolina; Gumul, Katarzyna; Lelakowski, Jacek

    2012-01-01

    The electrocardiogram (ECG) examination is one of the most frequent administered diagnostic tests. It is commonly ordered by General Practitioners, and it has became a routinely administered examination during admission to the hospital. During their studies, medical students has numerous opportunities to review and interpret the results of these tests. The aim of our research was to statistically compare and contrast the knowledge of the rules and practical skills in the interpretation of ECGs in 4th, 5th and 6th year medical students at Jagiellonian University. We wanted to better define in which year the students acquire the most of their clinical skills and determine if 6th year students have sufficient knowledge and skills to adequately perform in their future career. We additionally wanted to understand from which source students draw their knowledge of the ECG. The population of 249- 4th, 5th and 6th year medical students of Jagiellonian University were asked to reply to an anonymous questionnaire. The questionnaire was comprised of three parts. The fist part contains four simple ECGs (STEMI, RBBB, PVC, normogram--sinus rhythm). The second part contained six questions regarding their theoretical knowledge. The third part contained seven questions which evaluated the students' background and approach to the problem. Students filled the questionnaire without prior preparation to avoid the short-term "examination knowledge". The question that was most frequent answered correctly was question regarding the proper time (in milliseconds) of QRS complex (24.1%). Differences in the percentage of correct answers to questionnaire amongst 4th and 5th year students were statistically uncharacteristic. The percentage of correct answers of 6th year students increased by about 16% (p < 0.0001). The comparison of answers between 6th year students - who in prior semester completed a cardiology course (group A 6th year) and 6th year students who did not yet complete cardiology

  8. Size resolved infrared spectroscopy of Na(CH3OH)n (n = 4-7) clusters in the OH stretching region: unravelling the interaction of methanol clusters with a sodium atom and the emergence of the solvated electron.

    PubMed

    Forck, Richard M; Pradzynski, Christoph C; Wolff, Sabine; Ončák, Milan; Slavíček, Petr; Zeuch, Thomas

    2012-03-07

    Size resolved IR action spectra of neutral sodium doped methanol clusters have been measured using IR excitation modulated photoionisation mass spectroscopy. The Na(CH(3)OH)(n) clusters were generated in a supersonic He seeded expansion of methanol by subsequent Na doping in a pick-up cell. A combined analysis of IR action spectra, IP evolutions and harmonic predictions of IR spectra (using density functional theory) of the most stable structures revealed that for n = 4, 5 structures with an exterior Na atom showing high ionisation potentials (IPs) of ~4 eV dominate, while for n = 6, 7 clusters with lower IPs (~3.2 eV) featuring fully solvated Na atoms and solvated electrons emerge and dominate the IR action spectra. For n = 4 simulations of photoionisation spectra using an ab initio MD approach confirm the dominance of exterior structures and explain the previously reported appearance IP of 3.48 eV by small fractions of clusters with partly solvated Na atoms. Only for this cluster size a shift in the isomer composition with cluster temperature has been observed, which may be related to kinetic stabilisation of less Na solvated clusters at low temperatures. Features of slow fragmentation dynamics of cationic Na(+)(CH(3)OH)(6) clusters have been observed for the photoionisation near the adiabatic limit. This finding points to the relevance of previously proposed non-vertical photoionisation dynamics of this system.

  9. Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

    PubMed Central

    LAGIER, B; LEBEL, B; BOUSQUET, J; PÈNE, J

    1997-01-01

    Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio ⩾ 0.1 and ⩽1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma. PMID:9182905

  10. Comparison of Visual Assessment of Breast Density in BI-RADS 4th and 5th Editions With Automated Volumetric Measurement.

    PubMed

    Youk, Ji Hyun; Kim, So Jung; Son, Eun Ju; Gweon, Hye Mi; Kim, Jeong-Ah

    2017-09-01

    The purpose of this study was to compare visual assessments of mammographic breast density by radiologists using BI-RADS 4th and 5th editions in correlation with automated volumetric breast density measurements. A total of 337 consecutive full-field digital mammographic examinations with standard views were retrospectively assessed by two radiologists for mammographic breast density according to BI-RADS 4th and 5th editions. Fully automated measurement of the volume of fibroglandular tissue and total breast and percentage breast density was performed with a commercially available software program. Interobserver and intraobserver agreement was assessed with kappa statistics. The distributions of breast density categories for both editions of BI-RADS were compared and correlated with volumetric data. Interobserver agreement on breast density category was moderate to substantial (κ = 0.58-0.63) with use of BI-RADS 4th edition and substantial (κ = 0.63-0.66) with use of the 5th edition but without significant difference between the two editions. For intraobserver agreement between the two editions, the distributions of density category were significantly different (p < 0.0001), the proportions of dense breast increased, and the proportion of fatty breast decreased with use of the 5th edition compared with the 4th edition (p < 0.0001). All volumetric breast density data, including percentage breast density, were significantly different among density categories (p < 0.0001) and had significant correlation with visual assessment for both editions of BI-RADS (p < 0.01). Assessment using BI-RADS 5th edition revealed a higher proportion of dense breast than assessment using BI-RADS 4th edition. Nevertheless, automated volumetric density assessment had good correlation with visual assessment for both editions of BI-RADS.

  11. Successful 4th kidney transplantation: a case report from Iran.

    PubMed

    Nourbala, Mohammad Hossein; Ghadian, Alireza; Einollahi, Behzad; Azarabadi, Mehdi

    2013-05-21

    Kidney transplantation is generally considered the best option for most patients with end-stage renal disease requiring renal replacement therapy, even for patients with graft failure. Here, we describe a case of a 49-year-old man who received his 1st kidney transplant the United Kingdom from his brother when he was 18 years old in. Thirty-one year after the first transplant, he underwent successful 4th living-unrelated kidney transplantation with no serious complications at our transplant center. He continued to have excellent allograft function and his latest serum creatinine 33 months after his 4th transplant was 1.2 mg/dL. To our knowledge, this is the first case of 4th kidney transplantation from Iran.

  12. Relationships between Grade Levels, Personal Factors, and Instructional Variation among 4th-12th Grade Teachers

    ERIC Educational Resources Information Center

    White, Jacquelyn M.

    2011-01-01

    The purpose of this quantitative correlational study was to investigate relationships between grade levels, personal factors of teachers, and instructional variety used by 4th-12th grade teachers in Kern County, California. The population under investigation included 2,844 teachers. 235 elementary, middle school/junior high, and secondary teachers…

  13. 75 FR 34636 - Safety Zone; Jameson Beach 4th of July Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ...-AA00 Safety Zone; Jameson Beach 4th of July Fireworks Display AGENCY: Coast Guard, DHS. ACTION... waters of Lake Tahoe, for the Jameson Beach 4th of July Fireworks Display. This safety zone is... Safety Zone; Jameson Beach 4th of July Fireworks Display. (a) Location. This temporary safety zone is...

  14. 4TH Marine Division Operation Plan Number 49-44

    DTIC Science & Technology

    1944-12-26

    information if it does not display a currently valid OMB control number. 1. REPORT DATE MAY 1972 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND...assigned (Annex DOG to Adm 0 No. ;44-44,. (2) 4th Tk Bn (less Cos A, B, & C), on landing, be prepared to assume control of Tk Elms as released and Spt...the Atk. (3) 41th Ned Bn, on landing Bn Ho and on Div order, assume control of Cos A, B, and C ashore, prepared to land the remainder of the Bn on Div

  15. Bathymetry and Near-River Topography of the Naches and Yakima Rivers at Union Gap and Selah Gap, Yakima County, Washington, August 2008

    USGS Publications Warehouse

    Mastin, M.C.; Fosness, R.L.

    2009-01-01

    Yakima County is collaborating with the Bureau of Reclamation on a study of the hydraulics and sediment-transport in the lower Naches River and in the Yakima River between Union Gap and Selah Gap in Washington. River bathymetry and topographic data of the river channels are needed for the study to construct hydraulic models. River survey data were available for most of the study area, but river bathymetry and near-river topography were not available for Selah Gap, near the confluence of the Naches and Yakima Rivers, and for Union Gap. In August 2008, the U.S. Geological Survey surveyed the areas where data were not available. If possible, the surveys were made with a boat-mounted, single-beam echo sounder attached to a survey-grade Real-Time Kinematic (RTK) global positioning system (GPS). An RTK GPS rover was used on a walking survey of the river banks, shallow river areas, and river bed areas that were impenetrable to the echo sounder because of high densities of macrophytes. After the data were edited, 95,654 bathymetric points from the boat survey with the echo sounder and 1,069 points from the walking survey with the GPS rover were used in the study. The points covered 4.6 kilometers on the Yakima River and 0.6 kilometers on the Naches River. GPS-surveyed points checked within 0.014 to 0.047 meters in the horizontal direction and -0.036 to 0.078 meters in the vertical direction compared to previously established survey control points

  16. 76 FR 37649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS... annual July 4th Fireworks Display (Tahoe City 4th of July Fireworks Display). This action is necessary to... INFORMATION: The Coast Guard will enforce the safety zone for the annual Tahoe City 4th of July Fireworks in...

  17. Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

    PubMed

    Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

    1986-03-01

    Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

  18. Structure of MyTH4-FERM domains in myosin VIIa tail bound to cargo.

    PubMed

    Wu, Lin; Pan, Lifeng; Wei, Zhiyi; Zhang, Mingjie

    2011-02-11

    The unconventional myosin VIIa (MYO7A) is one of the five proteins that form a network of complexes involved in formation of stereocilia. Defects in these proteins cause syndromic deaf-blindness in humans [Usher syndrome I (USH1)]. Many disease-causing mutations occur in myosin tail homology 4-protein 4.1, ezrin, radixin, moesin (MyTH4-FERM) domains in the myosin tail that binds to another USH1 protein, Sans. We report the crystal structure of MYO7A MyTH4-FERM domains in complex with the central domain (CEN) of Sans at 2.8 angstrom resolution. The MyTH4 and FERM domains form an integral structural and functional supramodule binding to two highly conserved segments (CEN1 and 2) of Sans. The MyTH4-FERM/CEN complex structure provides mechanistic explanations for known deafness-causing mutations in MYO7A MyTH4-FERM. The structure will also facilitate mechanistic and functional studies of MyTH4-FERM domains in other myosins.

  19. 75 FR 34639 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ...-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA AGENCY: Coast Guard... Cockrell's Creek in the vicinity of Reedville, Virginia in support of the Reedville July 4th Celebration... notice of proposed rulemaking (NPRM) entitled Reedville July 4th Celebration, Cockrell's Creek, Reedville...

  20. 4. LOOKING NORTHEAST TOWARDS LOCKS. 19TH CENTURY GRAVITY LOCKS ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. LOOKING NORTHEAST TOWARDS LOCKS. 19TH CENTURY GRAVITY LOCKS ON RIGHT. 20TH CENTURY ELECTRIC LIFT LOCKS ON LEFT. - New York State Barge Canal, Lockport Locks, Richmond Avenue, Lockport, Niagara County, NY

  1. 75 FR 26157 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ...-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA AGENCY: Coast Guard... Reedville July 4th Celebration event. This action is intended to restrict vessel traffic movement on... established in the interest of public safety during the Reedville July 4th Celebration event and will be...

  2. Color duplex assessment of 4th and 5th internal mammary artery perforators: the pedicles of the medially based lower pole breast flaps.

    PubMed

    Abdel-Monem, Kareem; Elshahat, Ahmed; Abou-Gamrah, Sherif; Eldin Abol-Atta, Hossam; Abd Eltawab, Reda; Massoud, Karim

    2012-01-01

    Reconstruction of a breast after mastectomy using the contralateral lower pole breast flap is an appealing procedure because it uses the tissues that were going to be excised during reduction of the sound breast to achieve symmetry. Literature mentioned that these flaps are supplied by the lower internal mammary artery perforators (IMAPs) with no further details. The aim of this study was to determine the site, size, and number of the 4th and 5th IMAPs by using preoperative color Duplex ultrasound and intraoperative exploration. Twenty breasts in 10 patients who presented for reduction mammoplasty were included in this study. Preoperative color duplex was used to determine IMAPs in the 4th and 5th intercostal spaces. These perforators were localized intraoperatively. Intravenous fluorescein injection was used to determine the perfusion of the lower pole breast flap on the basis of these perforators. Statistically, the 4th IMAPs diameters were significantly larger than the 5th IMAPs diameters (P < .05). The lower pole breast flap was perfused through these perforators. Color Duplex ultrasound is an accurate tool to preoperatively determine the 4th and 5th IMAPs.

  3. Color Duplex Assessment of 4th and 5th Internal Mammary Artery Perforators: The Pedicles of the Medially Based Lower Pole Breast Flaps

    PubMed Central

    Abdel-Monem, Kareem; Elshahat, Ahmed; Abou-Gamrah, Sherif; Eldin Abol-Atta, Hossam; Abd Eltawab, Reda; Massoud, Karim

    2012-01-01

    Objective: Reconstruction of a breast after mastectomy using the contralateral lower pole breast flap is an appealing procedure because it uses the tissues that were going to be excised during reduction of the sound breast to achieve symmetry. Literature mentioned that these flaps are supplied by the lower internal mammary artery perforators (IMAPs) with no further details. The aim of this study was to determine the site, size, and number of the 4th and 5th IMAPs by using preoperative color Duplex ultrasound and intraoperative exploration. Method: Twenty breasts in 10 patients who presented for reduction mammoplasty were included in this study. Preoperative color duplex was used to determine IMAPs in the 4th and 5th intercostal spaces. These perforators were localized intraoperatively. Intravenous fluorescein injection was used to determine the perfusion of the lower pole breast flap on the basis of these perforators. Results: Statistically, the 4th IMAPs diameters were significantly larger than the 5th IMAPs diameters (P < .05). The lower pole breast flap was perfused through these perforators. Conclusion: Color Duplex ultrasound is an accurate tool to preoperatively determine the 4th and 5th IMAPs. PMID:22292100

  4. Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

    PubMed

    Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

    2013-08-01

    Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p < 0.05). Histological parameters, such as crypt depth and villus height, were also significantly decreased by doxorubicin. TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

  5. 16. 4th floor roof, view west, north side of setback ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. 4th floor roof, view west, north side of setback to left and delivery stair bulkhead to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  6. Thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system

    NASA Astrophysics Data System (ADS)

    Capelli, E.; Beneš, O.; Konings, R. J. M.

    2014-06-01

    The present study describes the full thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system which is one of the key systems considered for a molten salt reactor fuel. The work is an extension of the previously assessed LiF-NaF-ThF4-UF4 system with addition of BeF2 which is characterized by very low neutron capture cross section and a relatively low melting point. To extend the database the binary BeF2-ThF4 and BeF2-UF4 systems were optimized and the novel data were used for the thermodynamic assessment of BeF2 containing ternary systems for which experimental data exist in the literature. The obtained database is used to optimize the molten salt reactor fuel composition and to assess its properties with the emphasis on the melting behaviour.

  7. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Safety Zone: Macy's July 4th... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area.... on July 4th. If the event is cancelled due to inclement weather then this section is in effect from 6...

  8. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety Zone: Macy's July 4th... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area.... on July 4th. If the event is cancelled due to inclement weather then this section is in effect from 6...

  9. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Safety Zone: Macy's July 4th... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area.... on July 4th. If the event is cancelled due to inclement weather then this section is in effect from 6...

  10. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Safety Zone: Macy's July 4th... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area.... on July 4th. If the event is cancelled due to inclement weather then this section is in effect from 6...

  11. Kids & Family Reading Report™. 4th Edition

    ERIC Educational Resources Information Center

    Scholastic Inc., 2013

    2013-01-01

    This report presents the 4th Edition of Scholastic's biannual study of children's and parents' attitudes and behaviors about reading. Much has changed since the first "Kids & Family Reading Report" was issued in 2006, but literacy remains the critical skill needed for school success. Today's children are growing up in a world full of…

  12. Modeling of Synergy Between 4th and 6th Harmonic Absorptions of Fast Waves on Injected Beams in DIII-D Tokamak

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choi, M.; Pinsker, R. I.; Chan, V. S.

    2011-12-23

    In recent moderate to high harmonic fast wave heating and current drive experiments in DIII-D, a synergy effect was observed when the 6{sup th} harmonic 90 MHz fast wave power is applied to the plasma preheated by neutral beams and the 4{sup th} harmonic 60 MHz fast wave. In this paper, we investigate how the synergy can occur using ORBIT-RF coupled with AORSA. Preliminary simulations suggest that damping of 4{sup th} harmonic FW on beam ions accelerates them above the injection energy, which may allow significant damping of 6{sup th} harmonic FW on beam ion tails to produce synergy.

  13. Impacts of a Discussion-Based Academic Language Program on Classroom Interactions in 4th through 7th Grades

    ERIC Educational Resources Information Center

    LaRusso, Maria; Jones, Stephanie M.; Kim, Ha Yeon; Kim, James; Donovan, Suzanne; Snow, Catherine

    2016-01-01

    This paper presents an exploratory analysis of treatment-control differences in the quality of classroom interactions in 4th through 7th grade urban classrooms. Word Generation (WG) is a research-based academic language program for middle school students designed to teach novel vocabulary and literacy through language arts, math, science, and…

  14. The risk of a second diagnostic window with 4th generation HIV assays: Two cases.

    PubMed

    Niederhauser, C; Ströhle, A; Stolz, M; Müller, F; Tinguely, C

    2009-08-01

    Despite the improved sensitivity of the 4th generation combined antigen/antibody HIV assays, detection of HIV in the early phase of an infection may still be ineffective. Description of two cases that highlight the existence of the "second diagnostic window phase" observed with commonly used sensitive 4th generation HIV assays. Samples were screened with different 4th generation HIV assays. HIV infection was confirmed with an HIV I/II antibody assay, a HIV-1 p24 antigen assay, the INNO-LIA HIV I/II Score Line immunoassay and HIV-1 PCR. In both investigated cases, the limitations of the 4th generation HIV assays within the second diagnostic window were apparent. The overall sensitivity of the commercial 4th generation HIV assays is currently higher than the 3rd generation HIV assays. Nevertheless, the rare occurrence of a second diagnostic window with 4th generation HIV assays strongly suggests that the following up testing algorithms need to be adjusted accordingly.

  15. 75 FR 35649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce the Tahoe City 4th of... safety zone for the annual Tahoe City 4th of July Fireworks in 33 CFR 165.1191 on July 4, 2010, from 9 a...

  16. Preliminary Study on LiF4-ThF4-PuF4 Utilization as Fuel Salt of miniFUJI Molten Salt Reactor

    NASA Astrophysics Data System (ADS)

    Waris, Abdul; Aji, Indarta K.; Pramuditya, Syeilendra; Widayani; Irwanto, Dwi

    2016-08-01

    miniFUJI reactor is molten salt reactor (MSR) which is one type of the Generation IV nuclear energy systems. The original miniFUJI reactor design uses LiF-BeF2-ThF4-233UF4 as a fuel salt. In the present study, the use of LiF4-ThF4-PuF4 as fuel salt instead of LiF-BeF2-ThF4-UF4 will be discussed. The neutronics cell calculation has been performed by using PIJ (collision probability method code) routine of SRAC 2006 code, with the nuclear data library is JENDL-4.0. The results reveal that the reactor can attain the criticality condition with the plutonium concentration in the fuel salt is equal to 9.16% or more. The conversion ratio diminishes with the enlarging of plutonium concentration in the fuel. The neutron spectrum of miniFUJI MSR with plutonium fuel becomes harder compared to that of the 233U fuel.

  17. HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells

    PubMed Central

    Araya, Natsumi; Sato, Tomoo; Ando, Hitoshi; Tomaru, Utano; Yoshida, Mari; Coler-Reilly, Ariella; Yagishita, Naoko; Yamauchi, Junji; Hasegawa, Atsuhiko; Kannagi, Mari; Hasegawa, Yasuhiro; Takahashi, Katsunori; Kunitomo, Yasuo; Tanaka, Yuetsu; Nakajima, Toshihiro; Nishioka, Kusuki; Utsunomiya, Atae; Jacobson, Steven; Yamano, Yoshihisa

    2014-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is linked to multiple diseases, including the neuroinflammatory disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. Evidence suggests that HTLV-1, via the viral protein Tax, exploits CD4+ T cell plasticity and induces transcriptional changes in infected T cells that cause suppressive CD4+CD25+CCR4+ Tregs to lose expression of the transcription factor FOXP3 and produce IFN-γ, thus promoting inflammation. We hypothesized that transformation of HTLV-1–infected CCR4+ T cells into Th1-like cells plays a key role in the pathogenesis of HAM/TSP. Here, using patient cells and cell lines, we demonstrated that Tax, in cooperation with specificity protein 1 (Sp1), boosts expression of the Th1 master regulator T box transcription factor (T-bet) and consequently promotes production of IFN-γ. Evaluation of CSF and spinal cord lesions of HAM/TSP patients revealed the presence of abundant CD4+CCR4+ T cells that coexpressed the Th1 marker CXCR3 and produced T-bet and IFN-γ. Finally, treatment of isolated PBMCs and CNS cells from HAM/TSP patients with an antibody that targets CCR4+ T cells and induces cytotoxicity in these cells reduced both viral load and IFN-γ production, which suggests that targeting CCR4+ T cells may be a viable treatment option for HAM/TSP. PMID:24960164

  18. Activation of CH4 by Th(+) as studied by guided ion beam mass spectrometry and quantum chemistry.

    PubMed

    Cox, Richard M; Armentrout, P B; de Jong, Wibe A

    2015-04-06

    The reaction of atomic thorium cations with CH4 (CD4) and the collision-induced dissociation (CID) of ThCH4(+) with Xe are studied using guided ion beam tandem mass spectrometry. In the methane reactions at low energies, ThCH2(+) (ThCD2(+)) is the only product; however, the energy dependence of the cross-section is inconsistent with a barrierless exothermic reaction as previously assumed on the basis of ion cyclotron resonance mass spectrometry results. The dominant product at higher energies is ThH(+) (ThD(+)), with ThCH3(+) (ThCD3(+)) having a similar threshold energy. The latter product subsequently decomposes at still higher energies to ThCH(+) (ThCD(+)). CID of ThCH4(+) yields atomic Th(+) as the exclusive product. The cross-sections of all product ions are modeled to provide 0 K bond dissociation energies (in eV) of D0(Th(+)-H) ≥ 2.25 ± 0.18, D0(Th(+)-CH) = 6.19 ± 0.16, D0(Th(+)-CH2) ≥ 4.54 ± 0.09, D0(Th(+)-CH3) = 2.60 ± 0.30, and D0(Th(+)-CH4) = 0.47 ± 0.05. Quantum chemical calculations at several levels of theory are used to explore the potential energy surfaces for activation of methane by Th(+), and the effects of spin-orbit coupling are carefully considered. When spin-orbit coupling is explicitly considered, a barrier for C-H bond activation that is consistent with the threshold measured for ThCH2(+) formation (0.17 ± 0.02 eV) is found at all levels of theory, whereas this barrier is observed only at the BHLYP and CCSD(T) levels otherwise. The observation that the CID of the ThCH4(+) complex produces Th(+) as the only product with a threshold of 0.47 eV indicates that this species has a Th(+)(CH4) structure, which is also consistent with a barrier for C-H bond activation. This barrier is thought to exist as a result of the mixed ((4)F,(2)D) electronic character of the Th(+) J = (3)/2 ground level combined with extensive spin-orbit effects.

  19. 77 FR 40266 - Safety Zone; Conneaut 4th of July Festival, Lake Erie, Conneaut, OH

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... 1625-AA00 Safety Zone; Conneaut 4th of July Festival, Lake Erie, Conneaut, OH AGENCY: Coast Guard, DHS... the Conneaut 4th of July Festival Fireworks display. This temporary safety zone is necessary to... vessels during the Conneaut 4th of July Festival Fireworks. This zone will be effective and enforced from...

  20. Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.

    PubMed

    Johansson, Anna-Mia; Stenberg, Per; Bernhardsson, Carolina; Larsson, Jan

    2007-05-02

    Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

  1. Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster

    PubMed Central

    Johansson, Anna-Mia; Stenberg, Per; Bernhardsson, Carolina; Larsson, Jan

    2007-01-01

    Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome. PMID:17318176

  2. 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

    PubMed

    Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

    2016-03-15

    4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. Copyright © 2016. Published by Elsevier Ltd.

  3. 77 FR 39172 - Safety Zone: Skagway Harbor, Skagway, AK for 4th of July Fireworks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ...-AA00 Safety Zone: Skagway Harbor, Skagway, AK for 4th of July Fireworks AGENCY: Coast Guard, DHS... of the Small Boat Harbor, Skagway, Alaska, to limit access for the duration of the 4th of July... Inlet for the City of Skagway, Alaska, sponsored 4th of July fireworks display. A no-action alternative...

  4. Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia

    PubMed Central

    Saito, S; Sakai, M; Sasaki, Y; Tanebe, K; Tsuda, H; Michimata, T

    1999-01-01

    We calculated the percentage of Th1, Th2, Th0 cells and the Th1:Th2 cell ratio of peripheral blood from normal pregnant subjects and preeclampsia patients using flow cytometry which can analyse both the surface marker, CD4, and intracellular cytokines, interleukin (IL)-4 and interferon (IFN)-γ. In normal pregnancy, the percentage of Th1 cells was significantly lower in the third trimester, and the ratios of Th1:Th2 were significantly lower in the second and third trimester than in nonpregnant subjects. In contrast, the percentage of Th1 cells and the ratios of Th1:Th2 in preeclampsia were significantly higher than in normal third trimester pregnant subjects. The percentage of Th2 cells in preeclampsia was significantly lower than in third trimester of normal pregnancy. Additionally, peripheral blood mononuclear cells from these subjects and patients were cultured with phytohemagglutinin stimulation, and IL-4 and IFN-γ concentrations were determined in the supernatant by enzymed linked immunosorbent assays. The percentage of Th1 and Th2, and the ratios of Th1:Th2 were correlated with cytokine (IFN-γ and IL-4) secretion level. These results demonstrated that Th2 cells were predominant in the second and third trimesters of normal pregnancy, but Th1 cells predominated in preeclamptic patients. PMID:10469061

  5. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models.

    PubMed

    Chen, Q; Muramoto, K; Masaaki, N; Ding, Y; Yang, H; Mackey, M; Li, W; Inoue, Y; Ackermann, K; Shirota, H; Matsumoto, I; Spyvee, M; Schiller, S; Sumida, T; Gusovsky, F; Lamphier, M

    2010-05-01

    Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E(2) (PGE(2)) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE(2) EP(4) receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. Effects of PGE(2) and a novel EP(4) receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. Stimulation of the EP(4) receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE(2) antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen- and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. PGE(2) stimulates EP(4) receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP(4) receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.

  6. Watershed scale response to climate change--Naches River Basin, Washington

    USGS Publications Warehouse

    Mastin, Mark C.; Hay, Lauren E.; Markstrom, Steven L.

    2012-01-01

    Fourteen basins for which the Precipitation Runoff Modeling System has been calibrated and evaluated were selected as study sites. Precipitation Runoff Modeling System is a deterministic, distributed parameter watershed model developed to evaluate the effects of various combinations of precipitation, temperature, and land use on streamflow and general basin hydrology. Output from five General Circulation Model simulations and four emission scenarios were used to develop an ensemble of climate-change scenarios for each basin. These ensembles were simulated with the corresponding Precipitation Runoff Modeling System model. This fact sheet summarizes the hydrologic effect and sensitivity of the Precipitation Runoff Modeling System simulations to climate change for the Naches River Basin below Tieton River in Washington.

  7. 11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, WITH WRAPPER (LEFT), PRESS (CENTER), AND CUTTER (RIGHT, BEHIND CHUTE); BUCKET CONVEYOR AT RIGHT MOVED WASTE FROM PRESS TO 5TH FLOOR FOR RE-MANUFACTURE - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  8. Guanine nucleotide-binding protein α subunit hypofunction in children with short stature and disproportionate shortening of the 4th and 5th metacarpals.

    PubMed

    Inta, Ioana Monica; Choukair, Daniela; Bender, Sebastian; Kneppo, Carolin; Knauer-Fischer, Sabine; Meyenburg, Kahina; Ivandic, Boris; Pfister, Stefan M; Bettendorf, Markus

    2014-01-01

    GNAS encodes the α subunit of the stimulatory G protein (Gsα). Maternal inherited Gsα mutations cause pseudohypoparathyroidism type Ia (PHP-Ia), associated with shortening of the 4th and 5th metacarpals. Here we investigated the Gsα pathway in short patients with distinct shortening of the 4th and 5th metacarpals. In 571 children with short stature and 4 patients with PHP-Ia metacarpal bone lengths were measured. In identified patients we analysed the Gsα protein function in platelets, performed GNAS sequencing, and epigenetic analysis of four significant differentially methylated regions. In 51 patients (8.9%) shortening of the 4th and 5th metacarpals was more pronounced than their height deficit. No GNAS coding mutations were identified in 20 analysed patients, except in 2 PHP-Ia patients. Gsα activity was reduced in all PHP-Ia patients and in 25% of the analysed patients. No significant methylation changes were identified. Our findings suggest that patients with short stature and distinct metacarpal bone shortening could be part of the wide variety of PHP/PPHP, therefore it was worthwhile analysing the Gsα protein function and GNAS gene in these patients in order to further elucidate the phenotype and genotype of Gsα dysfunction.

  9. Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- and Th2-type CD4+ T cells in mice.

    PubMed

    Zeis, M; Uharek, L; Hartung, G; Glass, B; Steinmann, J; Schmitz, N

    2001-01-01

    The transfer of allogeneic lymphocytes contained in a hematopoietic stem cell graft confers an immune-mediated antileukemic effect, termed the graft-vs-leukemia (GVL) effect. Graft-vs-host disease (GVHD), the most detrimental complication of allogeneic BMT, largely resides within the same lymphocyte population. Therefore, separation of GVL- and GVH-reactions is a long-standing goal of experimental studies dealing with allogeneic transplantation of hematopoietic stem cells. The objective of the current study was to assess the potential of Th1- and Th2-type CD4+ T cells in mediating GVHD and GVL effects in a fully allogeneic murine transplant model. BALB/c (H-2d) mice were given a dose of A20 (H-2d, B-cell leukemia) cells two days prior to lethal total body irradiation (TBI) and transplantation of fully mismatched (C57BL/6, H-2b) T-cell depleted (anti-Thy1.2, CD90) bone marrow (TCD-BM) cells. Graded numbers of either unmanipulated, Th1- or Th2-polarized highly enriched CD4+ donor type T cells (10(6) or 10(7)) were administered 2 h posttransplant. Infusion of 10(6) of unmanipulated, Th1-, or Th2-primed CD4+ T cells resulted in moderate GVHD-related mortality (40%, 50%, 10%) and significantly improved long-term survival (50%, 45%, 46% surviving the observation period of 120 days) as compared to animals receiving TCD-BM alone (18%). The administration of 10(7) unmanipulated or Th1-type CD4+ T cells given shortly after transplantation led to death of all mice within 50 days due to fatal acute GVHD. In contrast, the adoptive transfer of 10(7) Th2-primed CD4+ T cells resulted in significant improvement of long-term survival (80%) compared to the TCD-BM group. This powerful GVL effect was associated with a substantially lower incidence of lethal acute GVHD (10%) if compared to the results of transplantation of Th1-type CD4+ T cells. These results demonstrate that allogeneic Th2-type CD4+ T cells given post BMT can induce GVL effects in a cell-dose-dependent manner without

  10. Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4+ T cell activation.

    PubMed

    Carrión, Flavio; Nova, Estefania; Luz, Patricia; Apablaza, Felipe; Figueroa, Fernando

    2011-03-30

    Mesenchymal stem cells (MSCs) are multipotent progenitors with broad immunosuppressive properties. However, their therapeutic use in autoimmune disease models has shown dissimilar effects when applied at different stages of disease. We therefore investigated the effect of the addition of MSCs on the differentiation of Th1, Treg and Th17 cells in vitro, at different states of CD4(+) T cell activation. CD4(+) T lymphocytes purified by negative selection from mouse C57BL/6 splenocytes were cultured under Th1, Th17 and Treg inducing conditions with IL-12, TGF-β+IL-6 or TGF-β, respectively. C57BL/6 bone marrow derived MSCs were added to CD4(+) T cell cultures at day 0 or after 3 days of T cell polarizing activation. Intracellular cytokines for Th1, Th17 and Treg cells were quantitated at day 6 by flow cytometry. While early addition (day 0) of MSCs suppressed all CD4(+) T cell lineages, addition at day 3 only decreased IFN-γ production by Th1 polarized cells by 64% (p<0.05) while markedly increased IL-17 production by Th17 polarized cells by 50% (p<0.05) and left IL-10 production by Treg polarized cells unchanged. MSCs exhibit their typical suppressive phenotype when added early to cell cultures in the presence of CD4(+) T cell polarizing stimuli. However, once T cell activation has occurred, MSCs show an opposite stimulating effect on Th17 cells, while leaving Treg IL-10 producing cells unchanged. These results suggest that the therapeutic use of MSCs in vivo might exert opposing effects on disease activity, according to the time of therapeutic application and the level of effector T cell activation. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. 76 FR 37650 - Safety Zone; 4th of July Festival Berkeley Marina Fireworks Display Berkeley, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ...-AA00 Safety Zone; 4th of July Festival Berkeley Marina Fireworks Display Berkeley, CA AGENCY: Coast... the 4th of July Festival Berkeley Marina Fireworks Display. Unauthorized persons or vessels are... display. Background and Purpose The City of Berkeley Marina will sponsor the 4th of July Festival Berkeley...

  12. Upregulation of bacterial-specific Th1 and Th17 responses that are enriched in CXCR5+CD4+ T cells in non-small cell lung cancer.

    PubMed

    Ma, Qin-Yun; Huang, Da-Yu; Zhang, Hui-Jun; Wang, Shaohua; Chen, Xiao-Feng

    2017-11-01

    The microbial community in the mucosal surfaces is involved in the development of human cancers, including gastric cancer and colorectal cancer. The respiratory tract in the lung also hosts a distinctive microbial community, but the correlation between this community and lung cancer is largely unknown. Here, we examined the Th1 and Th17 responses toward several bacterial antigens, in CD4 + T cells sourced from the peripheral blood (PB), the lung cancer (LC) tissue, and the gastrointestinal (GI) tract of non-small cell lung cancer (NSCLC) patients. Compared to healthy controls, the NSCLC patients presented significantly higher frequencies of Th1 and Th17 cells reacting to Streptococcus salivarius and S. agalactiae, in the PB, LC, and GI tract. Further investigation showed that the upregulation in anti-bacteria response was likely antigen-specific for two reasons. Firstly, the frequencies of Th1 and Th17 cells reacting to Escherichia coli, a typical GI bacterium, were not upregulated in the PB and the LC of NSCLC patients. Secondly, the S. salivarius and S. agalactiae responses could be partially blocked by Tü39, a MHC class II blocking antibody, suggesting that antigen-specific interaction between CD4 + T cells and antigen-presenting cells was required. We also found that S. salivarius and S. agalactiae could potently activate the monocytes to secrete higher levels of interleukin (IL)-6, IL-12, and tumor necrosis factor, which were Th1- and Th17-skewing cytokines. Interestingly, whereas CXCR5 + CD4 + T cells represented <20% of total CD4 + T cells, they represented 17%-82% of bacteria-specific Th1 or Th17 cells. Together, these data demonstrated that NSCLC patients presented a significant upregulation of bacterial-specific Th1 and Th17 responses that were enriched in CXCR5 + CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Collaborative study for the establishment of the 4(th) International Standard for Streptomycin.

    PubMed

    Jorajuria, S; Raphalen, C; Dujardin, V; Daas, A

    2015-01-01

    An international collaborative study was organised to establish the 4(th) World Health Organization (WHO) International Standard (IS) for Streptomycin. Fourteen laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms. To ensure continuity between consecutive batches, the 3(rd) IS for Streptomycin was used as a reference. Based on the results of the study, the 4(th) IS for Streptomycin was adopted at the meeting of the WHO Expert Committee for Biological Standardization (ECBS) in 2015 with an assigned potency of 76 000 International Units (IU) per vial. The 4(th) IS for Streptomycin is available from the European Directorate for the Quality of Medicines & HealthCare (EDQM).

  14. 77 FR 30242 - Safety Zone; City of Tonawanda July 4th Celebration, Niagara River, Tonawanda, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ...-AA00 Safety Zone; City of Tonawanda July 4th Celebration, Niagara River, Tonawanda, NY AGENCY: Coast... vessels from a portion of the Niagara River during the City of Tonawanda July 4th Celebration fireworks... read as follows: Sec. 165.T09-0352 Safety Zone; City of Tonawanda July 4th Celebration, Niagara River...

  15. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

    ERIC Educational Resources Information Center

    Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

    2016-01-01

    Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered…

  16. ThMYC4E, candidate Blue aleurone 1 gene controlling the associated trait in Triticum aestivum

    PubMed Central

    Chen, Wenjie; Zhang, Bo; Wang, Daowen; Liu, Dengcai; Zhang, Huaigang

    2017-01-01

    Blue aleurone is a useful and interesting trait in common wheat that was derived from related species. Here, transcriptomes of blue and white aleurone were compared for isolating Blue aleurone 1 (Ba1) transferred from Thinopyrum ponticum. In the genes involved in anthocyanin biosynthesis, only a basic helix-loop-helix (bHLH) transcription factor, ThMYC4E, had a higher transcript level in blue aleurone phenotype, and was homologous to the genes on chromosome 4 of Triticum aestivum. ThMYC4E carried the characteristic domains (bHLH-MYC_N, HLH and ACT-like) of a bHLH transcription factor, and clustered with genes regulating anthocyanin biosynthesis upon phylogenetic analysis. The over-expression of ThMYC4E regulated anthocyanin biosynthesis with the coexpression of the MYB transcription factor ZmC1 from maize. ThMYC4E existed in the genomes of the addition, substitution and near isogenic lines with the blue aleurone trait derived from Th. ponticum, and could not be detected in any germplasm of T. urartu, T. monococcum, T. turgidum, Aegilops tauschii or T. aestivum, with white aleurone. These results suggested that ThMYC4E was candidate Ba1 gene controlling the blue aleurone trait in T. aestivum genotypes carrying Th. ponticum introgression. The ThMYC4E isolation aids in better understanding the genetic mechanisms of the blue aleurone trait and in its more effective use during wheat breeding. PMID:28704468

  17. Native American Students' Understanding of Geologic Time Scale: 4th-8th Grade Ojibwe Students' Understanding of Earth's Geologic History

    ERIC Educational Resources Information Center

    Nam, Younkyeong; Karahan, Engin; Roehrig, Gillian

    2016-01-01

    Geologic time scale is a very important concept for understanding long-term earth system events such as climate change. This study examines forty-three 4th-8th grade Native American--particularly Ojibwe tribe--students' understanding of relative ordering and absolute time of Earth's significant geological and biological events. This study also…

  18. 75 FR 38721 - Safety Zone; Munising 4th of July Fireworks, South Bay, Lake Superior, Munising, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ...-AA00 Safety Zone; Munising 4th of July Fireworks, South Bay, Lake Superior, Munising, MI AGENCY: Coast... portion of South Bay during the Munising 4th of July Fireworks display, July 4, 2010. This temporary... from hazards associated with the Munising 4th of July Fireworks display. Based on the explosive hazards...

  19. 75 FR 34379 - Safety Zone; Mackinac Island 4th of July Fireworks, Lake Huron, Mackinac Island, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ...-AA00 Safety Zone; Mackinac Island 4th of July Fireworks, Lake Huron, Mackinac Island, MI AGENCY: Coast... of Lake Huron during the Mackinac Island 4th of July Fireworks display on July 4, 2010. This... and vessels during the setup, and launching of fireworks in conjunction with the Mackinac Island 4th...

  20. 10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, WITH AUTOMATIC CUTTER (LEFT), PRESS (CENTER), AND WRAPPER (RIGHT); LARGE CHUTE AT CENTER FROM 5TH FLOOR BINS TO 3RD FLOOR SOAP MILLS; OVERHEAD AND FLOOR (LOWER RIGHT) FINISHED GOODS CONVEYORS TO G BLOCK (HAER NO. NJ-71-NN) - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  1. Th(As(III)4As(V)4O18): a mixed-valent oxoarsenic(III)/arsenic(V) actinide compound obtained under extreme conditions.

    PubMed

    Yu, Na; Klepov, Vladislav V; Kegler, Philip; Bosbach, Dirk; Albrecht-Schmitt, Thomas E; Alekseev, Evgeny V

    2014-08-18

    A high-temperature/high-pressure method was employed to investigate phase formation in the Th(NO3)4·5H2O-As2O3-CsNO3 system. It was observed that an excess of arsenic(III) in starting system leads to the formation of Th(As(III)4As(V)4O18), which is representative of a rare class of mixed-valent arsenic(III)/arsenic(V) compounds. This compound was studied with X-ray diffraction, energy-dispersive X-ray, and Raman spectroscopy methods. Crystallographic data show that Th(As(III)4As(V)4O18) is built from (As(III)4As(V)4O18)(4-) layers connected through Th atoms. The arsenic layers are found to be isoreticular to those in previously reported As2O3 and As3O5(OH), and the geometric differences between them are discussed. Bands in the Raman spectrum are assigned with respect to the presence of AsO3 and AsO4 groups.

  2. The school nutrition program's role in weight management of 4th grade elementary students

    USDA-ARS?s Scientific Manuscript database

    We are attempting to uncover the school nutrition program's role in weight management of 4th grade elementary students. Data was collected within a time frame for the food frequency questionnaire (FFQ) set at two months at the WT Cheney Elementary School and South Wood Elementary for 4th grade stud...

  3. 75 FR 35294 - Safety Zone; Marquette 4th of July Fireworks, Marquette Harbor, Lake Superior, Marquette, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ...-AA00 Safety Zone; Marquette 4th of July Fireworks, Marquette Harbor, Lake Superior, Marquette, MI... vessels from a portion of Marquette Harbor during the Marquette 4th of July Fireworks display. This... vessels during the setup and launching of fireworks in conjunction with the Marquette 4th of July...

  4. 11(th) National Meeting of Organic Chemistry and 4(th) Meeting of Therapeutic Chemistry.

    PubMed

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho E Melo, Teresa M V D; Freitas, Victor

    2016-03-17

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report.

  5. [A development of Byzantine Christian charities during the 4(th)-7(th) centuries and the birth of the hospital].

    PubMed

    Nam, Sung Hyun

    2015-04-01

    This study aims to examine the beginning and the development of Christian Charities during the 4(th)-6(th) centuries which would eventually result in the birth of the hospital in modern sense in the first half of the 7(th) century. For this purpose, I looked carefully into various primary sources concerning the early Christian institutions for the poor and the sick. Above all, it's proper to note that the first xenodocheion where hospitality was combined with a systematic caring, is concerned with the Trinitarian debate of the 4(th) century. In 356, Eustathios, one of the leaders of homoiousios group, established xenodocheion to care for the sick and the lepers in Sebaste of Armenia, whereas his opponent Aetios, doctor and leader of the heteroousios party, was reckoned to have combined the medical treatment with his clerical activities. Then, Basil of Caesarea, disciple of Eustathios of Sebaste, also founded in 372 a magnificent benevolent complex named 'Basileias' after its founder. I scrupulously analysed several contemporary materials mentioning the charitable institution of Caesarea which was called alternatively katagogia, ptochotropheion, xenodocheion. John Chrysostome also founded several nosokomeia in Constantinople at the end of the 4(th) century and the beginning of the 5(th) century. Apparently, the contemporary sources mention that doctors existed for these Charities, but there is no sufficient proof that these 'Christian Hospitals,' Basileias or nosokomeia of Constantinople were hospitals in modern sense. Imperial constitutions began to mention ptochotropheion, xenodocheion and orphanotropheion since the second half of the 5(th) century and then some Justinian laws evoked nosokomium, brephotrophia, gerontocomia. These laws reveal that 'Christian Hospitals' were well clarified and deeply rooted in Byzantine society already in these periods. And then, new benevolent institutions emerged in the 6(th) century: nosokomeia for a specific class and

  6. Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells.

    PubMed

    Luz-Crawford, Patricia; Kurte, Monica; Bravo-Alegría, Javiera; Contreras, Rafael; Nova-Lamperti, Estefania; Tejedor, Gautier; Noël, Danièle; Jorgensen, Christian; Figueroa, Fernando; Djouad, Farida; Carrión, Flavio

    2013-06-04

    Mesenchymal stem cells (MSCs) are adult, multipotent, stem cells with immunomodulatory properties. The mechanisms involved in the capacity of MSCs to inhibit the proliferation of proinflammatory T lymphocytes, which appear responsible for causing autoimmune disease, have yet to be fully elucidated. One of the underlying mechanisms studied recently is the ability of MSCs to generate T regulatory (Treg) cells in vitro and in vivo from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and also T-CD8(+) cells. In the present work we investigated the capacity of MSCs to generate Treg cells using T-CD4(+) cells induced to differentiate toward the proinflammatory Th1 and Th17 lineages. MSCs were obtained from mouse bone marrow and characterized according to their surface antigen expression and their multilineage differentiation potential. CD4(+) T cells isolated from mouse spleens were induced to differentiate into Th1 or Th17 cells and co-cultured with MSCs added at day 0, 2 or 4 of the differentiation processes. After six days, CD25, Foxp3, IL-17 and IFN-γ expression was assessed by flow cytometry and helios and neuropilin 1 mRNA levels were assessed by RT-qPCR. For the functional assays, the 'conditioned' subpopulation generated in the presence of MSCs was cultured with concanavalin A-activated CD4(+) T cells labeled with carboxyfluorescein succinimidyl ester. Finally, we used the encephalomyelitis autoimmune diseases (EAE) mouse model, in which mice were injected with MSCs at day 18 and 30 after immunization. At day 50, the mice were euthanized and draining lymph nodes were extracted for Th1, Th17 and Treg detection by flow cytometry. MSCs were able to suppress the proliferation, activation and differentiation of CD4(+) T cells induced to differentiate into Th1 and Th17 cells. This substantial suppressive effect was associated with an increase of the percentage of functional induced CD4(+)CD25(+)Foxp3(+) regulatory T cells and IL-10 secretion. However

  7. Report on the 4th International IUPAP Women in Physics Conference

    NASA Astrophysics Data System (ADS)

    Correa, Cynthia

    2011-10-01

    Stellenbosch, South Africa was the site of the 4^th International Union of Pure and Applied Physics (IUPAP) International Conference on Women in Physics, which took place on April 5^th-8^th. This conference brought together the diverse contributions of 250 female physicist attendees from nearly 60 countries worldwide to dissect the challenges faced by female physicists worldwide and to propose strategies to attract and retain more girls and women to the field. Having served as a member of the U.S. Delegation, I will discuss the resolutions reached and highlight the most important results of Global Survey of Physicists, where nearly 15,000 physicists shine light on how gender affects their lives and careers.

  8. 4th integrated transportation management systems (ITMS) conference : conference proceedings

    DOT National Transportation Integrated Search

    2001-08-01

    This report documents the proceedings from the 4th Integrated Transportation Management Systems (ITMS) Conference, ITMS: A Key Strategy to Optimize Surface Transportation System Performance, held in Newark, New Jersey on July 15-18, 2001. The Confere...

  9. 4th International Plant Biomechanics Conference Proceedings (Abstracts)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Frank W. Telewski; Lothar H. Koehler; Frank W. Ewers

    2003-07-20

    The 4th International Plant Biomechanics Conference facilitated an interdisciplinary exchange between scientists, engineers, and educators addressing the major questions encountered in the field of Plant Biomechanics. Subjects covered by the conference include: Evolution; Ecology; Mechanoreception; Cell Walls; Genetic Modification; Applied Biomechanics of Whole Plants, Plant Products, Fibers & Composites; Fluid Dynamics; Wood & Trees; Fracture Mechanics; Xylem Pressure & Water Transport; Modeling; and Introducing Plant Biomechanics in Secondary School Education.

  10. The Effects of Cooperative Learning Strategies on Vocabulary Skills of 4th Grade Students

    ERIC Educational Resources Information Center

    Bilen, Didem; Tavil, Zekiye Müge

    2015-01-01

    This study was carried out to investigate the effects of cooperative learning strategies on the vocabulary skills of 4th grade students. The study was also designed to ascertain the attitudes of the students in the experimental group towards cooperative learning. Out of 96 4th grade students enrolled in the private school where the study took…

  11. 4th integrated transportation management systems (ITMS) conference : white papers

    DOT National Transportation Integrated Search

    2001-07-01

    This report provides the technical papers prepared for the 4th Integrated Transportation Management Systems (ITMS) Conference held in Newark, New Jersey on July 15-18, 2001. The Conference was sponsored by the Transportation Research Board (TRB), the...

  12. 11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry

    PubMed Central

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B.; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho e Melo, Teresa M.V.D.; Freitas, Victor

    2016-01-01

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

  13. Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity.

    PubMed

    Zander, Ryan A; Vijay, Rahul; Pack, Angela D; Guthmiller, Jenna J; Graham, Amy C; Lindner, Scott E; Vaughan, Ashley M; Kappe, Stefan H I; Butler, Noah S

    2017-11-14

    Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. 75 FR 34374 - Safety Zone; Stockton Ports Baseball Club/City of Stockton, 4th of July Fireworks Display...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ...-AA00 Safety Zone; Stockton Ports Baseball Club/City of Stockton, 4th of July Fireworks Display... July 4th fireworks display. This safety zone is established to ensure the safety of participants and... will sponsor the Stockton Ports Baseball Club/City of Stockton 4th of July Fireworks Display on July 4...

  15. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma.

    PubMed

    Shi, Yu-heng; Shi, Guo-chao; Wan, Huan-ying; Jiang, Li-hua; Ai, Xiang-yan; Zhu, Hai-xing; Tang, Wei; Ma, Jia-yun; Jin, Xiao-yan; Zhang, Bo-ying

    2011-07-05

    Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4(+) T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells in patients with allergic asthma. Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4(+)CD25(+) Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.

  16. [Anti-feeding activity of total ginsenoside from Panax ginseng to 4th-instar Mythimna separata larvae].

    PubMed

    Tan, Shi-qiang; Ma, Lin; Xu, Yong-hua; Lei, Feng-jie; Zhang, Ai-hua; Zhang, Lian-xue

    2015-07-01

    This paper is in order to study the anti-feeding and growth inhibition activity of toatal ginsenoside of ginseng stems and leaves against 4th-instar Mythimna separata larvae. Simulating natural growing condition indoors, on the base, To study the anti-feeding and growth inhibition activity of toatal ginsenoside against 4th-instar M. separata larvae by leaf disc test. The toatal ginsenoside appeared to be of significant antifeeding activity against 4th-instar M. separata larvae. The 4th-instar M. separata larvae fed on the leaves of Sorghum bicolor treated with 20, 10, 5 g · L(-1) toatal ginsenoside. At 8 h, non-selective anti-feeding rate were 88.67%, 64.40% and 47.36%, and selective anti-feeding rate were 62.49% , 44.29% and 34.19%; Compared with the photographic, The toatal ginsenoside conld make the development period had prolonged 13h in treated group. The toatal ginsenoside had significant inhibition effect on feeding and growth and development against 4th-instar M. separata larvae, and inhibition effect increases as the increase of concentration ginsenoside.

  17. Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function.

    PubMed

    Karim, Ahmad Faisal; Reba, Scott M; Li, Qing; Boom, W Henry; Rojas, Roxana E

    2017-09-01

    We have recently demonstrated that mycobacterial ligands engage Toll like receptor 2 (TLR2) on CD4 + T cells and up-regulate T-cell receptor (TCR) triggered Th1 responses in vitro and in vivo. To better understand the role of T-cell expressed TLR2 on CD4 + T-cell differentiation and function, we conducted a gene expression analysis of murine naïve CD4 + T-cells stimulated in the presence or absence of TLR2 co-stimulation. Unexpectedly, naïve CD4 + T-cells co-stimulated via TLR2 showed a significant up-regulation of Il9 mRNA compared to cells co-stimulated via CD28. Under TH9 differentiation, we observed up-regulation of TH9 differentiation, evidenced by increases in both percent of IL-9 secreting cells and IL-9 in culture supernatants in the presence of TLR2 agonist both in polyclonal and Ag85B cognate peptide specific stimulations. Under non-polarizing conditions, TLR2 engagement on CD4 + T-cells had minimal effect on IL-9 secretion and TH9 differentiation, likely due to a prominent effect of TLR2 signaling on IFN-γ secretion and TH1 differentiation. We also report that, TLR2 signaling in CD4 + T cells increased expression of transcription factors BATF and PU.1, known to positively regulate TH9 differentiation. These results reveal a novel role of T-cell expressed TLR2 in enhancing the differentiation and function of TH9 T cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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.

  19. THE FIRST LASING OF 193 NM SASE, 4TH HARMONIC HGHG AND ESASE AT THE NSLS SDL.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    WANG, X.J.; SHEN Y.; WATANABE, T.

    2006-08-28

    The first lasing of three types of single-pass high-gain FELs, SASE at 193 nm, 4th harmonic HGHG at 199 nm and ESASE at the Source Development Lab (SDL) of Brookhaven National Laboratory (BNL) is reported. The saturation of 4th harmonic HGHG and ESASE FELs was observed. We also observed the spectral broadening and instability of the 4th harmonic HGHG.

  20. Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.

    PubMed

    Pelly, Victoria S; Coomes, Stephanie M; Kannan, Yashaswini; Gialitakis, Manolis; Entwistle, Lewis J; Perez-Lloret, Jimena; Czieso, Stephanie; Okoye, Isobel S; Rückerl, Dominik; Allen, Judith E; Brombacher, Frank; Wilson, Mark S

    2017-06-05

    Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4 + Foxp3 + regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex-T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3 + cells after Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus Through selective deletion of Il4ra on Foxp3 + cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell-mediated suppression. © 2017 Pelly et al.

  1. Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths

    PubMed Central

    Coomes, Stephanie M.; Kannan, Yashaswini; Entwistle, Lewis J.; Perez-Lloret, Jimena; Czieso, Stephanie

    2017-01-01

    Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+ regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex–T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells after Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell–mediated suppression. PMID:28507062

  2. Normal limits of pediatric Frank lead electrocardiograms. Differences in data obtained in 4th or 5th intercostal spaces.

    PubMed

    Robert, A; Derwael-Barchy, C; Fesler, R; Brasseur, L A; Brohet, C R

    1984-01-01

    Frank lead electrocardiograms (VCGs) were recorded from 970 young subjects in order to establish normal limits for pediatric VCGs. In 245 children and 231 adolescents, the thoracic electrodes were located at the levels of the 4th and of the 5th intercostal space with subjects in supine position. Pairwise comparisons of 211 linear and angular parameters were made, using the 4th interspace as the reference. In children, there were 155 parameters with statistically significant differences and 56 parameters without significant differences between levels 4 and 5. In adolescents, corresponding figures were 158 parameters with significant differences and 53 without. Results for selected measurements showed an increase of the amplitude of Q and R waves in leads X and Y, a decrease of Q and R waves in lead Z and an increase of maximal spatial and planar QRS vectors, with the QRS loop being more anteriorly oriented by shifting the electrodes from level 4 to level 5. The mean differences in amplitude and orientation were generally small and of little practical value. However, the percentile distribution of the differences indicated that substantial changes in either direction can occur in some subjects. Thus, quantitative analysis of the pediatric Frank VCGs can be critically affected by modification of electrode placement. It is suggested that normal limits should be determined for each recording level and that criteria for analysis should be applied only to VCGs recorded at the same specified level.

  3. 77 FR 39422 - Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ...-AA00 Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou... Guard will enforce a Safety Zone for the Niceville July 4th Fireworks Show in Boggy Bayou, Niceville... July 4th Fireworks Show. During the enforcement period, entry into, transiting or anchoring in the...

  4. 29. VIEW OF 4TH FLOOR'S TELEPHONE RACKS WITH CABLE TRAYS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. VIEW OF 4TH FLOOR'S TELEPHONE RACKS WITH CABLE TRAYS ABOVE. THESE ARE NEWER APPARATUS AND NOT ORIGINAL. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  5. 1. WEST AND NORTH (OBLIQUE VIEW) SIDES, FROM ACROSS 4TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. WEST AND NORTH (OBLIQUE VIEW) SIDES, FROM ACROSS 4TH STREET, LOOKING SOUTHEAST. - Oakland Naval Supply Center, Warehouse, North of A Street, between Fourth & Maritime Streets, Oakland, Alameda County, CA

  6. Prevention of autoantibody-mediated Graves'-like hyperthyroidism in mice with IL-4, a Th2 cytokine.

    PubMed

    Nagayama, Yuji; Mizuguchi, Hiroyuki; Hayakawa, Takao; Niwa, Masami; McLachlan, Sandra M; Rapoport, Basil

    2003-04-01

    Graves' hyperthyroidism has long been considered to be a Th2-type autoimmune disease because it is directly mediated by autoantibodies against the thyrotropin receptor (TSHR). However, several lines of evidence have recently challenged this concept. The present study evaluated the Th1/Th2 paradigm in Graves' disease using a recently established murine model involving injection of adenovirus expressing the TSHR (AdCMVTSHR). Coinjection with adenovirus expressing IL-4 (AdRGDCMVIL-4) decreased the ratio of Th1/Th2-type anti-TSHR Ab subclasses (IgG2a/IgG1) and suppressed the production of IFN-gamma by splenocytes in response to TSHR Ag. Importantly, immune deviation toward Th2 was accompanied by significant inhibition of thyroid-stimulating Ab production and reduction in hyperthyroidism. However, in a therapeutic setting, injection of AdRGDCMVIL-4 alone or in combination with AdCMVTSHR into hyperthyroid mice had no beneficial effect. In contrast, coinjection of adenoviruses expressing IL-12 and the TSHR promoted the differentiation of Th1-type anti-TSHR immune responses as demonstrated by augmented Ag-specific IFN-gamma secretion from splenocytes without changing disease incidence. Coinjection of adenoviral vectors expressing IL-4 or IL-12 had no effect on the titers of anti-TSHR Abs determined by ELISA or thyroid-stimulating hormone-binding inhibiting Ig assays, suggesting that Ab quality, not quantity, is responsible for disease induction. Our observations demonstrate the critical role of Th1 immune responses in a murine model of Graves' hyperthyroidism. These data may raise a cautionary note for therapeutic strategies aimed at reversing Th2-mediated autoimmune responses in Graves' disease in humans.

  7. 75 FR 33170 - Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2010-0371] RIN 1625-AA00 Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA AGENCY: Coast Guard, DHS. ACTION... of Martinez 4th of July Fireworks, Martinez, CA. (a) Location. This temporary safety zone is...

  8. Cyanidin-3-glucoside suppresses Th2 cytokines and GATA-3 transcription factor in EL-4 T cells.

    PubMed

    Pyo, Myoung Yun; Yoon, Soo Jeong; Yu, Yeonsil; Park, Sunyoung; Jin, Mirim

    2014-01-01

    Allergic disease is dominated by Th2 immune responses. Interleukin (IL)-4 and IL-13, representative Th2 cytokines, play pivotal roles in the pathogenic activation of the Th2 immune response. In this study, we found that cyanidin-3-glucoside chloride (C3G), an anthocyanin suppressed IL-4 and IL-13 produced in activated EL-4 T cells but not Th1 cytokines including IL-2, interferon-γ, or IL-12. IL-4 and IL-13 mRNA levels and luciferase activation in cells transiently transfected with IL-4 and IL-13 promoter reporter plasmids were significantly inhibited by C3G, suggesting that suppression might be, at least in part, regulated at the transcriptional level. Data from western blot and reverse transcription-polymerase chain reaction analyses of transcription factors involved in cytokine expression suggested that expression of GATA-3, but not T-bet, was downregulated in the nucleus by C3G. Taken together, our data indicate that C3G may has potential as an anti-allergic agent suppressing Th2 activation by downregulating Th2 cytokines and the GATA3 transcription factor in allergies.

  9. Rapid stimulation of sodium intake combining aldosterone into the 4th ventricle and the blockade of the lateral parabrachial nucleus.

    PubMed

    Gasparini, S; Melo, M R; Leite, G F; Nascimento, P A; Andrade-Franzé, G M F; Menani, J V; Colombari, E

    2017-03-27

    Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α 2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted in the 4th V and bilaterally in the LPBN were used. Aldosterone (250 or 500ng) into the 4th V combined with vehicle into the LPBN induced no 1.8% NaClintake compared to control (1.5±1.1 and 1.1±0.4, respectively, vs. vehicle into 4th V: 1.0±0.5ml/2h). However, aldosterone (250 or 500ng) into the 4th V combined with moxonidine (0.5nmol) into the LPBN induced strong ingestion of 1.8% NaCl (12.7±4.6 and 17.6±3.7ml/2h, respectively). Aldosterone (250ng) into the 4th V combined with methysergide (4μg) into the LPBN also induced 1.8% NaCl intake (17.6±5.4ml/2h). These data suggest that the inhibitory mechanisms of the LPBN counteract the facilitation of sodium intake produced by aldosterone injected into the 4th, restraining sodium intake in this condition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. 18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING TRANSITION FROM WOOD BENTS TO CONCRETE BENTS - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  11. Th1, Th2, and Th17 Cytokine Involvement in Thyroid Associated Ophthalmopathy

    PubMed Central

    Shen, Jie; Li, Zhangfang; Li, Wenting; Ge, Ying; Xie, Min; Lv, Meng; Fan, Yanfei; Chen, Zhi; Zhao, Defu; Han, Yajuan

    2015-01-01

    To determine serum cytokine profiles in Graves' disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ (interferon-gamma), TNF-α (tumor necrosis factor-alpha), IL-1α (interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γ and TNF-α were elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis. PMID:26089587

  12. 97. VIEW NORTHWEST OF 4TH FLOOR OF BUILDING 112; NOTE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    97. VIEW NORTHWEST OF 4TH FLOOR OF BUILDING 112; NOTE REMNANTS OF BEARING SUPPORTS FOR OVERHEAD BELT AND PULLEY POWER TRANSMISSION SYSTEM - Scovill Brass Works, 59 Mill Street, Waterbury, New Haven County, CT

  13. 4th floor sacking deck looking east from 1945 elevator to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th floor sacking deck looking east from 1945 elevator to 1913 elevator indicating spout used to load bulk grain into rail cars - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  14. Report of the 4th European Zebrafish Principal Investigator Meeting.

    PubMed

    Lopes, Susana S; Distel, Martin; Linker, Claudia; Fior, Rita; Monteiro, Rui; Bianco, Isaac H; Portugues, Ruben; Strähle, Uwe; Saúde, Leonor

    2016-12-01

    The European Zebrafish Principal Investigator Meeting (EZPM) is an ideal forum for group leaders using this fantastic animal model not only to discuss science but also to strengthen their interactions, to push forward technological advances, and to define guidelines for the use of this fish in research. The city of Lisbon (Portugal) was voted by the European group leaders to be the setting for the 4th EZPM, and the organizing committee, composed by Leonor Saúde (iMM Lisboa, PT), Susana Lopes (CEDOC, PT), Michael Orger (Champalimaud Foundation, PT), Rui Oliveira (ISPA, PT), and António Jacinto (CEDOC, PT), was very enthusiastic to organize a productive event. The 4th EZPM took place from March 15 to 19 at Pavilhão do Conhecimento, a Science Museum and Educational Center winner of The Great Prize FAD of Arquitecture 1999 and The Society for Environmental Graphic Design Award 2011. Over 5 days, 135 group leaders (89 men and 46 women) coming from 19 different European countries and also from the United States, Turkey, Israel, Chile, and Singapore presented and discussed their recent research achievements. In addition to the scientific oral and poster presentations, the group leaders gathered in very lively community sessions on morphants versus mutants (chaired by Didier Stainier, Max Planck Institute for Heart and Lung Research, DE), funding issues (chaired by Uwe Strahle, KIT-ITG, DE), and gender equality (chaired by Corinne Houart, KCL, United Kingdom). One of the highlights of the 4th EZPM was the guided visit to Oceanário de Lisboa, an international award-winning place that celebrates life with a stunning display of living aquatic creatures.

  15. 5. Double crib barn, main floor, 4th room from northeast, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Double crib barn, main floor, 4th room from northeast, southeast and southwest walls - Wilkins Farm, Barn, South side of Dove Hollow Road, 6000 feet east of State Route 259, Lost City, Hardy County, WV

  16. Charactering baseline shift with 4th polynomial function for portable biomedical near-infrared spectroscopy device

    NASA Astrophysics Data System (ADS)

    Zhao, Ke; Ji, Yaoyao; Pan, Boan; Li, Ting

    2018-02-01

    The continuous-wave Near-infrared spectroscopy (NIRS) devices have been highlighted for its clinical and health care applications in noninvasive hemodynamic measurements. The baseline shift of the deviation measurement attracts lots of attentions for its clinical importance. Nonetheless current published methods have low reliability or high variability. In this study, we found a perfect polynomial fitting function for baseline removal, using NIRS. Unlike previous studies on baseline correction for near-infrared spectroscopy evaluation of non-hemodynamic particles, we focused on baseline fitting and corresponding correction method for NIRS and found that the polynomial fitting function at 4th order is greater than the function at 2nd order reported in previous research. Through experimental tests of hemodynamic parameters of the solid phantom, we compared the fitting effect between the 4th order polynomial and the 2nd order polynomial, by recording and analyzing the R values and the SSE (the sum of squares due to error) values. The R values of the 4th order polynomial function fitting are all higher than 0.99, which are significantly higher than the corresponding ones of 2nd order, while the SSE values of the 4th order are significantly smaller than the corresponding ones of the 2nd order. By using the high-reliable and low-variable 4th order polynomial fitting function, we are able to remove the baseline online to obtain more accurate NIRS measurements.

  17. A thermodynamic study of the gaseous thorium carbides, ThC, ThC2, ThC3, ThC4, ThC5, and ThC6

    NASA Astrophysics Data System (ADS)

    Gupta, Satish K.; Gingerich, Karl A.

    1980-02-01

    Six gaseous carbides of thorium, ThCn(n=1-6), have been identified in a Knudsen effusion mass spectrometric investigation of the vapor phase above a thorium-uranium-rhodium-graphite system at high temperatures. The partial pressures of the thorium containing species were measured as a function of temperature in the 2300-2700 °K range. Third law enthalpies for the reactions Th(g)+nC(graphite) =ThCn, n=1 to 6, and of various other homogeneous and heterogeneous reactions were evaluated. By combining the experimental enthalpies with appropriate thermodynamic data taken from literature, the following values for the atomization energies ΔH °at,298, and standard heats of formation ΔH °f,298 of thorium carbides have been derived:

  18. Fine PM2.5 around July 4th

    EPA Pesticide Factsheets

    Data used in these analyses was obtained from publically-available sources, specifically the EPA's AirNow website (https://www.epa.gov/outdoor-air-quality-data). The dataset provided includes the subset of data from AirNow that was used in our analyses.This dataset is associated with the following publication:Dickerson, A., A. Benson, B. Buckley, and E. Chan. Concentrations of individual fine particulate matter components in the United States around July 4th. Air Quality, Atmosphere & Health. Springer Netherlands, NETHERLANDS, 1-10, (2016).

  19. TID Test Results for 4th Generation iPad(TradeMark)

    NASA Technical Reports Server (NTRS)

    Guertin, S. M.; Allen, G. R.; McClure, S. S.; LaBel, K. A.

    2013-01-01

    TID testing of 4th generation iPads is reported. Of iPad subsystems, results indicate that the charging circuitry and display drivers fail at lowest TID levels. Details of construction are investigated for additional testing of components.

  20. 29. 4TH STREET FROM NEAR ITS INTERSECTION WITH J STREET, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. 4TH STREET FROM NEAR ITS INTERSECTION WITH J STREET, LOOKING NORTH, WITH WAREHOUSE 333 AT LEFT AND WAREHOUSES 433, 432 & 431 AT RIGHT. - Oakland Naval Supply Center, Maritime Street at Seventh Street, Oakland, Alameda County, CA

  1. Magendie and Luschka: Holes in the 4th ventricle.

    PubMed

    Engelhardt, Eliasz

    2016-01-01

    Cerebrospinal fluid (CSF) is a complex liquid formed mainly by the choroid plexuses. After filling the ventricular system where it circulates, CSF flows out to the subarachnoid spaces through openings in the 4 th ventricle. Following numerous studies on CSF pathways, these openings were first discovered in the 19 th century by two notable researchers, François Magendie and Hubert von Luschka, who described the median and lateral openings subsequently named after them. Even after the studies of Axel Key and Gustav Magnus Retzius confirming these openings, their existence was questioned by many anatomists, yet acknowledged by others. Finally gaining the acceptance of all, recognition of the holes endures to the present day. Interest in these openings may be attributed to the several congenital or acquired pathological conditions that may affect them, usually associated with hydrocephalus. We report some historical aspects of these apertures and their discoverers.

  2. 4th level of 1913 elevator indicating sacking scale, part of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  3. Immobilization of Alkali Metal Fluorides via Recrystallization in a Cationic Lamellar Material, [Th(MoO4)(H2O)4Cl]Cl·H2O.

    PubMed

    Lin, Jian; Bao, Hongliang; Qie, Meiying; Silver, Mark A; Yue, Zenghui; Li, Xiaoyun; Zhu, Lin; Wang, Xiaomei; Zhang, Linjuan; Wang, Jian-Qiang

    2018-06-05

    Searching for cationic extended materials with a capacity for anion exchange resulted in a unique thorium molybdate chloride (TMC) with the formula of [Th(MoO 4 )(H 2 O) 4 Cl]Cl·H 2 O. The structure of TMC is composed of zigzagging cationic layers [Th(MoO 4 )(H 2 O) 4 Cl] + with Cl - as interlamellar charge-balancing anions. Instead of performing ion exchange, alkali thorium fluorides were formed after soaking TMC in AF (A = Na, K, and Cs) solutions. The mechanism of AF immobilization is elucidated by the combination of SEM-EDS, PXRD, FTIR, and EXAFS spectroscopy. It was observed that four water molecules coordinating with the Th 4+ center in TMC are vulnerable to competition with F - , due to the formation of more favorable Th-F bonds compared to Th-OH 2 . This leads to a single crystal-to-polycrystalline transformation via a pathway of recrystallization to form alkali thorium fluorides.

  4. Reading Development and Achievement of 4th-Grade Hmong Students

    ERIC Educational Resources Information Center

    Mahowald, Megan; Loughnane, Megan

    2016-01-01

    Researchers and practitioners alike have noted that Hmong students in the United States do not achieve as well as their monolingual peers and other bilingual students. The current mixed-methods study is designed to describe reading development and achievement of 4th-grade Hmong students in one large, urban school district. This study explores the…

  5. Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells.

    PubMed

    Duechting, Andrea; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

    2017-09-12

    During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.

  6. 77 FR 38486 - Safety Zone; City of Tonawanda July 4th Celebration, Niagara River, Tonawanda, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-28

    ... 1625-AA00 Safety Zone; City of Tonawanda July 4th Celebration, Niagara River, Tonawanda, NY AGENCY... safety zone on the Niagara River, Tonawanda, New York. This safety zone is intended to restrict vessels from a portion of the Niagara River during the City of Tonawanda July 4th Celebration fireworks on July...

  7. 4. Photocopy of old 19th century photo showing a steam ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of old 19th century photo showing a steam engine in active use. Original photo in files of Insurance Company of North America, Philadelphia, Pa. Exact date not known. - Philadelphia Hose Company No. 1, Seventh & Filbert Streets, Philadelphia, Philadelphia County, PA

  8. 55. TOP (4TH) FLOOR OF 187380 WING LOOKING NORTH, WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    55. TOP (4TH) FLOOR OF 1873-80 WING LOOKING NORTH, WEST SIDE. NOTE SECTION, LEFT SIDE, MIDDLEGROUND, WHERE SMALL HIGH WINDOWS INDICATE POINT AT WHICH 1852 WING JOINS THIS WING. - Boston Manufacturing Company, 144-190 Moody Street, Waltham, Middlesex County, MA

  9. 45. Master plan of 4th floor, building 1, U.S. Naval ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. Master plan of 4th floor, building 1, U.S. Naval supply activities, New York, Brooklyn, New York, public works department, March 2, 1953. Drawing #BK-S1-4. Scale 1/16=1. - U.S. Navy Fleet Supply Base, Storehouse No. 1, 830 Third Avenue, Brooklyn, Kings County, NY

  10. P(4-vinyl pyridine) hydrogel use for the removal of UO(2)(2+) and Th(4+) from aqueous environments.

    PubMed

    Ozay, Ozgur; Ekici, Sema; Aktas, Nahit; Sahiner, Nurettin

    2011-12-01

    4-vinyl pyridine (4-VP) based hydrogels with 2-hydroxyethylmetacrylate (HEMA) and magnetic composites were prepared and tested for use in the removal of UO(2)(2+) and Th(4+) ions from aqueous environments. It was found that the absorption of these metal ions from aqueous environments decreased with an increase in the amount of HEMA contained within p(4-VP-co-HEMA) hydrogels between 0.498 mmol for pure p(4-VP) and 0.027 mmol for pure p(HEMA). The characterization of the hydrogels was determined by swelling experiments, FT-IR and thermal analysis. The effects of initial metal ion concentration, hydrogel amount and the temperature of the medium on absorption of the ions were investigated. Langmuir and Freundlich isotherms were constructed for the absorption of UO(2)(2+) and Th(4+). Both isotherms demonstrated that these metal ions complied with monolayer absorption kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Teaching systems thinking to 4th and 5th graders using Environmental Dashboard display technology.

    PubMed

    Clark, Shane; Petersen, John E; Frantz, Cindy M; Roose, Deborah; Ginn, Joel; Rosenberg Daneri, Daniel

    2017-01-01

    Tackling complex environmental challenges requires the capacity to understand how relationships and interactions between parts result in dynamic behavior of whole systems. There has been convincing research that these "systems thinking" skills can be learned. However, there is little research on methods for teaching these skills to children or assessing their impact. The Environmental Dashboard is a technology that uses "sociotechnical" feedback-information feedback designed to affect thought and behavior. Environmental Dashboard (ED) combines real-time information on community resource use with images and words that reflect pro-environmental actions of community members. Prior research indicates that ED supports the development of systems thinking in adults. To assess its impact on children, the technology was installed in a primary school and children were passively exposed to ED displays. This resulted in no measurable impact on systems thinking skills. The next stage of this research examined the impact of actively integrating ED into lessons on electricity in 4th and 5th grade. This active integration enhanced both content-related systems thinking skills and content retention.

  12. Teaching systems thinking to 4th and 5th graders using Environmental Dashboard display technology

    PubMed Central

    Clark, Shane; Frantz, Cindy M.; Roose, Deborah; Ginn, Joel; Rosenberg Daneri, Daniel

    2017-01-01

    Tackling complex environmental challenges requires the capacity to understand how relationships and interactions between parts result in dynamic behavior of whole systems. There has been convincing research that these “systems thinking” skills can be learned. However, there is little research on methods for teaching these skills to children or assessing their impact. The Environmental Dashboard is a technology that uses “sociotechnical” feedback–information feedback designed to affect thought and behavior. Environmental Dashboard (ED) combines real-time information on community resource use with images and words that reflect pro-environmental actions of community members. Prior research indicates that ED supports the development of systems thinking in adults. To assess its impact on children, the technology was installed in a primary school and children were passively exposed to ED displays. This resulted in no measurable impact on systems thinking skills. The next stage of this research examined the impact of actively integrating ED into lessons on electricity in 4th and 5th grade. This active integration enhanced both content-related systems thinking skills and content retention. PMID:28448586

  13. Registration of High Angular Resolution Diffusion MRI Images Using 4th Order Tensors⋆

    PubMed Central

    Barmpoutis, Angelos; Vemuri, Baba C.; Forder, John R.

    2009-01-01

    Registration of Diffusion Weighted (DW)-MRI datasets has been commonly achieved to date in literature by using either scalar or 2nd-order tensorial information. However, scalar or 2nd-order tensors fail to capture complex local tissue structures, such as fiber crossings, and therefore, datasets containing fiber-crossings cannot be registered accurately by using these techniques. In this paper we present a novel method for non-rigidly registering DW-MRI datasets that are represented by a field of 4th-order tensors. We use the Hellinger distance between the normalized 4th-order tensors represented as distributions, in order to achieve this registration. Hellinger distance is easy to compute, is scale and rotation invariant and hence allows for comparison of the true shape of distributions. Furthermore, we propose a novel 4th-order tensor re-transformation operator, which plays an essential role in the registration procedure and shows significantly better performance compared to the re-orientation operator used in literature for DTI registration. We validate and compare our technique with other existing scalar image and DTI registration methods using simulated diffusion MR data and real HARDI datasets. PMID:18051145

  14. Identification of 4th intercostal space using sternal notch to xiphoid length for accurate electrocardiogram lead placement.

    PubMed

    Day, Kevin; Oliva, Isabel; Krupinski, Elizabeth; Marcus, Frank

    2015-01-01

    Precordial ECG lead placement is difficult in obese patients with increased chest wall soft tissues due to inaccurate palpation of the intercostal spaces. We investigated whether the length of the sternum (distance between the sternal notch and xiphoid process) can accurately predict the location of the 4th intercostal space, which is the traditional location for V1 lead position. Fifty-five consecutive adult chest computed tomography examinations were reviewed for measurements. The sternal notch to right 4th intercostal space distance was 67% of the sternal notch to xiphoid process length with an overall correlation of r=0.600 (p<0.001). The above measurement may be utilized to locate the 4th intercostal space for accurate placement of the precordial electrodes in adults in whom the 4th intercostal space cannot be found by physical exam. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 4. Photocopy of early 20th century photo of the bridge. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of early 20th century photo of the bridge. Donated to HAER for its collection at the Library of Congress; donation courtesy of the Erie Railroad Company. - Erie Railway, Moodna Creek Viaduct, Moodna Creek, Orrs Mill Road, Salisbury Mills, Orange County, NY

  16. Th40 cells (CD4+CD40+ Tcells) drive a more severe form of Experimental Autoimmune Encephalomyelitis than conventional CD4 T cells

    PubMed Central

    Vaitaitis, Gisela M.; Yussman, Martin G.; Waid, Dan M.; Wagner, David H.

    2017-01-01

    CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination. Primary Th40 cells from EAE-induced donors adoptively transfer EAE without further in-vitro expansion and without requiring the administration of the EAE induction regimen to the recipient animals. This has not been accomplished with primary, non-TCR-transgenic donor cells previously. If co-injection of Th40 donor cells with Freund’s adjuvant (CFA) in the recipient animals is done, the disease course is more severe. The CFA component of the EAE induction regimen causes generalized inflammation, promoting expansion of Th40 cells and infiltration of the CNS, while MOG-antigen shapes the antigen-specific TCR repertoire. Those events are both necessary to precipitate disease. In MS, viral infections or trauma may induce generalized inflammation in susceptible individuals with subsequent disease onset. It will be important to further understand the events leading up to disease onset and to elucidate the contributions of the Th40 T cell subset. Also, evaluating Th40 levels as predictors of disease onset would be highly useful because if either the generalized inflammation event or the TCR-honing can be interrupted, disease onset may be prevented. PMID:28192476

  17. U.S. Dietary and Physical Activity Guideline Knowledge and Corresponding Behaviors among 4th and 5th Grade Students: A Multi-Site Pilot Study

    ERIC Educational Resources Information Center

    Bea, Jennifer W.; Martinez, Stephanie; Armstrong-Florian, Traci; Farrell, Vanessa; Martinez, Cathy; Whitmer, Evelyn; Hartz, Vern; Blake, Samuel; Nicolini, Ariana; Misner, Scottie

    2014-01-01

    Knowledge of U.S. dietary and physical activity recommendations and corresponding behaviors were surveyed among 4th and 5th graders in five Arizona counties to determine the need for related education in SNAP-Ed eligible schools. A <70% target response rate was the criterion. Participants correctly identified recommendations for: fruit, 20%;…

  18. STAT4 Deficiency Fails To Induce Lung Th2 or Th17 Immunity following Primary or Secondary Respiratory Syncytial Virus (RSV) Challenge but Enhances the Lung RSV-Specific CD8+ T Cell Immune Response to Secondary Challenge

    PubMed Central

    Dulek, Daniel E.; Newcomb, Dawn C.; Toki, Shinji; Goliniewska, Kasia; Cephus, Jacqueline; Reiss, Sara; Bates, John T.; Crowe, James E.; Boyd, Kelli L.; Moore, Martin L.; Zhou, Weisong

    2014-01-01

    ABSTRACT Immune-mediated lung injury is a hallmark of lower respiratory tract illness caused by respiratory syncytial virus (RSV). STAT4 plays a critical role in CD4+ Th1 lineage differentiation and gamma interferon (IFN-γ) protein expression by CD4+ T cells. As CD4+ Th1 differentiation is associated with negative regulation of CD4+ Th2 and Th17 differentiation, we hypothesized that RSV infection of STAT4−/− mice would result in enhanced lung Th2 and Th17 inflammation and impaired lung Th1 inflammation compared to wild-type (WT) mice. We performed primary and secondary RSV challenges in WT and STAT4−/− mice and used STAT1−/− mice as a positive control for the development of RSV-specific lung Th2 and Th17 inflammation during primary challenge. Primary RSV challenge of STAT4−/− mice resulted in decreased T-bet and IFN-γ expression levels in CD4+ T cells compared to those of WT mice. Lung Th2 and Th17 inflammation did not develop in primary RSV-challenged STAT4−/− mice. Decreased IFN-γ expression by NK cells, CD4+ T cells, and CD8+ T cells was associated with attenuated weight loss and enhanced viral clearance with primary challenge in STAT4−/− mice compared to WT mice. Following secondary challenge, WT and STAT4−/− mice also did not develop lung Th2 or Th17 inflammation. In contrast to primary challenge, secondary RSV challenge of STAT4−/− mice resulted in enhanced weight loss, an increased lung IFN-γ expression level, and an increased lung RSV-specific CD8+ T cell response compared to those of WT mice. These data demonstrate that STAT4 regulates the RSV-specific CD8+ T cell response to secondary infection but does not independently regulate lung Th2 or Th17 immune responses to RSV challenge. IMPORTANCE STAT4 is a protein critical for both innate and adaptive immune responses to viral infection. Our results show that STAT4 regulates the immune response to primary and secondary challenge with RSV but does not restrain RSV

  19. Myosin MyTH4-FERM structures highlight important principles of convergent evolution.

    PubMed

    Planelles-Herrero, Vicente José; Blanc, Florian; Sirigu, Serena; Sirkia, Helena; Clause, Jeffrey; Sourigues, Yannick; Johnsrud, Daniel O; Amigues, Beatrice; Cecchini, Marco; Gilbert, Susan P; Houdusse, Anne; Titus, Margaret A

    2016-05-24

    Myosins containing MyTH4-FERM (myosin tail homology 4-band 4.1, ezrin, radixin, moesin, or MF) domains in their tails are found in a wide range of phylogenetically divergent organisms, such as humans and the social amoeba Dictyostelium (Dd). Interestingly, evolutionarily distant MF myosins have similar roles in the extension of actin-filled membrane protrusions such as filopodia and bind to microtubules (MT), suggesting that the core functions of these MF myosins have been highly conserved over evolution. The structures of two DdMyo7 signature MF domains have been determined and comparison with mammalian MF structures reveals that characteristic features of MF domains are conserved. However, across millions of years of evolution conserved class-specific insertions are seen to alter the surfaces and the orientation of subdomains with respect to each other, likely resulting in new sites for binding partners. The MyTH4 domains of Myo10 and DdMyo7 bind to MT with micromolar affinity but, surprisingly, their MT binding sites are on opposite surfaces of the MyTH4 domain. The structural analysis in combination with comparison of diverse MF myosin sequences provides evidence that myosin tail domain features can be maintained without strict conservation of motifs. The results illustrate how tuning of existing features can give rise to new structures while preserving the general properties necessary for myosin tails. Thus, tinkering with the MF domain enables it to serve as a multifunctional platform for cooperative recruitment of various partners, allowing common properties such as autoinhibition of the motor and microtubule binding to arise through convergent evolution.

  20. 4th level of 1945 warehouse indicating drag conveyor. From here ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th level of 1945 warehouse indicating drag conveyor. From here screenings were pumped from the elevator leg to this conveyor. The grains were ground, then conveyed back down to the first floor for bagging. - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  1. 94. VIEW OF PILINGS ON SOUTHEAST SIDE, WITH 4TH TEE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    94. VIEW OF PILINGS ON SOUTHEAST SIDE, WITH 4TH TEE IN THE BACKGROUND, FACING WEST-SOUTHWEST FROM SOUTHEAST CORNER OF THE TACKLE BOX. RAMP OF PIER EXTENSION IS VISIBLE ON RIGHT - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  2. Improving 4th Grade Primary School Students' Reading Comprehension Skills

    ERIC Educational Resources Information Center

    Bulut, Aydin

    2017-01-01

    The aim of this study was to carry out action research to investigate reading comprehension skills when using the SQ3R reading comprehension strategy. To that end, this strategy was used for improving the reading comprehension skills of 7 primary school 4th grade students who had problems with these skills. An action plan was prepared for 3hours a…

  3. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production

    PubMed Central

    Zhu, Jinfang

    2015-01-01

    Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. PMID:26044597

  4. Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

    PubMed

    Renand, Amedee; Archila, Luis D; McGinty, John; Wambre, Erik; Robinson, David; Hales, Belinda J; Thomas, Wayne R; Kwok, William W

    2015-12-01

    In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  5. Structural study of dehydration mechanisms of NH4Th(NO3)5·9H2O

    NASA Astrophysics Data System (ADS)

    Knyazev, A. V.; Komshina, M. E.; Baranov, E. V.; Savushkin, I. A.; Nipruk, O. V.; Lukoyanov, A. Yu.

    2017-12-01

    The new pentanitrate thorium compounds NH4Th(NO3)5·nH2O were synthesized and their crystal structures were determined by X-ray diffraction analysis: space group P21/n, a = 10.5476(5), b = 14.0444(7), c = 15.5287(8) Å, β = 109.4999(7)°, Z = 4; R = 0.0246 (NH4Th(NO3)5·9H2O); space group P212121, a = 8.7039(4), b = 11.9985(6), c = 16.3531(8) Å, Z = 4; R = 0.0259 (NH4Th(NO3)5·5H2O). Features of structural changes in the dehydration were revealed. Conditions of thermal decomposition of the thorium compound were established using differential scanning calorimetry. The compound was investigated by IR spectroscopy and its bands are assigned.

  6. Galectin-7 promotes proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting The TGFβ/Smad3 pathway.

    PubMed

    Luo, Zhenlong; Ji, Yudong; Tian, Dean; Zhang, Yong; Chang, Sheng; Yang, Chao; Zhou, Hongmin; Chen, Zhonghua Klaus

    2018-06-08

    Galectin-7 (Gal-7) has been associated with cell proliferation and apoptosis. It is known that Gal-7 antagonises TGFβ-mediated effects in hepatocytes by interacting with Smad3. Previously, we have demonstrated that Gal-7 is related to CD4+ T cells responses; nevertheless, its effect and functional mechanism on CD4+ T cells responses remain unclear. The murine CD4+ T cells were respectively cultured with Gal-7, anti-CD3/CD28 mAbs, or with anti-CD3/CD28 mAbs & Gal-7. The effects of Gal-7 on proliferation and the phenotypic changes in CD4+ T cells were assessed by flow cytometry. The cytokines from CD4+ T cells were analysed by quantitative real-time PCR. Subcellular localisation and expression of Smad3 were determined by immunofluorescence staining and Western blot, respectively. Gal-7 enhanced the proliferation of activated CD4+ T cells in a dose- and β-galactoside-dependent manner. Additionally, Gal-7 treatment did not change the ratio of Th2 cells in activated CD4+ T cells, while it increased the ratio of Th1 cells. Gal-7 also induced activated CD4+ T cells to produce a higher level of IFN-γ and TNF-α and a lower level of IL-10. Moreover, Gal-7 treatment significantly accelerated nuclear export of Smad3 in activated CD4+ T cells. These results revealed a novel role of Gal-7 in promoting proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting the TGFβ/Smad3 pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. 75 FR 38718 - Safety Zone; Sault Sainte Marie 4th of July Fireworks, St. Mary's River, Sault Sainte Marie, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ...-AA00 Safety Zone; Sault Sainte Marie 4th of July Fireworks, St. Mary's River, Sault Sainte Marie, MI... restrict vessels from a portion of the St. Mary's River during the Sault Sainte Marie 4th of July Fireworks... the setup and launching of fireworks in conjunction with the Sault Sainte Marie 4th of July Fireworks...

  8. Primary Murine CD4+ T Cells Fail to Acquire the Ability to Produce Effector Cytokines When Active Ras Is Present during Th1/Th2 Differentiation

    PubMed Central

    Janardhan, Sujit V.; Marks, Reinhard; Gajewski, Thomas F.

    2014-01-01

    Constitutive Ras signaling has been shown to augment IL-2 production, reverse anergy, and functionally replace many aspects of CD28 co-stimulation in CD4+ T cells. These data raise the possibility that introduction of active Ras into primary T cells might result in improved functionality in pathologic situations of T cell dysfunction, such as cancer or chronic viral infection. To test the biologic effects of active Ras in primary T cells, CD4+ T cells from Coxsackie-Adenovirus Receptor Transgenic mice were transduced with an adenovirus encoding active Ras. As expected, active Ras augmented IL-2 production in naive CD4+ T cells. However, when cells were cultured for 4 days under conditions to promote effector cell differentiation, active Ras inhibited the ability of CD4+ T cells to acquire a Th1 or Th2 effector cytokine profile. This differentiation defect was not due to deficient STAT4 or STAT6 activation by IL-12 or IL-4, respectively, nor was it associated with deficient induction of T-bet and GATA-3 expression. Impaired effector cytokine production in active Ras-transduced cells was associated with deficient demethylation of the IL-4 gene locus. Our results indicate that, despite augmenting acute activation of naïve T cells, constitutive Ras signaling inhibits the ability of CD4+ T cells to properly differentiate into Th1/Th2 effector cytokine-producing cells, in part by interfering with epigenetic modification of effector gene loci. Alternative strategies to potentiate Ras pathway signaling in T cells in a more regulated fashion should be considered as a therapeutic approach to improve immune responses in vivo. PMID:25397617

  9. Proceedings of the 4th fire in eastern oak forests conference

    Treesearch

    Daniel C. Dey; Michael C. Stambaugh; Stacy L. Clark; Callie J., eds. Schweitzer

    2012-01-01

    Contains 14 full-length papers and 40 abstracts of posters that were presented at the 4th Fire in Eastern Oak Forests conference, held in Springfield, MO, May 17-19, 2011. The conference was attended by over 250 people from 65 different organizations and entities, representing 22 states and 1 Canadian province.

  10. 78 FR 23866 - Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ...-AA00 Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA AGENCY... a temporary safety zone in the navigable waters near Crescent City, CA in support of the Crescent City 4th of July Fireworks on July 4, 2013. This safety zone is necessary to ensure the safety of...

  11. Crime rates and sedentary behavior among 4th grade Texas school children.

    PubMed

    Brown, H Shelton; Pérez, Adriana; Mirchandani, Gita G; Hoelscher, Deanna M; Kelder, Steven H

    2008-05-14

    Although per capita crime has generally fallen over the period which coincides with the obesity epidemic, it has not fallen uniformly across communities. It also has not fallen enough to allay fears on the part of parents. Over the past 30 years, technological changes have made the indoor alternatives to playing outside, where children are more vulnerable to criminal activity, more enjoyable (cable TV, video games, and the internet) and comfortable (the spread of air conditioning to low income neighborhoods). We determined whether indoor sedentary behavior patterns are associated with community crime statistics. 4th graders in the U.S. are typically 9 or 10 years old. We used data from the 2004-2005 Texas School Physical Activity and Nutrition (SPAN) survey linked with U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics data for the years 2000 through 2005 and Texas State data on sexual offenders. The probability-based sample included a total of 7,907 children in grade four. Multistage probability sampling weights were used. The dependent variables included were hours of TV watching, video game playing, computer use and total indoor sedentary behavior after school. Incremental Relative Rates were computed for community crime rates including robberies, all violent crimes, murders, assaults, property crimes, rapes, burglaries, larcenies and motor vehicle thefts as well as for sexual offenders living in the neighborhood. The neighborhood refers to the areas where the students at each school live. In the case of sexual offenders, sexual offenders per capita are estimated using the per capita rate in the zip code of the school attended; all other crime statistics are estimated by the crimes per capita in the police department jurisdiction covering the school attended. After controlling for sex, age, and African-American and Hispanic, cross-sectional associations were determined using multivariate Poisson regression. 4th grade boys were

  12. Crime rates and sedentary behavior among 4th grade Texas school children

    PubMed Central

    Brown, H Shelton; Pérez, Adriana; Mirchandani, Gita G; Hoelscher, Deanna M; Kelder, Steven H

    2008-01-01

    Introduction Although per capita crime has generally fallen over the period which coincides with the obesity epidemic, it has not fallen uniformly across communities. It also has not fallen enough to allay fears on the part of parents. Over the past 30 years, technological changes have made the indoor alternatives to playing outside, where children are more vulnerable to criminal activity, more enjoyable (cable TV, video games, and the internet) and comfortable (the spread of air conditioning to low income neighborhoods). We determined whether indoor sedentary behavior patterns are associated with community crime statistics. 4th graders in the U.S. are typically 9 or 10 years old. Methods We used data from the 2004–2005 Texas School Physical Activity and Nutrition (SPAN) survey linked with U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics data for the years 2000 through 2005 and Texas State data on sexual offenders. The probability-based sample included a total of 7,907 children in grade four. Multistage probability sampling weights were used. The dependent variables included were hours of TV watching, video game playing, computer use and total indoor sedentary behavior after school. Incremental Relative Rates were computed for community crime rates including robberies, all violent crimes, murders, assaults, property crimes, rapes, burglaries, larcenies and motor vehicle thefts as well as for sexual offenders living in the neighborhood. The neighborhood refers to the areas where the students at each school live. In the case of sexual offenders, sexual offenders per capita are estimated using the per capita rate in the zip code of the school attended; all other crime statistics are estimated by the crimes per capita in the police department jurisdiction covering the school attended. After controlling for sex, age, and African-American and Hispanic, cross-sectional associations were determined using multivariate Poisson regression

  13. Th1 differentiation drives the accumulation of intravascular, non-protective CD4 T cells during tuberculosis

    PubMed Central

    Sallin, Michelle A.; Sakai, Shunsuke; Kauffman, Keith D.; Young, Howard A.; Zhu, Jinfang; Barber, Daniel L.

    2017-01-01

    SUMMARY Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1 polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73+CXCR3+T-betdim stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL-12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1+KLRG1+ Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69+CD103+ tissue resident phenotype effectors in lung. In contrast, Th1 cell-derived IFNγ inhibits the accumulation of intravascular CX3CR1+KLRG1+ Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis. PMID:28355562

  14. Can astronomy enhance UNESCO World Heritage recognition? The paradigm of 4th Dynasty Egyptian pyramids

    NASA Astrophysics Data System (ADS)

    Belmonte, Juan Antonio

    2015-08-01

    The pyramids of Egypt, notably those of the 4th Dinasty as Giza, have always be considered an unmistikable part of human world heritage as the only surviving wonders of the Ancient World. Their majesty, technical hability and innovative character have always beeen considered as representative of ancient Egyptian ingenuity. However, past and present fringe theories about the pyramids and astronomy have always polluted the role of our discipline in the design, construction and symbolism of these impressive monuments. This is indeed unfear. Fortunately, things have started to change in the last couple of decades and now astronomy is interpreted as a neccessary tool for the correct interpretation of the astral eschatology present in the 5th and 6th Dynasty Texts of the Pyramids. Although the pyramid complexes of the 4th Dynasty are mute, there is however recent research showing that a strong astral symbolism could be hidden in many aspects of the complex architecture and in the design of these exceptional monuments. This idea comes from several hints obtained not only from planning and construction, but also from epigraphy and the analysis of celestial and local landscapes. Chronology also plays a most relevant role on this. The pyramid complexes of the 4th Dynasty at Meidum, Dahshur, Giza and Abu Rowash -- all of which enjoy UNESCO World Heritage recognition -- willl be scrutinized. As a consequence, we will show how astronomy can certainly enhance the face value of these extraordinary monuments as a definitive proof of the ancient Egyptian quest for Ma'at, i.e. their perennial obsesion for Cosmic Order.

  15. PREFACE: 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare2015)

    NASA Astrophysics Data System (ADS)

    Vlachos, Dimitrios; Vagenas, Elias C.

    2015-09-01

    The 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place in Mykonos, Greece, from Friday 5th June to Monday 8th June 2015. The Conference was attended by more than 150 participants and hosted about 200 oral, poster, and virtual presentations. There were more than 600 pre-registered authors. The 4th IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather intense as after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with a high quality of talks creating an innovative and productive scientific environment for all attendees. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

  16. Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.

    PubMed

    Dutra, Walderez O; Correa-Oliveira, Rodrigo; Dunne, David; Cecchini, Luiza Fosenca; Fraga, Lúcia; Roberts, Morven; Soares-Silveira, Alda Maria; Webster, Michelle; Yssel, Hans; Gollob, Kenneth J

    2002-07-06

    Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-gamma or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-gamma.

  17. Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients

    PubMed Central

    Dutra, Walderez O; Correa-Oliveira, Rodrigo; Dunne, David; Cecchini, Luiza Fosenca; Fraga, Lúcia; Roberts, Morven; Soares-Silveira, Alda Maria; Webster, Michelle; Yssel, Hans; Gollob, Kenneth J

    2002-01-01

    Background Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-γ or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. Results Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. Conclusions High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-γ. PMID:12100735

  18. Oral immunization with F4 fimbriae and CpG formulated with carboxymethyl starch enhances F4-specific mucosal immune response and modulates Th1 and Th2 cytokines in weaned pigs.

    PubMed

    Delisle, Benjamin; Calinescu, Carmen; Mateescu, Mircea Alexandru; Fairbrother, John Morris; Nadeau, Éric

    2012-01-01

    F4 fimbriae are a potential candidate for an oral subunit vaccine for prevention of post-weaning diarrhea in swine due to infection with F4-positive enterotoxigenic Escherichia coli. However, large quantities of F4 fimbriae are required to induce a specific antibody response. The aim of the present study was to evaluate the effect of supplementation of F4 fimbriae with Cytosine-phosphate-Guanosine-oligodeoxynucleotide (CpG-A D19) or with complete cholera toxin (CT) as adjuvants on the F4-specific antibody response and cytokine production in weaned pigs following oral administration of F4 fimbrial antigen formulated with Carboxymethyl Starch (CMS). Oral dosage forms of F4 fimbriae alone or supplemented with CpG-A D19 or with CT were formulated with CMS as monolithic tablets, obtained by direct compression, and administered to weaned pigs. Blood and faecal samples were collected to determine the systemic and mucosal immune status of animals at various times until necropsy. During necropsy, contents of the jejunum and ileum were collected for determination of mucosal F4 specific antibodies. Segments of jejunum and ileum were also used to measure mRNA cytokine production. The presence of CpG in the formulation of the fimbriae significantly increased F4-specific immunoglobulin (Ig) IgM and IgG levels in intestinal secretions, and enhanced Th1 (Interferon-gamma / IFN-γ, Tumour Necrosis Factor-alpha / TNF-α, Interleukin-12p40 / IL-12p40, IL-1β) and Th2 (IL-4, IL-6) cytokine production in intestinal tissues. Supplementation with CT did not result in induction of F4-specific antibodies in secretions, although a significant Th1 response (IFN-α, IFN-γ, IL-18) was detected in tissues. Neither F4-specific systemic antibodies, nor intestinally secreted IgA were detected throughout the immunization trial for all groups. CpG-A D19 appeared to be a promising adjuvant for an oral F4 subunit vaccine formulated with CMS excipient as monolithic tablets. This matrix afforded gastro

  19. Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T cell subsets in multiple sclerosis patients.

    PubMed

    Sacramento, Priscila M; Monteiro, Clarice; Dias, Aleida S O; Kasahara, Taissa M; Ferreira, Thaís B; Hygino, Joana; Wing, Ana Cristina; Andrade, Regis M; Rueda, Fernanda; Sales, Marisa C; Vasconcelos, Claudia Cristina; Bento, Cleonice A M

    2018-05-02

    Excessive levels of pro-inflammatory cytokines in the central nervous system (CNS) are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with multiple sclerosis (MS), a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients. Additionally, 5-HT reduced IFN-γ and IL-17 release by CD8 + T-cells. By contrast, 5-HT increased IL-10 production by CD4 + T-cells from MS patients. A more accurate analysis of these IL-10-secreting CD4 + T-cells revealed that 5-HT favors the expansion of FoxP3 + CD39 + regulatory T cells (Tregs) and type 1 regulatory T cells. Notably, this neurotransmitter also elevated the frequency of Treg17 cells, a novel regulatory T-cell subset. The effect of 5-HT in up-regulating CD39 + Treg and Treg17 cells was inversely correlated with the number of active brain lesions. Finally, in addition to directly reducing cytokine production by purified Th1 and Th17 cells, 5-HT enhanced in vitro Treg function. In summary, our data suggest that serotonin may play a protective role in the pathogenesis of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Report of the 4th Workshop for Technology Transfer for Intelligent Compaction Consortium.

    DOT National Transportation Integrated Search

    2016-03-01

    On October 2728, 2015, the Kentucky Transportation Cabinet (KYTC) hosted the 4th workshop for : the Technology Transfer for Intelligent Compaction Consortium (TTICC), a Transportation Pooled Fund : (TPF5(233)) initiative designed to identify, s...

  1. Pinus densiflora bark extract ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice by regulating Th1/Th2 balance and skin barrier function.

    PubMed

    Lee, Jun Woo; Wu, Qianwen; Jang, Young Pyo; Choung, Se Young

    2018-06-01

    Korean red pine (Pinus densiflora) bark has been traditionally used in Korea and other parts of East Asia to relieve inflammatory diseases. Although many studies using P. densiflora bark have been reported, its effect on atopic dermatitis (AD) has not been elucidated. Thus, we investigated whether the P. densiflora bark extract (PBE) has potential to attenuate AD symptoms and elucidated the molecular mechanism. Oral administration of PBE to mice with 2,4-dinitrochlorobenzene (DNCB)-induced AD lessened dermatitis scores and scratching behavior and significantly reduced measures of epidermal thickness, infiltration of mast cells and eosinophils, levels of immunoglobulin E (IgE), and IgG 1 /IgG 2a ratio in serum. PBE not only inhibited IL-4, IL-5, and IL-13 but also increased IFN-γ in splenic production. Furthermore, PBE significantly suppressed mRNA expression of thymic stromal lymphopoietin and further downregulated the mRNA expression of Th2 and Th17 cytokines such as IL-4, IL-13, IL-17, IL-31, and TNF-α. In addition, the protein expressions of filaggrin, involucrin, and loricrin in lesional skin were recovered by PBE. These results suggest that PBE attenuates DNCB-induced AD via regulating Th1/Th2 balance and skin barrier function. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Chemical and structural evolution in the Th-SeO3(2-)/SeO4(2-) system: from simple selenites to cluster-based selenate compounds.

    PubMed

    Xiao, Bin; Langer, Eike; Dellen, Jakob; Schlenz, Hartmut; Bosbach, Dirk; Suleimanov, Evgeny V; Alekseev, Evgeny V

    2015-03-16

    While extensive success has been gained in the structural chemistry of the U-Se system, the synthesis and characterization of Th-based Se structures are widely unexplored. Here, four new Th-Se compounds, α-Th(SeO3)2, β-Th(SeO3)2, Th(Se2O5)2, and Th3O2(OH)2(SeO4)3, have been obtained from mild hydrothermal or low-temperature (180-220 °C) flux conditions and were subsequently structurally and spectroscopically characterized. The crystal structures of α-Th(SeO3)2 and β-Th(SeO3)2 are based on ThO8 and SeO3 polyhedra, respectively, featuring a three-dimensional (3D) network with selenite anions filling in the Th channels along the a axis. Th(Se2O5)2 is a 3D framework composed of isolated ThO8 polyhedra interconnected by [Se2O5](2-) dimers. Th3O2(OH)2(SeO4)3 is also a 3D framework constructed by octahedral hexathorium clusters [Th6(μ3-O)4(μ3-OH)4](12+), which are interlinked by selenate groups SeO4(2-). The positions of the vibrational modes associated with both Se(IV)O3(2-) and Se(VI)O4(2-) units, respectively, were determined for four compounds, and the Raman spectra of α- and β-Th(SeO3)2 are compared and discussed in detail.

  3. Summary of the 4th Nordic Symposium on Digital Pathology.

    PubMed

    Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

    2017-01-01

    The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4 th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration.

  4. Summary of the 4th Nordic Symposium on Digital Pathology

    PubMed Central

    Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

    2017-01-01

    The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration. PMID:28382222

  5. Fast and Analytical EAP Approximation from a 4th-Order Tensor.

    PubMed

    Ghosh, Aurobrata; Deriche, Rachid

    2012-01-01

    Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data.

  6. Thermodynamic study of the gaseous thorium carbides, ThC, ThC/sub 2/, ThC/sub 3/, ThC/sub 4/, ThC/sub 5/, and ThC/sub 6/

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gupta, S.K.; Gingerich, K.A.

    Six gaseous carbides of thorium, ThC/sub n/(n=1--6), have been identified in a Knudsen effusion mass spectrometric investigation of the vapor phase above a thorium--uranium--rhodium--graphite system at high temperatures. The partial pressures of the thorium containing species were measured as a function of temperature in the 2300--2700 /sup 0/K range. Third law enthalpies for the reactions Th(g)+nC(graphite) =ThC/sub n/, n=1 to 6, and of various other homogeneous and heterogeneous reactions were evaluated. By combining the experimental enthalpies with appropriate thermodynamic data taken from literature, the following values for the atomization energies ..delta..H /sup 0//sub at,298/, and standard heats of formation ..delta..H/supmore » tsdegree//sub f/,298 of thorium carbides have been derived:« less

  7. The α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system.

    PubMed

    Baranowska, Urszula; Wiśniewska, Róża Julia

    2017-07-30

    α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein), are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

  8. Assessing the Organization and Capabilities of 4th Marine Logistics Group

    DTIC Science & Technology

    2010-05-14

    Logistics Group (MLG) should adopt further organizational changes within specific parameters to complement the structure and capabilities of the Active...In order to enhance operational effectiveness and continue its mandated responsibility to augment and reinforce, 4th MLG should adopt further...of the Deputy Commandant, Installations and Logistics (DC, I&L), Marine Forces Reserve ( MFR ), and the MLGs. The paper also relies heavily on the

  9. Effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4⁺ CD25⁺ Foxp3⁺ Treg in asthma Balb/c mouse.

    PubMed

    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.

  10. Outcomes following surgical repair using layered closure of unrepaired 4th degree perineal tear in rural western Uganda.

    PubMed

    Goh, Judith T W; Tan, Stephanie B M; Natukunda, Harriet; Singasi, Isaac; Krause, Hannah G

    2016-11-01

    In many rural low-income countries, perineal tears at time of vaginal birth are not repaired at time of delivery. The aims of this study are to describe the surgical technique for management of the unrepaired 4th degree tear, performed without flaps, and short-term follow up on anal incontinence symptoms using a validated questionnaire. Women presenting to fistula camps in western Uganda with unrepaired 4th degree tears were interviewed using the Cleveland Clinic Continence Score. Interviews were undertaken pre-operatively, at 4-6 weeks post-operatively and 12 months following surgery. Repair of the 4th degree tear was performed in layers, with an overlapping anal sphincter repair and reconstruction of the perineal body, without flaps. All women were examined prior to discharge. 68 women completed pre-operative Cleveland Clinic Continence Scores. Prior to surgery, 59 % of women complained of daily incontinence to solid stools. Over 70 % of women complained of restriction to lifestyle due to the unrepaired 4th degree tear. About 50 % of the women are rejected by their husbands because of the condition. Only 1 woman had wound breakdown on Day 2. At 4 to 6 weeks follow-up, 61 women were contacted and all reported perfect continence. This study highlights the hidden problem of unrepaired 4th degree tears in rural areas of low-income countries where most deliveries are undertaken in the village without professional health care workers. These tears have significant impact on quality of life and anal incontinence. Short-term outcomes following surgical repair using a layered closure are promising.

  11. Suppressive effects of a novel CC chemokine receptor 4 antagonist on Th2 cell trafficking in ligand- and antigen-induced mouse models.

    PubMed

    Komiya, Takaki; Sugiyama, Tetsuya; Takeda, Kazuhiko; Watanabe, Noriki; Imai, Masamichi; Kokubo, Masaya; Tokuda, Natsuko; Ochiai, Hiroshi; Habashita, Hiromu; Shibayama, Shiro

    2013-11-15

    CC chemokine receptor 4 (CCR4) has been implicated as a preferential marker for T helper type 2 (Th2) cells, and is believed to be involved in the pathology of allergic diseases by controlling Th2 cell trafficking into inflamed tissues. The objective of the study was to characterize the pharmacological properties of E0001-163, a novel CCR4 antagonist. E0001-163 was tested in both in vitro chemotaxis assays as well as in vivo mouse models of CCR4 ligand-induced air pouch and antigen-induced airway inflammation by utilizing in vitro-polarized Th2 cells. In vitro, E0001-163 inhibited migratory response of human Th2-polarized cells to CCL22, a CCR4 ligand, with an IC50 value of 11.9 nM. E0001-163 significantly suppressed CCL22-induced Th2 cell trafficking into mouse air pouch in a dose-dependent manner at doses of 3 and 10mg/kg, suggesting that E0001-163 has an inhibitory effect on CCR4-mediated T cell trafficking in vivo. In addition, E0001-163 partially decreased Th2 cell trafficking and the level of IL-4 in the lungs in Th2-tansferred and ovalbumin (OVA)-challenged mice. T cell trafficking involves multiple chemokine receptors both in acute and chronic phases, and our findings suggest that CCR4, together with other chemokine receptors, may be involved in Th2 cell trafficking under disease conditions. © 2013 Elsevier B.V. All rights reserved.

  12. 4th Generation ECR Ion Sources

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lyneis, Claude M.; Leitner, D.; Todd, D.S.

    2008-12-01

    The concepts and technical challenges related to developing a 4th generation ECR ion source with an RF frequency greater than 40 GHz and magnetic confinement fields greater than twice Becr will be explored in this paper. Based on the semi-empirical frequency scaling of ECR plasma density with the square of operating frequency, there should be significant gains in performance over current 3rd generation ECR ion sources, which operate at RF frequencies between 20 and 30 GHz. While the 3rd generation ECR ion sources use NbTi superconducting solenoid and sextupole coils, the new sources will need to use different superconducting materialsmore » such as Nb3Sn to reach the required magnetic confinement, which scales linearly with RF frequency. Additional technical challenges include increased bremsstrahlung production, which may increase faster than the plasma density, bremsstrahlung heating of the cold mass and the availability of high power continuous wave microwave sources at these frequencies. With each generation of ECR ion sources, there are new challenges to be mastered, but the potential for higher performance and reduced cost of the associated accelerator continue to make this a promising avenue for development.« less

  13. Potential pathogenetic role of Th17, Th0, and Th2 cells in erosive and reticular oral lichen planus.

    PubMed

    Piccinni, M-P; Lombardelli, L; Logiodice, F; Tesi, D; Kullolli, O; Biagiotti, R; Giudizi, Mg; Romagnani, S; Maggi, E; Ficarra, G

    2014-03-01

    The role of Th17 cells and associated cytokines was investigated in oral lichen planus. 14 consecutive patients with oral lichen planus were investigated. For biological studies, tissues were taken from reticular or erosive lesions and from normal oral mucosa (controls) of the same patient. mRNA expression for IL-17F, IL-17A, MCP-1, IL-13, IL-2, IL-10, IL-1β, RANTES, IL-4, IL-12B, IL-8, IFN-γ, TNF-α, IL-1α, IL-18, TGF-β1, IL-23R, IL-7, IL-15, IL-6, MIG, IP-10, LTB, VEGF, IL-5, IL-27, IL-23A, GAPDH, PPIB, Foxp3, GATA3, and RORC was measured using the QuantiGene 2.0. Results showed that Th17-type and Th0-type molecules' mRNAs, when compared with results obtained from tissue controls, were increased in biopsies of erosive lesions, whereas Th2-type molecules' mRNAs were increased in reticular lesions. When the CD4+ T-cell clones, derived from oral lichen planus tissues and tissue controls, were analyzed, a higher prevalence of Th17 (confirmed by an increased CD161 expression) and Th0 CD4+ T clones was found in erosive lesions, whereas a prevalence of Th2 clones was observed in reticular lesions. Our data suggest that Th17, Th0, and Th2 cells, respectively, may have a role in the pathogenesis of erosive and reticular oral lichen planus. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Effect of the SQ4R Technique on the Reading Comprehension of Elementary School 4th Grade Elementary School Students

    ERIC Educational Resources Information Center

    Basar, Murat; Gürbüz, Mehmet

    2017-01-01

    The aim of this study is to examine the effect of SQ4R (Survey, Question, Read, Reflect, Recite, Review) technique of the reading comprehension ability of elementary school 4th grade students. The sampling was constituted by 57 students from two different branches of the Ataturk Elementary School in the center of Usak region during the 2nd…

  15. α4+β7hiCD4+ Memory T cells Harbor Most Th-17 cells and are Preferentially Infected During Acute SIV Infection

    PubMed Central

    Kader, Muhamuda; Wang, Xiaolei; Piatak, Michael; Lifson, Jeffrey; Roederer, Mario; Veazey, Ronald; Mattapallil, Joseph J.

    2009-01-01

    HIV/SIV are thought to infect minimally activated CD4+ T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4+ T cells that express high levels of the α4β7 heterodimer are preferentially infected very early during the course of SIV infection. At day 2–4 post infection, α4+β7hiCD4+ T cells had ∼ 5x more SIV-gag DNA than β7−CD4+ T cells. α4+β7hiCD4+ T cells displayed a predominantly central memory (CD45RA−CD28+CCR7+) and resting (CD25−CD69−HLA-DR−Ki-67−) phenotype. Though the expression of detectable CCR5 was variable on α4+β7hi and β7−CD4+ T cells, both CCR5+ and CCR5− subsets of α4+β7hi and β7−CD4+ T cells were found to express sufficient levels of CCR5 mRNA suggesting that both these subsets could be efficiently infected by SIV. In line with this, we found similar levels of SIV infection in β7−CD4+CCR5+ and β7−CD4+CCR5− T cells. α4β7hiCD4+ T cells were found to harbor most Th-17 cells that were significantly depleted during acute SIV infection. Taken together, our results show that resting memory α4+β7hiCD4+ T cells in blood are preferentially depleted during acute SIV infection, and the loss of these cells alters the balance between Th-17 and Th-1 responses thereby contributing to disease pathogenesis. PMID:19571800

  16. Adsorption characteristics of UO(2)(2+) and Th(4+) ions from simulated radioactive solutions onto chitosan/clinoptilolite sorbents.

    PubMed

    Humelnicu, Doina; Dinu, Maria Valentina; Drăgan, Ecaterina Stela

    2011-01-15

    Adsorption features of UO(2)(2+) and Th(4+) ions from simulated radioactive solutions onto a novel chitosan/clinoptilolite (CS/CPL) composite as beads have been investigated compared with chitosan cross-linked with epichlorohydrin. The effects of contact time, the initial metal ion concentration, sorbent mass and temperature on the adsorption capacity of the CS-based sorbents were investigated. The adsorption kinetics was well described by the pseudo-second order equation, and the adsorption isotherms were better fitted by the Sips model. The maximum experimental adsorption capacities were 328.32 mg Th(4+)/g composite, and 408.62 mg UO(2)(2+)/g composite. The overall adsorption tendency of CS/CPL composite toward UO(2)(2+) and Th(4+) radiocations in the presence of Cu(2+), Fe(2+) and Al(3+), under competitive conditions, followed the order: Cu(2+)>UO(2)(2+)>Fe(2+)>Al(3+), and Cu(2+)>Th(4+)>Fe(2+)>Al(3+), respectively. The negative values of Gibbs free energy of adsorption indicated the spontaneity of the adsorption of radioactive ions on both the CS/CPL composite and the cross-linked CS. The desorption level of UO(2)(2+) from the composite CS/CPL, by using 0.1M Na(2)CO(3), was around 92%, and that of Th(4+) ions, performed by 0.1M HCl, was around 85%, both values being higher than the desorption level of radiocations from the cross-linked CS, which were 89% and 83%, respectively. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites.

    PubMed

    Vestal, Heather S; Belitsky, Richard; Bernstein, Carol A; Chaukos, Deanna; Cohen, Mitchell B; Dickstein, Leah J; Hilty, Donald M; Hutner, Lucy; Sakman, Ferda; Scheiber, Stephen C; Wrzosek, Marika I; Silberman, Edward K

    2016-10-01

    The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. We reviewed the websites of all 193 2014-2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training.

  18. Fast and Analytical EAP Approximation from a 4th-Order Tensor

    PubMed Central

    Ghosh, Aurobrata; Deriche, Rachid

    2012-01-01

    Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data. PMID:23365552

  19. 76 FR 33157 - Safety Zones; July 4th Fireworks Displays Within the Captain of the Port Miami Zone, FL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0439] RIN 1625-AA00 Safety Zones; July 4th Fireworks Displays Within the Captain of the Port Miami Zone, FL AGENCY...-0439 Safety Zones; July 4th Fireworks Displays within the Captain of the Port Miami Zone, FL. (a...

  20. APTWG: The 4th Asia-Pacific Transport Working Group Meeting

    NASA Astrophysics Data System (ADS)

    Ida, K.; Kwon, J. M.; Leconte, M.; Ko, W. H.; Inagaki, S.; Todo, Y.; Kosuga, Y.

    2015-01-01

    This conference report summarizes the contributions to, and discussions at, the 4th Asia-Pacific Transport Working Group Meeting held at Kyushu University, Japan, during 10-13 June 2014. The topics of the meeting were organized under five main headings: turbulence suppression and transport barrier formation, effect of magnetic topology on MHD activity and transport, non-diffusive contribution of momentum and particle transport, non-local transport and turbulence spreading and coupling, energetic particles and instability. The Young Researchers' Forum which was held in this meeting is also described in this report.

  1. 75 FR 38723 - Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ...-AA00 Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI AGENCY... safety zone on East Moran Bay, Lake Huron, St. Ignace, Michigan. This zone is intended to restrict vessels from a portion of East Moran Bay during the St. Ignace 4th of July Fireworks display, July 4, 2010...

  2. 78 FR 23869 - Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ...-AA00 Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA... establish a temporary safety zone in the navigable waters of the Port of Redwood City near Redwood City, CA in support of the Redwood City 4th of July Fireworks Show on July 4, 2013. This safety zone is...

  3. Strengthening of the Coordination Shell by Counter Ions in Aqueous Th 4+ Solutions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Atta-Fynn, Raymond; Bylaska, Eric J.; de Jong, Wibe A.

    The presence of counter ions in solutions containing highly charged metal cations can trigger processes such as ion-pair formation, hydrogen bond breakages and subsequent reformation, and ligand exchanges. In this work, it is shown how halide (Cl-, Br-) and perchlorate (ClO4-) anions affect the strength of the primary solvent coordination shells around Th4+ using explicit solvent and finite temperature ab initio molecular dynamics modeling methods. The 9-fold solvent geometry was found to be the most stable hydration structure in each aqueous solution. Relative to the dilute aqueous solution, the presence of the counter ions did not significantly alter the geometrymore » of the primary hydration shell. However, the free energy analyses indicated that the 10-fold hydrated states were thermodynamically accessible in dilute and bromide aqueous solutions within 1 kcal/mol. Analysis of the results showed that the hydrogen bond lifetimes were longer and solvent exchange energy barriers were larger in solutions with counter ions in comparison with the solution with no counter ions. This implies that the presence of the counter ions induces a strengthening of the Th4+ hydration shell.« less

  4. Groupwise Registration and Atlas Construction of 4th-Order Tensor Fields Using the ℝ+ Riemannian Metric*

    PubMed Central

    Barmpoutis, Angelos

    2010-01-01

    Registration of Diffusion-Weighted MR Images (DW-MRI) can be achieved by registering the corresponding 2nd-order Diffusion Tensor Images (DTI). However, it has been shown that higher-order diffusion tensors (e.g. order-4) outperform the traditional DTI in approximating complex fiber structures such as fiber crossings. In this paper we present a novel method for unbiased group-wise non-rigid registration and atlas construction of 4th-order diffusion tensor fields. To the best of our knowledge there is no other existing method to achieve this task. First we define a metric on the space of positive-valued functions based on the Riemannian metric of real positive numbers (denoted by ℝ+). Then, we use this metric in a novel functional minimization method for non-rigid 4th-order tensor field registration. We define a cost function that accounts for the 4th-order tensor re-orientation during the registration process and has analytic derivatives with respect to the transformation parameters. Finally, the tensor field atlas is computed as the minimizer of the variance defined using the Riemannian metric. We quantitatively compare the proposed method with other techniques that register scalar-valued or diffusion tensor (rank-2) representations of the DWMRI. PMID:20436782

  5. CD4+CD25+ Regulatory Cells Contribute to the Regulation of Colonic Th2 Granulomatous Pathology Caused by Schistosome Infection

    PubMed Central

    Turner, Joseph D.; Jenkins, Gavin R.; Hogg, Karen G.; Aynsley, Sarah A.; Paveley, Ross A.; Cook, Peter C.; Coles, Mark C.; Mountford, Adrian P.

    2011-01-01

    Eggs of the helminth Schistosoma mansoni accumulate in the colon following infection and generate Th2-biassed inflammatory granulomas which become down- modulated in size as the infection proceeds to chronicity. However, although CD4+CD25+FoxP3+regulatory T cells (Tregs) are known to suppress Th1-mediated colitis, it is not clear whether they control Th2 –associated pathologies of the large intestine which characterise several helminth infections. Here we used a novel 3D-multiphoton confocal microscopy approach to visualise and quantify changes in the size and composition of colonic granulomas at the acute and chronic phases of S. mansoni infection. We observed decreased granuloma size, as well as reductions in the abundance of DsRed+ T cells and collagen deposition at 14 weeks (chronic) compared to 8 weeks (acute) post-infection. Th2 cytokine production (i.e. IL-4, IL-5) in the colonic tissue and draining mesenteric lymph node (mLN) decreased during the chronic phase of infection, whilst levels of TGF-β1 increased, co-incident with reduced mLN proliferative responses, granuloma size and fibrosis. The proportion of CD4+CD25+FoxP3+Tregs: CD4+ cells in the mLN increased during chronic disease, while within colonic granulomas there was an approximate 4-fold increase. The proportion of CD4+CD25+FoxP3+Tregs in the mLN that were CD103+ and CCR5+ also increased indicating an enhanced potential to home to intestinal sites. CD4+CD25+ cells suppressed antigen-specific Th2 mLN cell proliferation in vitro, while their removal during chronic disease resulted in significantly larger granulomas, partial reversal of Th2 hypo-responsiveness and an increase in the number of eosinophils in colonic granulomas. Finally, transfer of schistosome infection-expanded CD4+CD25+Tregs down-modulated the development of colonic granulomas, including collagen deposition. Therefore, CD4+CD25+FoxP3+Tregs appear to control Th2 colonic granulomas during chronic infection, and are likely to play a

  6. The Effect of the Thinking-Aloud Strategy on the Reading Comprehension Skills of 4th Grade Primary School Students

    ERIC Educational Resources Information Center

    Sönmez, Yasemin; Sulak, Süleyman Erkam

    2018-01-01

    The purpose of this study, which is designed in quasi-experimental model, is to examine the effect of the thinking aloud strategy on the reading comprehension skills of the 4th grade primary school students. For this purpose, in the second semester of 2016-2017 academic year, the reading comprehension levels of 26 students in the 4th grade at a…

  7. 4th International Symposium on Autophagy: exploiting the frontiers of autophagy research.

    PubMed

    Eskelinen, Eeva-Liisa; Deretic, Vojo; Neufeld, Thomas; Levine, Beth; Cuervo, Ana Maria

    2007-01-01

    The 4th International Symposium on Autophagy was held in Mishima, a small town between Tokyo and Kyoto, October 1-5, 2006 (http://isa4th.umin.jp/). The meeting was organized by the group of Eiki Kominami. Approximately 150 participants took part in this well-organized meeting in the spacious and comfortable Toray Conference Hall (Fig. 1). The social program offered opportunities for informal discussions, Japanese culture (from karaoke singing to traditional drumming; Fig. 2), history and nature (a visit to a steaming volcano; Fig. 3), as well as delicious Japanese food. The scientific program started with two plenary lectures on Sunday evening. Daniel Klionsky gave an overview of Atg9 cycling in yeast and Shigekazu Nagata talked about apoptosis and engulfment of dead cells by macrophages. The meeting consisted of five oral sessions and two poster sessions covering a wide range of autophagy-related topics. Exciting unpublished results were presented in all sessions, showing how quickly autophagy research is progressing. Two themes were discussed in many sessions during the symposium: the role of autophagy in the degradation of aggregate-prone proteins and protein aggregates, and the possible role of p62 in autophagy.

  8. 4th Annual Predictive Toxicology Summit 2012.

    PubMed

    Cui, Zhanfeng

    2013-08-01

    This meeting report presents a brief summary on the 4th Annual Predictive Toxicology Summit 2012, which was held on 15 - 16 February 2012 in London. The majority of presentations came from global pharmaceutical companies, although small and medium enterprise (SME) and academic researchers were represented too. Major regulatory bodies were also present. The article highlights the summit, which was considered a good learning opportunity to catch up on the recent advances in predictive toxicology. Predictive toxicology has become more and more important due to social and economic pressure and scientific reasons. Technological developments are rapid, but there is a gulf between the technology developers and the pharmaceutical end users; hence, early engagement is desirable. Stem cell-derived cell-based assays as well as three-dimensional in vitro tissue/organ model development are within the reach now, but a lot needs to be done to optimise and validate the developed protocols and products. The field of predictive toxicology needs fundamental research of interdisciplinary nature, which requires much needed trained personnel and funding.

  9. 4th European Seminars in Virology on Oncogenic and Oncolytic Viruses, in Bertinoro (Bologna), Italy.

    PubMed

    Reale, Alberto; Messa, Lorenzo; Vitiello, Adriana; Loregian, Arianna; Palù, Giorgio

    2017-10-01

    The 4th European Seminars in Virology (EuSeV), which was focused on oncogenic and oncolytic viruses, was held in Bertinoro (Bologna), Italy, from June 10 to 12, 2016. This article summarizes the plenary lectures and aims to illustrate the main topics discussed at 4th EuSeV, which brought together knowledge and expertise in the field of oncogenic and oncolytic viruses from all over the world. The meeting was divided in two parts, "Mechanisms of Viral Oncogenesis" and "Viral Oncolysis and Immunotherapy," which were both focused on dissecting the complex and multi-factorial interplay between cancer and human viruses and on exploring new anti-cancer strategies. J. Cell. Physiol. 232: 2641-2648, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. International consensus on military research priorities and gaps - Survey results from the 4th International Congress on Soldiers' Physical Performance.

    PubMed

    Lovalekar, Mita; Sharp, Marilyn A; Billing, Daniel C; Drain, Jace R; Nindl, Bradley C; Zambraski, Edward J

    2018-06-06

    The objectives of this study were to identify perceived priorities related to military personnel's health and physical performance, among attendees at the 4th International Congress on Soldiers' Physical Performance (ICSPP), and to determine if perceived priorities had changed between the 3rd ICSPP survey held in 2014 and the 4th ICSPP survey held in 2017. Electronic survey. Respondents were asked to grade priority areas on a Likert scale, and average ratings were used to rank priority areas. Responses to free text questions were analyzed qualitatively. Responses to the 4th ICSPP survey were described and compared to responses to the 3rd ICSPP survey. The 4th ICSPP survey respondents were a diverse group (40.6% military, 58.9% civilian). The two most important priority areas identified were physical demands in operational environments (mean score=4.41/5) and measuring physical performance/fitness (4.38/5), which were also the top two areas in the 3rd ICSPP survey. There was remarkable overlap in the rankings of priority areas between the two surveys. Sleep and nutrition were emerging priority areas and were perceived as relatively more important in the 4th ICSPP survey compared to the 3rd ICSPP survey. The greatest perceived emerging threat was resilience/psychological fitness of recruits (4.16/5). Physiological status monitoring (2.79/4) was identified as the most important technology. Despite the diverse backgrounds of the respondents, there was a clear continuing consensus about perceived important priority areas influencing military personnel's health and physical performance. Soldier resiliency and assessment of physiological status were research topics identified as top priorities. Copyright © 2018 Sports Medicine Australia. All rights reserved.

  11. Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells

    PubMed Central

    Ogasawara, Takashi; Kohashi, Yuko; Ikari, Jun; Taniguchi, Toshibumi; Tsuruoka, Nobuhide; Watanabe-Takano, Haruko; Fujimura, Lisa; Sakamoto, Akemi; Hatano, Masahiko; Hirata, Hirokuni; Fukushima, Yasutsugu; Fukuda, Takeshi; Kurasawa, Kazuhiro; Tatsumi, Koichiro; Tokuhisa, Takeshi; Arima, Masafumi

    2018-01-01

    Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. PMID:29696026

  12. Two actinide-organic frameworks constructed by a tripodal flexible ligand: Occurrence of infinite {(UO2)O2(OH)3}4n and hexanuclear {Th6O4(OH)4} motifs

    NASA Astrophysics Data System (ADS)

    Liang, Lingling; Zhang, Ronglan; Zhao, Jianshe; Liu, Chiyang; Weng, Ng Seik

    2016-11-01

    Two new actinide metal-organic frameworks were constructed by using a tripodal flexible ligand tris (2-carboxyethyl) isocyanurate (H3tci) under hydrothermal condition. The combination of H3tci and uranyl nitrate hexahydrate in aqueous solution leads to the isolation of [(UO2)2(H2O)4]0.5(tci)2(UO2)4(OH)4·18H2O (1), which contains two distinct UO22+ coordination environments. Four uranyl cations, linked through μ3-OH respectively, result in the edge-sharing ribbons. Then, the layer structure is constructed by U-O clusters linked through other eight-coordinated uranyl unions, giving rise to a porous structure in the space. Topological analysis reveals that complex 1 belongs to a (4, 8)-connected net with a schläfli symbol of (34.26.3)2(34.46.56.68.73.8). Th3(tci)2O2(OH)2(H2O)3·12H2O (2) generated by the reaction of H3tci and thorium nitrate tetrahydrate, possesses nine-fold coodinated Th(IV) centers with a monocapped square antiprismatic geometry. The hexamers "Th6O4(OH)4" motifs are connected together by the carboxylate groups, showing a three-dimensional structures. Complex 2 takes on an 8-connected architecture and the point symbol is (424.64).

  13. IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

    PubMed

    Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

    2017-10-01

    IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Ar-40/Ar-39 and U-Th-Pb dating of separated clasts from the Abee E4 chondrite

    NASA Technical Reports Server (NTRS)

    Bogard, D. D.; Unruh, D. M.; Tatsumoto, M.

    1983-01-01

    Ar-40/Ar-39 and U-Th-Pb are investigated for three clasts from the Abee (E4) enstatite chondrite, yielding Ar-40/Ar-39 plateau ages (and/or maximum ages) of 4.5 Gy, while two of the clasts give average ages of 4.4 Gy. The 4.4-4.5 Gy range does not resolve possible age differences among the clasts. The U-Th-Pb data are consistent with the interpretation that initial clast formation occurred 4.58 Gy ago, and that the clasts have since remained closed systems which have been contaminated with terrestrial Pb. The thermal history of Abee deduced from Ar data seems consistent with that deduced from magnetic data, suggesting that various Abee components experienced separate histories until brecciation no later than 4.4 Gy ago, experiencing no significant subsequent heating.

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

    PubMed

    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

  16. TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging.

    PubMed

    Peeters, Sarah G J A; Zegers, Catharina M L; Biemans, Rianne; Lieuwes, Natasja G; van Stiphout, Ruud G P M; Yaromina, Ala; Sun, Jessica D; Hart, Charles P; Windhorst, Albert D; van Elmpt, Wouter; Dubois, Ludwig J; Lambin, Philippe

    2015-07-01

    Conventional anticancer treatments are often impaired by the presence of hypoxia. TH-302 selectively targets hypoxic tumor regions, where it is converted into a cytotoxic agent. This study assessed the efficacy of the combination treatment of TH-302 and radiotherapy in two preclinical tumor models. The effect of oxygen modification on the combination treatment was evaluated and the effect of TH-302 on the hypoxic fraction (HF) was monitored using [(18)F]HX4-PET imaging and pimonidazole IHC stainings. Rhabdomyosarcoma R1 and H460 NSCLC tumor-bearing animals were treated with TH-302 and radiotherapy (8 Gy, single dose). The tumor oxygenation status was altered by exposing animals to carbogen (95% oxygen) and nicotinamide, 21% or 7% oxygen breathing during the course of the treatment. Tumor growth and treatment toxicity were monitored until the tumor reached four times its start volume (T4×SV). Both tumor models showed a growth delay after TH-302 treatment, which further increased when combined with radiotherapy (enhancement ratio rhabdomyosarcoma 1.23; H460 1.49). TH-302 decreases the HF in both models, consistent with its hypoxia-targeting mechanism of action. Treatment efficacy was dependent on tumor oxygenation; increasing the tumor oxygen status abolished the effect of TH-302, whereas enhancing the HF enlarged TH-302's therapeutic effect. An association was observed in rhabdomyosarcoma tumors between the pretreatment HF as measured by [(18)F]HX4-PET imaging and the T4×SV. The combination of TH-302 and radiotherapy is promising and warrants clinical testing, preferably guided by the companion biomarker [(18)F]HX4 hypoxia PET imaging for patient selection. ©2015 American Association for Cancer Research.

  17. Th17 cells and CD4(+) multifunctional T cells in patients with systemic lupus erythematosus.

    PubMed

    Araújo, Júlio Antônio Pereira; Mesquita, Danilo; de Melo Cruvinel, Wilson; Salmazi, Karina Inácio; Kallás, Esper Georges; Andrade, Luis Eduardo Coelho

    2016-01-01

    Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i.e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4(+) T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4(+) T cells analyzed. We found that SLE patients presented a decreased number of total CD4(+) cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  18. Breakfast patterns among low-income, ethnically-diverse 4th-6th grade children in an urban area.

    PubMed

    Lawman, Hannah G; Polonsky, Heather M; Vander Veur, Stephanie S; Abel, Michelle L; Sherman, Sandy; Bauer, Katherine W; Sanders, Tim; Fisher, Jennifer O; Bailey-Davis, Lisa; Ng, Janet; Van Wye, Gretchen; Foster, Gary D

    2014-06-14

    Increasing school breakfast participation has been advocated as a method to prevent childhood obesity. However, little is known about children's breakfast patterns outside of school (e.g., home, corner store). Policies that increase school breakfast participation without an understanding of children's breakfast habits outside of school may result in children consuming multiple breakfasts and may undermine efforts to prevent obesity. The aim of the current study was to describe morning food and drink consumption patterns among low-income, urban children and their associations with relative weight. A cross-sectional analysis was conducted of data obtained from 651 4th-6th graders (51.7% female, 61.2% African American, 10.7 years) in 2012. Students completed surveys at school that included all foods eaten and their locations that morning. Height and weight were measured by trained research staff. On the day surveyed, 12.4% of youth reported not eating breakfast, 49.8% reported eating one breakfast, 25.5% reported eating two breakfasts, and 12.3% reported eating three or more breakfasts. The number of breakfasts consumed and BMI percentile showed a significant curvilinear relationship, with higher mean BMI percentiles observed among children who did not consume any breakfast and those who consumed ≥ 3 breakfasts. Sixth graders were significantly less likely to have consumed breakfast compared to younger children. A greater proportion of obese youth had no breakfast (18.0%) compared to healthy weight (10.1%) and overweight youth (10.7%, p = .01). When promoting school breakfast, policies will need to be mindful of both over- and under-consumption to effectively address childhood obesity and food insecurity. NCT01924130 from http://clinicaltrials.gov/.

  19. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

    PubMed

    Tan, Xiahui; Khalil, Najwa; Tesarik, Candice; Vanapalli, Karunasri; Yaputra, Viki; Alkhouri, Hatem; Oliver, Brian G G; Armour, Carol L; Hughes, J Margaret

    2012-04-01

    In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

  20. Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4+CCR6+ Th/Treg cell subset imbalance in ankylosing spondylitis

    PubMed Central

    2011-01-01

    Introduction Ankylosing spondylitis (AS) is a chronic autoimmune disease, and the precise pathogenesis is largely unknown at present. Bone marrow-derived mesenchymal stem cells (BMSCs) with immunosuppressive and anti-inflammatory potential and Th17/Treg cells with a reciprocal relationship regulated by BMSCs have been reported to be involved in some autoimmune disorders. Here we studied the biological and immunological characteristics of BMSCs, the frequency and phenotype of CCR4+CCR6+ Th/Treg cells and their interaction in vitro in AS. Methods The biological and immunomodulation characteristics of BMSCs were examined by induced multiple-differentiation and two-way mixed peripheral blood mononuclear cell (PBMC) reactions or after stimulation with phytohemagglutinin, respectively. The interactions of BMSCs and PBMCs were detected with a direct-contact co-culturing system. CCR4+CCR6+ Th/Treg cells and surface markers of BMSCs were assayed using flow cytometry. Results The AS-BMSCs at active stage showed normal proliferation, cell viability, surface markers and multiple differentiation characteristics, but significantly reduced immunomodulation potential (decreased 68 ± 14%); the frequencies of Treg and Fox-P3+ cells in AS-PBMCs decreased, while CCR4+CCR6+ Th cells increased, compared with healthy donors. Moreover, the AS-BMSCs induced imbalance in the ratio of CCR4+CCR6+ Th/Treg cells by reducing Treg/PBMCs and increasing CCR4+CCR6+ Th/PBMCs, and also reduced Fox-P3+ cells when co-cultured with PBMCs. Correlation analysis showed that the immunomodulation potential of BMSCs has significant negative correlations with the ratio of CCR4+CCR6+ Th to Treg cells in peripheral blood. Conclusions The immunomodulation potential of BMSCs is reduced and the ratio of CCR4+CCR6+ Th/Treg cells is imbalanced in AS. The BMSCs with reduced immunomodulation potential may play a novel role in AS pathogenesis by inducing CCR4+CCR6+ Th/Treg cell imbalance. PMID:21338515

  1. Effectiveness of Web Quest in Enhancing 4th Grade Students' Spiritual Intelligence

    ERIC Educational Resources Information Center

    Jwaifell, Mustafa; Al-Mouhtadi, Reham; Aldarabah, Intisar

    2015-01-01

    Spiritual intelligence has gained great interest from a good number of the researchers and scholars, while there is a lack of using new technologies such as WebQuest as an instructional tool; which is one of the e-learning applications in education in enhancing spiritual intelligence of 4th graders in Jordanian schools. This study aimed at…

  2. The relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips.

    PubMed

    Sönmez, M; Tattemur, Y; Karacan, K; Erdal, M

    2012-08-01

    The angle towards the lateral side between the arm and forearm when the forearm is in full extension and supination is defined as the carrying angle. It is well known that the 2nd finger is longer in women whereas the 4th finger is longer in men, due to in-utero hormonal effects. In the present study, the relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips is studied. The findings reveal that the carrying angle was greater both in left and right sides in women than in men. In addition, while the distal extent of the 2nd fingertips was longer in women, the 4th fingertip was longer in men. There was a moderately positive correlation between the carrying angle and the distal fingertip lengths. Therefore, it could be suggested that the morphometric factors play role on the distal extent of the fingertips other than the hormonal effects.

  3. Symmetric Positive 4th Order Tensors & Their Estimation from Diffusion Weighted MRI⋆

    PubMed Central

    Barmpoutis, Angelos; Jian, Bing; Vemuri, Baba C.; Shepherd, Timothy M.

    2009-01-01

    In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing a 2nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. It is now well known that this 2nd-order approximation fails to approximate complex local tissue structures, such as fibers crossings. In this paper we employ a 4th order symmetric positive semi-definite (PSD) tensor approximation to represent the diffusivity function and present a novel technique to estimate these tensors from the DW-MRI data guaranteeing the PSD property. There have been several published articles in literature on higher order tensor approximations of the diffusivity function but none of them guarantee the positive semi-definite constraint, which is a fundamental constraint since negative values of the diffusivity coefficients are not meaningful. In our methods, we parameterize the 4th order tensors as a sum of squares of quadratic forms by using the so called Gram matrix method from linear algebra and its relation to the Hilbert’s theorem on ternary quartics. This parametric representation is then used in a nonlinear-least squares formulation to estimate the PSD tensors of order 4 from the data. We define a metric for the higher-order tensors and employ it for regularization across the lattice. Finally, performance of this model is depicted on synthetic data as well as real DW-MRI from an isolated rat hippocampus. PMID:17633709

  4. MTORC1 EXPANDS TH17 AND IL-4+ DN T CELLS AND CONTRACTS TREGS IN SLE

    PubMed Central

    Kato, Hiroshi; Perl, Andras

    2014-01-01

    The mechanistic target of rapamycin (mTOR) is activated in CD4−CD8− double-negative (DN) T cells and its blockade is therapeutic in systemic lupus erythematosus (SLE) patients. Murine studies showed the involvement of mTOR complex 1 (mTORC1) and 2 (mTORC2) in the differentiation of Th1/Th17 cells and Th2 cells, respectively. Here, we investigated the roles of mTORC1 and mTORC2 in T-cell lineage development in SLE and matched healthy control (HC) subjects. mTORC1 activity was increased while mTORC2 was reduced as assessed by phosphorylation of their substrates pS6K or pS6RP and pAkt, respectively. Rapamycin inhibited mTORC1 and enhanced mTORC2. IL-4 expression was increased in freshly isolated CD8+ lupus T cells (SLE: 8.09±1.93%, HC: 3.61±0.49%; p=0.01). DN T cells had greater IL-4 expression than CD4+ or CD8+ T cells of SLE patients after 3 day in vitro stimulation, which was suppressed by rapamycin (control: 9.26±1.48%, rapamycin: 5.03±0.66%; p<0.001). GATA-3 expression was increased in CD8+ lupus T cells (p<0.01) and insensitive to rapamycin treatment. IFN-γ expression was reduced in all lupus T cell subsets (p=1.0×10−5) and also resisted rapamycin. IL-17 expression was increased in CD4+ lupus T cells (SLE: 3.62±0.66%, HC: 2.29±0.27%; p=0.019), which was suppressed by rapamycin (control: 3.91±0.79%, rapamycin: 2.22±0.60%; p<0.001). Frequency of Tregs was reduced in SLE (SLE: 1.83±0.25%, HC: 2.97±0.27%; p=0.0012). Rapamycin inhibited mTORC1 in Tregs and promoted their expansion. Neutralization of IL-17 but not IL-4 also expanded Tregs in SLE and HC subjects. These results indicate that mTORC1 expands IL-4+ DN T and Th17 cells and contracts Tregs in SLE. PMID:24683191

  5. Differences in the 2nd to 4th digit length ratio in humans reflect shifts along the common allometric line

    PubMed Central

    Kratochvíl, Lukáš; Flegr, Jaroslav

    2009-01-01

    Ratios often lead to biased conclusions concerning the actual relationships between examined traits and comparisons of the relative size of traits among groups. Therefore, the use of ratios has been abandoned in most comparative studies. However, ratios such as body mass index and waist-to-hip ratio are widely used in evolutionary biology and medicine. One such, the ratio of the 2nd to the 4th finger (2D : 4D), has been the subject of much recent interest in both humans and animals. Most studies agree that 2D : 4D is sexually dimorphic. In men, the 2nd digit tends to be shorter than the 4th, while in women the 2nd digit tends to be of the same size or slightly longer than the 4th. Nevertheless, here we demonstrate that the sexes do not greatly differ in the scaling between the 2nd and 4th digit. Sexual differences in 2D : 4D are mainly caused by the shift along the common allometric line with non-zero intercept, which means 2D : 4D necessarily decreases with increasing finger length, and the fact that men have longer fingers than women. We conclude that previously published results on the 2D : 4D ratio are biased by its covariation with finger length. We strongly recommend regression-based approaches for comparisons of hand shape among different groups. PMID:19553247

  6. Using 4th order Runge-Kutta method for solving a twisted Skyrme string equation

    NASA Astrophysics Data System (ADS)

    Hadi, Miftachul; Anderson, Malcolm; Husein, Andri

    2016-03-01

    We study numerical solution, especially using 4th order Runge-Kutta method, for solving a twisted Skyrme string equation. We find numerically that the value of minimum energy per unit length of vortex solution for a twisted Skyrmion string is 20.37 × 1060 eV/m.

  7. Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients.

    PubMed

    Li, Qifeng; Zhang, Hui; Yu, Liang; Wu, Chao; Luo, Xinhui; Sun, He; Ding, Jianbing

    2018-01-01

    Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and cytokines of IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR or immunoblotting. Our results showed that DAPT effectively inhibited the protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, Th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. In conclusion, our results suggest that blocking Notch signaling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients. Copyright © 2017. Published by Elsevier B.V.

  8. Proceedings of the Seventh International Conference on Educational Data Mining (EDM) (7th, London, United Kingdom, July 4-7, 2014)

    ERIC Educational Resources Information Center

    Stamper, John, Ed.; Pardos, Zachary, Ed.; Mavrikis, Manolis, Ed.; McLaren, Bruce M., Ed.

    2014-01-01

    The 7th International Conference on Education Data Mining held on July 4th-7th, 2014, at the Institute of Education, London, UK is the leading international forum for high-quality research that mines large data sets in order to answer educational research questions that shed light on the learning process. These data sets may come from the traces…

  9. Dietary Fructo-Oligosaccharides Attenuate Early Activation of CD4+ T Cells Which Produce both Th1 and Th2 Cytokines in the Intestinal Lymphoid Tissues of a Murine Food Allergy Model.

    PubMed

    Tsuda, Masato; Arakawa, Haruka; Ishii, Narumi; Ubukata, Chihiro; Michimori, Mana; Noda, Masanari; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

    2017-01-01

    Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated the cellular mechanisms through which FOS modulate intestinal antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice. OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA and FOS for 1 week. Body weight and mucosal mast cell protease 1 in the serum were measured as the indicator of intestinal inflammation. Single-cell suspensions were prepared from intestinal and systemic lymphoid tissues for cellular analysis. Cytokine production was measured by ELISA. Activation markers and intracellular cytokines in CD4+ T cells were analyzed by flow cytometry. Activated CD4+ T cells were purified to examine cytokine production. Dietary intake of FOS provided moderate protection from the intestinal inflammation induced by the OVA-containing diet. FOS significantly reduced food allergy-induced Th2 cytokine responses in intestinal tissues but not in systemic tissues. FOS decreased OVA diet-induced IFN-γ+IL-4+ double-positive CD4+ T cells and early-activated CD45RBhighCD69+CD4+ T cells in the mesenteric lymph nodes. Furthermore, we confirmed that these CD45RBhighCD69+CD4+ T cells are able to produce high levels of IFN-γ and moderate level of IL-4, IL-10, and IL-13. Dietary intake of FOS during the development of food allergy attenuates the induction of intestinal Th2 cytokine responses by regulating early activation of naïve CD4+ T cells, which produce both Th1 and Th2 cytokines. Our results suggest FOS might be a potential food agent for the prevention of food allergy by modulating oral sensitization to food antigens. © 2017 S. Karger AG, Basel.

  10. Electroacupuncture promotes a decrease in inflammatory response associated with Th1/Th2 cytokines, nitric oxide and leukotriene B4 modulation in experimental asthma.

    PubMed

    Carneiro, E R; Xavier, R A N; De Castro, M A Pedreira; Do Nascimento, C M Oller; Silveira, V L F

    2010-06-01

    Previously, we have shown that electroacupuncture (EA) in rats decreased eosinophil infiltration into the pulmonary tissue (PT) and in the bronchoalveolar lavage (BAL) in an experimental model of asthma. Th2 cytokines, leukotriene B4 (LTB4) and nitric oxide (NO) are involved in the asthma inflammatory process. The aim of this study was to verify the effects of EA on these asthma mediators. Male Wistar rats were divided into control (C), immobilized (I), sham acupuncture (SA), and acupuncture (A) groups. All rats were sensitized, and EA treatment using clinical acupuncture points was started 24h after antigen priming. EA was done every other day for 2weeks. Subsequently, animals were challenged by inhalation and sacrificed 24h later. At this time, the BAL and lungs were collected and used to analyze cytokine production, LTB4 and NO. The EA increased IL-1 and IFN-gamma and decreased IL-4, IL-10, NO and LTB4 in the BAL and PT compared to the C and SA groups. The presence of eosinophils in the BAL negatively correlated with IL-1 and IFN-gamma production and positively correlated with IL-4 and IL-10 production. Our results show that the beneficial anti-inflammatory action of EA on asthma is related to the balance of the Thl/Th2 response and the reduction of LTB4 and NO. These results suggest that EA therapy could be an important complementary treatment for asthma. Copyright 2010. Published by Elsevier Ltd.

  11. Aberrant expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice.

    PubMed

    Hwang, Soo Seok; Kim, Kiwan; Lee, Wonyong; Lee, Gap Ryol

    2012-08-03

    The Th2 locus control region (LCR) has been shown to be a crucial cis-acting element for Th2 cytokine expression and Th2 cell differentiation. To study the role of Th2 LCR in ifng locus regulation, we examined the expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice. We found IFN-γ to be aberrantly up-regulated. In addition, histone 3(H3)-acetylation and histone 3 lysine 4 (H3-K4)-methylation greatly increased at the ifng locus of the Th2 cells. GATA-3 and STAT6 bound to the ifng promoter in Th2 cells from the wild type but not from the Th2 LCR-deficient mice, and they directly repressed ifng expression in transient reporter assay. Moreover, ectopic expression of GATA-3 and STAT6-VT repressed the aberrant expression of the ifng gene and restored repressive chromatin state at the ifng locus in Th2 cells from Th2 LCR-deficient mice. These results suggest that expression of the ifng gene and chromatin remodeling of the ifng locus are under the control of a Th2 LCR-mediated Th2 differentiation program. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Transcription factor-dependent chromatin remodeling of Il18r1 during Th1 and Th2 differentiation 1

    PubMed Central

    Yu, Qing; Chang, Hua-Chen; Ahyi, Ayele-Nati N.; Kaplan, Mark H.

    2008-01-01

    The IL-18Rα chain is expressed on Th1 but not Th2 cells. We have recently shown that Stat4 is an important component of programming the Il18r1 locus (encoding IL-18Rα) for maximal expression in Th1 cells. Il18r1 is reciprocally repressed during Th2 development. In this report we demonstrate that the establishment of DNase hypersensitivity patterns that are distinct among undifferentiated CD4 T cells, Th1 and Th2 cells. Stat6 is required for the repression of Il18r1 expression and in Stat6-deficient Th2 cultures, mRNA levels, histone acetylation and H3K4 methylation levels are intermediate between levels observed in Th1 and Th2 cells. Despite the repressive effects of IL-4 during Th2 differentiation, we observed only modest binding of Stat6 to the Il18r1 locus. In contrast, we observed robust GATA-3 binding to a central region of the locus where DNase hypersensitivity sites overlapped with conserved non-coding sequences in Il18r1 introns. Ectopic expression of GATA-3 in differentiated Th1 cells repressed Il18r1 mRNA and surface expression of IL-18Rα. These data provide further mechanistic insight into transcription factor dependent establishment of Th subset-specific patterns of gene expression. PMID:18714006

  13. 4th Annual Conference for African-American Researchers in the Mathematical Sciences (CAARMS4). Preliminary Program

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tapia, Richard

    1998-06-01

    In June, The Center for Research on Parallel Computation (CRPC), an NSF-funded Science and Technology Center, hosted the 4th Annual Conference for African-American Reserachers in the Mathematical Sciences (CAARMS4) at Rice University. The main goal of this conference was to highlight current work by African-American researchers and graduate students in mathematics. This conference strengthened the mathematical sciences by encouraging the increased participation of African-American and underrepresented groups into the field, facilitating working relationships between them and helping to cultivate their careers. In addition to the talks there was a graduate student poster session and tutorials on topics in mathematics andmore » computer science. These talks, presentations, and discussions brought a broader perspective to the critical issues involving minority participation in mathematics.« less

  14. Semiconducting cubic titanium nitride in the Th 3 P 4 structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhadram, Venkata S.; Liu, Hanyu; Xu, Enshi

    We report the discovery of a long-sought-after phase of titanium nitride with stoichiometry Ti 3 N 4 using diamond anvil cell experiments combined with in situ high-resolution x-ray diffraction and Raman spectroscopy techniques, supported by ab initio calculations. Ti 3 N 4 crystallizes in the cubic Th 3 P 4 structure [space group I ¯ 4 3 d (220)] from a mixture of TiN and N 2 above ≈ 75 GPa and ≈ 2400 K. The density ( ≈ 5.22 g/cc) and bulk modulus ( K 0 = 290 GPa) of cubic- Ti 3 N 4 ( c - Timore » 3 N 4 ) at 1 atm, estimated from the pressure-volume equation of state, are comparable to rocksalt TiN. Ab initio calculations based on the GW approximation and using hybrid functionals indicate that c - Ti 3 N 4 is a semiconductor with a direct band gap between 0.8 and 0.9 eV, which is larger than the previously predicted values. The c - Ti 3 N 4 phase is not recoverable to ambient pressure due to dynamic instabilities, but recovery of Ti 3 N 4 in the defect rocksalt (or related) structure may be feasible.« less

  15. Adsorptive features of polyacrylamide-apatite composite for Pb2+, UO(2)2+ and Th4+.

    PubMed

    Ulusoy, Ulvi; Akkaya, Recep

    2009-04-15

    Micro-composite of polyacrylamide (PAA) and apatite (Apt) was prepared by direct polymerization of acrylamide in a suspension of Apt and characterized by means of FT-IR, XRD, SEM and BET analysis. The adsorptive features of PAA-Apt and Apt were then investigated for Pb(2+), UO(2)(2+) and Th(4+) in view of dependency on ion concentration, temperature, kinetics, ion selectivity and reusability. Experimentally obtained isotherms were evaluated with reference to Langmuir, Freundlich and Dubinin-Radushkevich (DR) models. Apt in PAA-Apt had higher adsorption capacity (0.81, 1.27 and 0.69 mol kg(-1)) than bare Apt (0.28, 0.41 and 1.33 mol kg(-1)) for Pb(2+) and Th(4+), but not for UO(2)(2+). The affinity to PAA-Apt increased for Pb(2+) and UO(2)(2+) but not changed for Th(4+). The values of enthalpy and entropy changed were positive for all ions for both Apt and PAA-Apt. Free enthalpy change was DeltaG<0. Well compatibility of adsorption kinetics to the pseudo-second-order model predicated that the rate-controlling step was a chemical sorption. This was consistent with the free energy values derived from DR model. The reusability tests for Pb(2+) for five uses proved that the composite was reusable to provide a mean adsorption of 53.2+/-0.7% from 4x10(-3)M Pb(2+) solution and complete recovery of the adsorbed ion was possible (98+/-1%). The results of this investigation suggested that the use of Apt in the micro-composite form with PAA significantly enhanced the adsorptive features of Apt.

  16. CHANGES IN THE REGIONAL PREVALENCE OF CHILD OBESITY IN 4th, 8th, AND 11th GRADE STUDENTS IN TEXAS FROM 2000–2002 TO 2004–2005

    PubMed Central

    Kelder, S. H.; Pérez, A.; Day, R. S.; Benoit, J.; Frankowski, R. F.; Walker, J. L.; Lee, E. S.

    2016-01-01

    Although national and state estimates of child obesity are available, data at these levels are insufficient to monitor effects of local obesity prevention initiatives. The purpose of this study was to examine regional changes in the prevalence of obesity due to state-wide policies and programs among children in grades 4, 8, and 11 in Texas Health Service Regions (HSR) between 2000–2002 and 2004–2005, and nine selected counties in 2004–2005. A cross-sectional, probability-based sample of 23,190 Texas students in grades 4, 8, and 11 were weighed and measured to obtain body mass index (BMI). Obesity was greater than 95th percentile for BMI by age/sex using CDC growth charts. Child obesity prevalence significantly decreased between 2000–2002 and 2004–2005 for 4th grade students in the El Paso HSR (−7.0%, p=0.005). A leveling off in the prevalence of obesity was noted for all other regions for grades 4, 8 and 11. County-level data supported the statistically significant decreases noted in the El Paso region. The reduction of child obesity levels observed in the El Paso area is one of the few examples of effective programs and policies based on a population-wide survey: in this region, a local foundation funded extensive regional implementation of community programs for obesity prevention, including an evidence-based elementary school-based health promotion program, adult nutrition and physical activity programs, and a radio and television advertising campaign. Results emphasize the need for sustained school, community and policy efforts, and that these efforts can result in decreases in child obesity at the population level. PMID:19798066

  17. Association of Grade Configuration with School Climate for 7th and 8th Grade Students

    ERIC Educational Resources Information Center

    Malone, Marisa; Cornell, Dewey; Shukla, Kathan

    2017-01-01

    Educational authorities have questioned whether middle schools provide the best school climate for 7th and 8th grade students, and proposed that other grade configurations such as K-8th grade schools may provide a better learning environment. The purpose of this study was to compare 7th and 8th grade students' perceptions of 4 key features of…

  18. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease.

    PubMed

    Kidd, Parris

    2003-08-01

    One theory of immune regulation involves homeostasis between T-helper 1 (Th1) and T-helper 2 (Th2) activity. The Th1/Th2 hypothesis arose from 1986 research suggesting mouse T-helper cells expressed differing cytokine patterns. This hypothesis was adapted to human immunity, with Th1- and Th2-helper cells directing different immune response pathways. Th1 cells drive the type-1 pathway ("cellular immunity") to fight viruses and other intracellular pathogens, eliminate cancerous cells, and stimulate delayed-type hypersensitivity (DTH) skin reactions. Th2 cells drive the type-2 pathway ("humoral immunity") and up-regulate antibody production to fight extracellular organisms; type 2 dominance is credited with tolerance of xenografts and of the fetus during pregnancy. Overactivation of either pattern can cause disease, and either pathway can down-regulate the other. But the hypothesis has major inconsistencies; human cytokine activities rarely fall into exclusive pro-Th1 or -Th2 patterns. The non-helper regulatory T cells, or the antigen-presenting cells (APC), likely influence immunity in a manner comparable to Th1 and Th2 cells. Many diseases previously classified as Th1 or Th2 dominant fail to meet the set criteria. Experimentally, Th1 polarization is readily transformed to Th2 dominance through depletion of intracellular glutathione, and vice versa. Mercury depletes glutathione and polarizes toward Th2 dominance. Several nutrients and hormones measurably influence Th1/Th2 balance, including plant sterols/sterolins, melatonin, probiotics, progesterone, and the minerals selenium and zinc. The long-chain omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) significantly benefit diverse inflammatory and autoimmune conditions without any specific Th1/Th2 effect. Th1/Th2-based immunotherapies, e.g., T-cell receptor (TCR) peptides and interleukin-4 (IL-4) injections, have produced mixed results to date.

  19. Parents in Partnership for Proficiency: For 3rd & 4th Graders and Their Families.

    ERIC Educational Resources Information Center

    Neiner, Christine; And Others

    This document contains a series of learning materials for 3rd and 4th graders and their families. The materials are designed to augment classroom learning. Included are worksheets, games, and other skill building activities for writing, reading, math, citizenship, and science. These activities are meant to help children prepare for proficiency…

  20. Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of Brucella melitensis infection in mice.

    PubMed

    Vitry, Marie-Alice; De Trez, Carl; Goriely, Stanislas; Dumoutier, Laure; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

    2012-12-01

    Brucella spp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control of Brucella infection. The importance of lymphocyte subsets in the control of Brucella growth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control of Brucella melitensis 16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4(+) T cells in the control of B. melitensis infection, whereas IFN-γ-producing CD8(+) T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course of B. melitensis infection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis.

  1. New high-pressure polymorph of In{sub 2}S{sub 3} with defect Th{sub 3}P{sub 4}-type structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lai, Xiaojing; Zhu, Feng; Wu, Ye

    The high pressure behavior of β-In{sub 2}S{sub 3} (I4{sub 1}/amd and Z=16) has been studied by in situ synchrotron radiation X-ray diffraction combined with diamond anvil cell up to 71.7 GPa. Three pressure-induced phase transitions are evidenced at ∼6.6 GPa, ∼11.1 GPa at room temperature and 35.6 GPa after the high-temperature annealing using a portable laser heating system. The new polymorph of In{sub 2}S{sub 3} at 35.6 GPa is assigned to the denser cubic defect Th{sub 3}P{sub 4} structure (I4¯3d and Z=5.333), whose unit-cell parameters are a=7.557(1) Å and V=431.6(2) Å{sup 3}. The Th{sub 3}P{sub 4}-type phase can be stablemore » at least up to 71.7 GPa and cannot be preserved at ambient pressure. The pressure–volume relationship is well described by the second-order Birch–Murnaghan Equation of State, which yields B{sub 0}=63(3) GPa and B{sub 0}′=4 (fixed) for the β-In{sub 2}S{sub 3} phase and B{sub 0}=87(3) GPa and B{sub 0}′=4 (fixed) for the defect Th{sub 3}P{sub 4}-type phase respectively. - Graphical abstract: The structure and Rietveld refinement of new polymorph the defect Th{sub 3}P{sub 4}-type In{sub 2}S{sub 3}. This structure was observed at 35.6 GPa after laser heating by X-ray diffraction. Display Omitted - Highlights: Three pressure-induced phase transitions of β-In{sub 2}S{sub 3} were observed. β-In{sub 2}S{sub 3} was stable up to 6.6 GPa. The defect Th{sub 3}P{sub 4}-type In{sub 2}S{sub 3} was identified at 35.6 GPa after laser heating and was stable up to 71.7 GPa. Elastic properties of β-In{sub 2}S{sub 3} and Th{sub 3}P{sub 4}-type In{sub 2}S{sub 3} are well presented by Birch–Murnaghan EoS.« less

  2. Spiritual Health Scale 2011: Defining and Measuring 4th Dimension of Health

    PubMed Central

    Dhar, Neera; Chaturvedi, SK; Nandan, Deoki

    2011-01-01

    In the midst of physical comforts provided by the unprecedented developments in all spheres of life, the humanity is at cross roads and looking at something beyond these means. Spirituality has now been identified globally as an important aspect for providing answers to many questions related to health and happiness. The World Health Organization is also keen at looking beyond physical, mental and social dimensions of the health, and the member countries are actively exploring the 4th Dimension of the health i.e. the spiritual health and its impact on the overall health and happiness of an individual. National Institute of Health and Family Welfare (NIHFW), realized this need and initiated a research study in this direction. In this study, an effort was made to define this 4th Dimension of health from a common worldly person's perspective and measure it. 3 Domains, 6 Constructs and 27 Determinants of spiritual health were identified through a scientific process. A statistically reliable and valid Spiritual Health Scale (SHS 2011) containing 114 items has been developed. Construct validity and test- retest reliability has been established for urban educated adult population. The scale is first of its kind in the world to measure the spiritual health of a common worldly person, which is devoid of religious and cultural bias. Its items have universal applicability. PMID:22279257

  3. Reliability of a new 4th generation FloTrac algorithm to track cardiac output changes in patients receiving phenylephrine.

    PubMed

    Ji, Fuhai; Li, Jian; Fleming, Neal; Rose, David; Liu, Hong

    2015-08-01

    Phenylephrine is often used to treat intra-operative hypotension. Previous studies have shown that the FloTrac cardiac monitor may overestimate cardiac output (CO) changes following phenylephrine administration. A new algorithm (4th generation) has been developed to improve performance in this setting. We performed a prospective observational study to assess the effects of phenylephrine administration on CO values measured by the 3rd and 4th generation FloTrac algorithms. 54 patients were enrolled in this study. We used the Nexfin, a pulse contour method shown to be insensitive to vasopressor administration, as the reference method. Radial arterial pressures were recorded continuously in patients undergoing surgery. Phenylephrine administration times were documented. Arterial pressure recordings were subsequently analyzed offline using three different pulse contour analysis algorithms: FloTrac 3rd generation (G3), FloTrac 4th generation (G4), and Nexfin (nf). One minute of hemodynamic measurements was analyzed immediately before phenylephrine administration and then repeated when the mean arterial pressure peaked. A total of 157 (4.6 ± 3.2 per patient, range 1-15) paired sets of hemodynamic recordings were analyzed. Phenylephrine induced a significant increase in stroke volume (SV) and CO with the FloTrac G3, but not with FloTrac G4 or Nexfin algorithms. Agreement between FloTrac G3 and Nexfin was: 0.23 ± 1.19 l/min and concordance was 51.1%. In contrast, agreement between FloTrac G4 and Nexfin was: 0.19 ± 0.86 l/min and concordance was 87.2%. In conclusion, the pulse contour method of measuring CO, as implemented in FloTrac 4th generation algorithm, has significantly improved its ability to track the changes in CO induced by phenylephrine.

  4. Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy.

    PubMed

    Simonovic, Snezana Zivancevic; Mihaljevic, Olgica; Majstorovic, Ivana; Djurdjevic, Predrag; Kostic, Irena; Djordjevic, Olivera Milosevic; Teodorovic, Ljiljana Mijatovic

    2015-01-01

    Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. The aim of this study was to evaluate cytokine profiles in patients with differentiated thyroid cancer (DTC) before and 7 days after radioactive iodine (131-I) therapy. Cytokine levels were determined in supernatants obtained from phytohemagglutinin-stimulated whole blood cultures of 13 patients with DTC and 13 control subjects. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ), interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13) and interleukin 10 (IL-10); Th9-interleukin-9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for Human Th1/Th2/Th9/Th17/Th22. We have shown that peripheral blood cells of DTC patients produce significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. The 131-I therapy led to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Despite this, the calculated cytokine ratios (Th1/Th2) in DTC patients before and 7 days after 131-I therapy were not different from those in healthy subjects. DTC patients have significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. There is no influence of hypothyroidism or stage of disease on cytokine production in DTC patients before 131-I therapy. The radioactive 131-I therapy leads to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Additional studies are needed to determine the significance of these findings.

  5. Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.

    PubMed

    Czarnowicki, Tali; Esaki, Hitokazu; Gonzalez, Juana; Malajian, Dana; Shemer, Avner; Noda, Shinji; Talasila, Sreya; Berry, Adam; Gray, Jayla; Becker, Lauren; Estrada, Yeriel; Xu, Hui; Zheng, Xiuzhong; Suárez-Fariñas, Mayte; Krueger, James G; Paller, Amy S; Guttman-Yassky, Emma

    2015-10-01

    Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01). These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections

  6. The ThPOK transcription factor differentially affects the development and function of self-specific CD8(+) T cells and regulatory CD4(+) T cells.

    PubMed

    Twu, Yuh-Ching; Teh, Hung-Sia

    2014-03-01

    The zinc finger transcription factor ThPOK plays a crucial role in CD4 T-cell development and CD4/CD8 lineage decision. In ThPOK-deficient mice, developing T cells expressing MHC class II-restricted T-cell receptors are redirected into the CD8 T-cell lineage. In this study, we investigated whether the ThPOK transgene affected the development and function of two additional types of T cells, namely self-specific CD8 T cells and CD4(+) FoxP3(+) T regulatory cells. Self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11 and proliferation in response to either IL-2 or IL-15. The ThPOK transgene converted these self-specific CD8 T cells into CD4 T cells. The converted CD4(+) T cells are no longer self-reactive, lose the characteristics of self-specific CD8 T cells, acquire the properties of conventional CD4 T cells and survive poorly in peripheral lymphoid organs. By contrast, the ThPOK transgene promoted the development of CD4(+) FoxP3(+) regulatory T cells resulting in an increased recovery of CD4(+) FoxP3(+) regulatory T cells that expressed higher transforming growth factor-β-dependent suppressor activity. These studies indicate that the ThPOK transcription factor differentially affects the development and function of self-specific CD8 T cells and CD4(+) FoxP3(+) regulatory T cells. © 2013 John Wiley & Sons Ltd.

  7. Direct Measurement of Initial 230TH/ 232TH Ratios in Central Texas Speleothems for More Accurate Age Determination

    NASA Astrophysics Data System (ADS)

    Wortham, B. E.; Banner, J. L.; James, E.; Loewy, S. L.

    2013-12-01

    , 14.6 × 0.83 ppm, 5.8 × 0.56 ppm, and 5.9 × 0.60 ppm, which are higher and more precise than the value commonly assumed for initial 230Th/232Th, 4.4 × 4.4 ppm. Soil sampled above Westcave, a potential source of detrital Th incorporated into speleothems, also has a high calculated 230Th/232Th. We calculate soil 230Th/232Th from measured U and Th concentrations of soil leachates (using DI water and ammonium acetate). Calculated 230Th/232Th for Westcave soils range from 0.39 to 28.4 ppm, which encompasses the range of initial 230Th/232Th values found in the modern calcite. Soil leachates from Natural Bridge Caverns and Inner Space Cavern were analyzed by the same method, yielding calculated 230Th/232Th ranging from 1.5 to 12.6 ppm (Natural Bridge), and from 1.43 to 272 ppm (Inner Space). Soil and calcite data indicate that the commonly assumed initial 230Th/232Th is not always applicable and that initial 230Th/232Th can be estimated more accurately by measuring Th isotope ratios in modern calcite and soils to determine speleothem U-series ages.

  8. Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma.

    PubMed

    Koh, Byung Hee; Hwang, Soo Seok; Kim, Joo Young; Lee, Wonyong; Kang, Min-Jong; Lee, Chun Geun; Park, Jung-Won; Flavell, Richard A; Lee, Gap Ryol

    2010-06-08

    Previous studies have shown that Th2 cytokine genes on mouse chromosome 11 are coordinately regulated by the Th2 locus control region (LCR). To examine the in vivo function of Th2 LCR, we generated CD4-specific Th2 LCR-deficient (cLCR KO) mice using Cre-LoxP recombination. The number of CD4 T cells in the cLCR KO mouse was comparable to that in wild-type mice. The expression of Th2 cytokines was dramatically reduced in in vitro-stimulated naïve CD4 T cells. Deletion of the LCR led to a loss of general histone H3 acetylation and histone H3-K4 methylation, and demethylation of DNA in the Th2 cytokine locus. Upon ovalbumin challenge in the mouse model of allergic asthma, cLCR KO mice exhibited marked reduction in the recruitment of eosinophils and lymphocytes in the bronchoalveolar lavage fluid, serum IgE level, lung airway inflammation, mucus production in the airway walls, and airway hyperresponsiveness. These results directly demonstrate that the Th2 LCR is critically important in the regulation of Th2 cytokine genes, in chromatin remodeling of the Th2 cytokine locus, and in the pathogenesis of allergic asthma.

  9. (232)Th(d,4n)(230)Pa cross-section measurements at ARRONAX facility for the production of (230)U.

    PubMed

    Duchemin, C; Guertin, A; Haddad, F; Michel, N; Métivier, V

    2014-05-01

    (226)Th (T1/2=31 min) is a promising therapeutic radionuclide since results, published in 2009, showed that it induces leukemia cells death and activates apoptosis pathways with higher efficiencies than (213)Bi. (226)Th can be obtained via the (230)U α decay. This study focuses on the (230)U production using the (232)Th(d,4n)(230)Pa(β-)(230)U reaction. Experimental cross sections for deuteron-induced reactions on (232)Th were measured from 30 down to 19 MeV using the stacked-foil technique with beams provided by the ARRONAX cyclotron. After irradiation, all foils (targets as well as monitors) were measured using a high-purity germanium detector. Our new (230)Pa cross-section values, as well as those of (232)Pa and (233)Pa contaminants created during the irradiation, were compared with previous measurements and with results given by the TALYS code. Experimentally, same trends were observed with slight differences in orders of magnitude mainly due to the nuclear data change. Improvements are ongoing about the TALYS code to better reproduce the data for deuteron-induced reactions on (232)Th. Using our cross-section data points from the (232)Th(d,4n)(230)Pa reaction, we have calculated the thick-target yield of (230)U, in Bq/μA·h. This value allows now to a full comparison between the different production routes, showing that the proton routes must be preferred. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. High-pressure synthesis and characterization of new actinide borates, AnB4O8 (An=Th, U).

    PubMed

    Hinteregger, Ernst; Hofer, Thomas S; Heymann, Gunter; Perfler, Lukas; Kraus, Florian; Huppertz, Hubert

    2013-11-18

    New actinide borates ThB4O8 and UB4O8 were synthesized under high-pressure, high-temperature conditions (5.5 GPa/1100 °C for thorium borate, 10.5 GPa/1100 °C for the isotypic uranium borate) in a Walker-type multianvil apparatus from their corresponding actinide oxide and boron oxide. The crystal structure was determined on basis of single-crystal X-ray diffraction data that were collected at room temperature. Both compounds crystallized in the monoclinic space group C2/c (Z=4). Lattice parameters for ThB4O8: a=1611.3(3), b=419.86(8), c=730.6(2) pm; β=114.70(3)°; V=449.0(2) Å(3); R1=0.0255, wR2=0.0653 (all data). Lattice parameters for UB4O8: a=1589.7(3), b=422.14(8), c=723.4(2) pm; β=114.13(3)°; V=443.1(2) Å(3); R1=0.0227, wR2=0.0372 (all data). The new AnB4O8 (An=Th, U) structure type is constructed from corner-sharing BO4 tetrahedra, which form layers in the bc plane. One of the four independent oxygen atoms is threefold-coordinated. The actinide cations are located between the boron-oxygen layers. In addition to Raman spectroscopic investigations, DFT calculations were performed to support the assignment of the vibrational bands. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This isan open access article under the terms of the Creative Commons AttributionLicense, which permits use, distribution and reproduction in any medium,provided the original work is properly cited.

  11. Role of T-bet, the master regulator of Th1 cells, in the cytotoxicity of murine CD4+ T cells.

    PubMed

    Eshima, Koji; Misawa, Kana; Ohashi, Chihiro; Iwabuchi, Kazuya

    2018-05-01

    Although CD4 + T cells are generally regarded as helper T cells, some activated CD4 + T cells have cytotoxic properties. Given that CD4 + cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4 + T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to expression of IFN-γ has been well-documented, it remains unclear whether T-bet is involved in CD4 + T cell-mediated cytotoxicity. In this study, to investigate the ability of T-bet to confer cytolytic activity on CD4 + T cells, the T-bet gene (Tbx21) was introduced into non-cytocidal CD4 + T cell lines and their cytolytic function analyzed. Up-regulation of FasL (CD178), which provided the transfectant with cytotoxicity, was observed in Tbx21transfected CD4 + T cells but not in untransfected parental cells. In one cell line, T-bet transduction also induced perforin gene (Prf1) expression and Tbx21 transfectants efficiently killed Fas - target cells. Although T-bet was found to repress up-regulation of CD40L (CD154), which controls FasL-mediated cytolysis, the extent of CD40L up-regulation on in vitro-differentiated Th1 cells was similar to that on Th2 cells, suggesting the existence of a compensatory mechanism. These results collectively indicate that T-bet may be involved in the expression of genes, such as FasL and Prf1, which confer cytotoxicity on Th1 cells. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  12. Special Issue: 4th International Workshop on Space Radiation (IWSRR)

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    This special issue of the journal "Radiation and Environmental Biophysics" contains 20 peer-reviewed papers contributed by leading space radiation researcher's world-wide attending the 4th IWSRR. Manuscripts cover a broad range of topics ranging from radiation environments and transport in shielding and planetary surfaces to new results in understanding the biological effects of protons and high-charge and energy (HZE) nuclei on the risk of cancer, and degenerative diseases such as central nervous system effects, heart disease, and cataracts. The issue provides a snapshot of the state-of-the-art of the research in this field, demonstrating both the important results gathered in the past few years with experiments at accelerators, and the need for more research to quantify the risk and develop countermeasures.

  13. From palmistry to anthropometry: can 2nd to 4th digit length (2D:4D) predict the risk of prostate cancer?

    PubMed

    Salomão, Layla; Figueiredo, Rui Teófilo; Oliveira Santos, Rafael; Damião, Ronaldo; da Silva, Eloisio Alexsandro

    2014-01-01

    The 2nd to 4th digit length (2D:4D) is inversely related to androgen exposure during the fetal period, which may represent a risk factor for several steroid-related diseases. We aimed to evaluate the relationship between 2D:4D ratio and the risk of developing prostate cancer (PCa). We assessed the 2D:4D ratio of 474 men >40 years old, stratified into three groups: group 1 (n = 222) patients with PCa, group 2 (n = 82) subjects with high risk of PCa, and group 3 (n = 170) men with low risk of PCa. Subjects were submitted to a digital picture of the ventral surface of the right hand and 2nd and 4th fingers measurements were determined by the distance from the proximal crease to the tip using computer-assisted analysis. The mean serum prostate-specific antigen level was 7.5 ng/ml in the high-risk group and 0.92 ng/ml in the low-risk group (p < 0.05). The mean 2D:4D ratios were 0.96 ± 0.04, 0.97 ± 0.04 and 0.96 ± 0.04 for the PCa, high-risk and low-risk groups, respectively, and no difference was found among the three groups (p = 0.12). Anthropometry of the hand using the 2D:4D ratio is not a predictor of PCa. 2013 S. Karger AG, Basel.

  14. Nocardia rubra cell-wall skeleton promotes CD4+ T cell activation and drives Th1 immune response.

    PubMed

    Wang, Guangchuan; Wu, Jie; Miao, Miao; Dou, Heng; Nan, Ning; Shi, Mingsheng; Yu, Guang; Shan, Fengping

    2017-08-01

    Several lines of evidences have shown that Nocardia rubra cell wall skeleton (Nr-CWS) has immunoregulatory and anti-tumor activities. However, there is no information about the effect of Nr-CWS on CD4 + T cells. The aim of this study was to explore the effect of Nr-CWS on the phenotype and function of CD4 + T cells. Our results of in vitro experiments showed that Nr-CWS could significantly up-regulate the expression of CD69 and CD25 on CD4 + T cells, promote the proliferation of CD4 + T cells, increase the production of IFN-γ, TNF-α and IL-2 in the supernatants, but has no significant effect on the apoptosis and death of CD4 + T cells. Results of in vivo experiments showed that Nr-CWS could promote the proliferation of CD4 + T cells, and increase the production of IL-2, IFN-γ and TNF-α (Th1 type cytokines). These data suggest that Nr-CWS can enhance the activation of CD4 + T cells, promote the proliferation of CD4 + T cells and the differentiation of CD4 + T cells to Th1 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Best Practices for Improving the Writing of 3rd and 4th Grade Students

    ERIC Educational Resources Information Center

    Eftekhari, Parastou Afshar

    2017-01-01

    Scores on a state comprehensive assessment test showed that writing skills of 4th grade students enrolled in a K-8 magnet school in the southeastern part of the United States were below target. The assistant principal of the K-8 magnet school explained that a review of 3-year longitudinal data revealed that the number of students who met…

  16. Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4-one in mice: Implication of the Th1- and Th17-cell-mediated immune responses.

    PubMed

    Kim, Byung-Hak; Yoon, Bo Ruem; Kim, Eun Kyoung; Noh, Kum Hee; Kwon, Sun-Ho; Yi, Eun Hee; Lee, Hyun Gyu; Choi, Jung Sook; Kang, Seong Wook; Park, In-Chul; Lee, Won-Woo; Ye, Sang-Kyu

    2016-06-15

    Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro-inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17-cell subsets by inhibiting the expression and production of their lineage-specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and endothelial dysfunction in resistant hypertension.

    PubMed

    Magen, Eli; Feldman, Arie; Cohen, Ziona; Alon, Dora Ben; Minz, Evegeny; Chernyavsky, Alexey; Linov, Lina; Mishal, Joseph; Schlezinger, Menacham; Sthoeger, Zev

    2010-02-01

    A possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies. To compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH). Blood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning. RAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7 cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/- 88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/- 63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma transforming growth factor-beta1 levels were significantly higher in the RAH group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/- 0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls (10.1 +/- 1.1%; P < 0.001). RAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-beta1 levels.

  18. The 4th Armored Division in the Encirclement of Nancy.

    DTIC Science & Technology

    1986-04-01

    Germans to bar the way. The Germans sent two depleted but still dangerous mechanized infantry divi- sions, the 3d and 15th Panzergrenadier, from Italy...when the 3d Panzergrenadier Division handily repulsed a crossing of the Moselle mounted by the 80th Infantry Division on 5 September. Having been...deceived for long. At 0100 on 13 September, the 3d Panzergrenadier Division hit the Dieulouard bridgehead with a strong counterattack, causing the corps

  19. The 4th Armored Division in the Encirclement of Nancy

    DTIC Science & Technology

    1986-04-01

    for the Germans to bar the way. The Germans sent two depleted but still dangerous mechanized infantry divi- sions, the 3d and 15th Panzergrenadier...Wood’s mis- givings were borne out when the 3d Panzergrenadier Division handily repulsed a crossing of the Moselle mounted by the 86th Infantry...not deceived for long. At 0100 on 13 September, the 3d Panzergrenadier Division hit the Dieulouard bridgehead with a strong counterattack, causing

  20. A selected review of abstracts from the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology.

    PubMed

    Chamberlain, Marc C

    2014-03-01

    The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO), San Francisco, CA, USA, 21-24 November 2013 The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO) was the largest neuro-oncology meeting that meets once every 4 years and brings together clinicians and scientists from all parts of the world whose focus is on new brain cancer clinical trials and research primarily pertaining to gliomas. The WFNO 2013 meeting included 1 education day, 2.5 days of presentation, 13 sunrise sessions, one town hall meeting, one mini-symposium, 130 oral presentations and 900 abstracts. This short meeting review highlights select adult clinical abstracts presented at WFNO 2013 that will only in part encompass the contents of a large and multifaceted meeting.

  1. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells

    PubMed Central

    Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z.; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.; Rosenberg, Eric S.; Yu, Xu G.

    2017-01-01

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells. PMID:28628034

  2. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

    PubMed

    Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-06-30

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

  3. Kidney retransplantation from HLA-incompatible living donors: A single-center study of 3rd/4th transplants.

    PubMed

    Barnes, James C H; Goodyear, Stephen J; Imray, Caitlin E A; Lam, For Tai; Kashi, Habib S; Tan, Lam Chin; Higgins, Robert; Imray, Christopher H E

    2017-11-01

    The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least two kidney transplants with a focus on those with antibody incompatibility. We analyzed 66 patients who underwent renal transplantation at a single center between 2003 and 2011. Consecutive patients receiving their 3rd or 4th kidney were case-matched with an equal number of 1st and 2nd transplants. Twenty-two 3rd and 4th kidney transplants were matched with 22 first and 22 seconds transplants. Operative times and length of stay were equivalent between the subgroups. Surgical complication rates were similar in all groups (22.7% in 1st and 2nd transplants, and 27.2% in 3rd/4th transplants). There was no significant difference in patient or graft survival over 5 years. Graft function was similar between transplant groups at 1, 3, and 5 years. Third and fourth kidney transplants can be performed safely with similar outcomes to 1st and 2nd transplants. Kidney retransplantation from antibody-incompatible donors may be appropriate for highly sensitized patients. © 2017 The Authors Clinical Transplantation Published by John Wiley & Sons Ltd.

  4. Beliefs about the causes of obesity in a national sample of 4th year medical students.

    PubMed

    Phelan, Sean M; Burgess, Diana J; Burke, Sara E; Przedworski, Julia M; Dovidio, John F; Hardeman, Rachel; Morris, Megan; van Ryn, Michelle

    2015-11-01

    Physician knowledge of the complex contributors to obesity varies. We do not know whether today's medical students are graduating with deep understanding of the causes of obesity. Our objective was to assess beliefs about causes of obesity in a national sample of 4th year medical students. We randomly selected 2000 4th year students from a random sample of 50 U.S. medical schools and asked them to rate the importance of several factors as causes of obesity. Of those invited, 1244 (62%) responded. We conducted latent class analysis to identify groups with similar response patterns. Most students demonstrated knowledge that obesity has multiple contributors. Students fell into 1 of 4 classes: (1) more likely to endorse all contributors (28%), (2) more likely to endorse physiological contributors (27%), (3) more likely to endorse behavioral or social contributors (24%), and (4) unlikely to endorse contributors outside of overeating and physical activity (22%). Though students were generally aware of multiple causes, there were 4 distinct patterns of beliefs, with implications for patient care. Targeted interventions may help to improve depth of knowledge about the causes of obesity and lead to more effective care for obese patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. TH-E-17A-09: High Quality and Artifact-Free 4D Cone Beam CT and Its Application in Adaptive Treatment Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niu, K; Li, K; Smilowitz, J

    2014-06-15

    Purpose: To develop a high quality 4D cone beam CT (4DCBCT) method that is immune to patient/couch truncations and to investigate its application in adaptive replanning of lung XRT. Methods: In this study, IRB-approved human subject CBCT data was acquired using a Varian on-board imager with 1 minute rotation time. The acquired projection data was retrospectively sorted into 20 respiratory phase bins, from which 4DCBCT images with high SNR and high temporal resolution were generated using Prior Image Constrained Compressed Sensing (PICCS). Couch and patient truncations generate strong data inconsistency in the projection data and artifacts in the 4DCBCT image.more » They were addressed using an adaptive PICCS method. The artifact-free PICCS-4DCBCT images were used to generate adaptive treatment plans for the same patient at the 10th (day 21) and 30th (day 47) fractions. Dosimetric impacts with and without PICCS- 4DCBCT were evaluated by isodose distributions, DVHs, and other dosimetric factors. Results: The adaptive PICCS-4DCBCT method improves image quality by removing residue truncation artifacts; measured universal image quality increased 37%. The isodose lines and DVHs with PICCS-4DCBCT-based adaptive replanning were significantly more conformal to PTV than without replanning due to changes in patient anatomy caused by progress of the treatment. The mean dose to PTV at the 10th fraction was 63.1Gy with replanning and 64.2Gy without replanning, where the prescribed dose was 60Gy, in 2Gy × 30 fractions. The mean dose to PTV at the 30th fraction was 61.6Gy with replanning and 64.9Gy without replanning. Lung V20 was 37.1%, 41.9% and 43.3% for original plan, 10th fraction plan and 30th fraction plan; with re-planning, Lung V20 was 37.1%, 32%, 27.8%. Conclusion: 4DCBCT imaging using adaptive PICCS is able to generate high quality, artifact-free images that potentially can be used to create replanning for improving radiotherapy of the lung. K Niu, K Li, J Smilowitz

  6. Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

    PubMed

    Dinc, Gunes; Pennington, Jarrod M; Yolcu, Esma S; Lawrenz, Matthew B; Shirwan, Haval

    2014-09-03

    The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Analysis of Th1, Th17 and regulatory T cells in tuberculosis case contacts.

    PubMed

    García Jacobo, R E; Serrano, C J; Enciso Moreno, J A; Gaspar Ramírez, O; Trujillo Ochoa, J L; Uresti Rivera, E E; Portales Pérez, D P; González-Amaro, R; García Hernández, M H

    2014-01-01

    We have hypothesized that individuals infected with Mycobacteriumtuberculosis that exhibit different patterns of immune reactivity in serial interferon (IFN)-γ release assays (IGRA's) correspond to different status within the immune spectrum of latent tuberculosis (TB). Accordingly, we analyzed the possible association between the consistent results (negative or positive) in an IGRA test and relevant immune parameters, mainly the levels of Th1 and Th17 lymphocytes and T regulatory (Treg) cells in the peripheral blood of TB case contacts. We found that individuals with a persistently positive IGRA showed increased levels of Th1 and Th17 lymphocytes upon in vitro stimulation with MTB antigens. In addition, a significant increase in the proportion of CD4+CTLA-4+ and CD4+Foxp3+ cells was detected in assays with blood samples from these individuals. Our data support that different immune phenotypes can be identified into the spectrum of latent TB, by combining different parameters of immune reactivity against MTB. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Pooled nucleic acid testing increases the diagnostic yield of acute HIV infections in a high-risk population compared to 3rd and 4th generation HIV enzyme immunoassays.

    PubMed

    Krajden, Mel; Cook, Darrel; Mak, Annie; Chu, Ken; Chahil, Navdeep; Steinberg, Malcolm; Rekart, Michael; Gilbert, Mark

    2014-09-01

    We compared a 3rd generation (gen) and two 4th gen HIV enzyme immunoassays (EIA) to pooled nucleic acid testing (PNAT) for the identification of pre- and early seroconversion acute HIV infection (AHI). 9550 specimens from males >18 year from clinics attended by men who have sex with men were tested by Siemens ADVIA Centaur(®) HIV 1/O/2 (3rd gen) and HIV Combo (4th gen), as well as by Abbott ARCHITECT(®) HIV Ag/Ab Combo (4th gen). Third gen non-reactive specimens were also tested by Roche COBAS(®) Ampliprep/COBAS® TaqMan HIV-1 Test v.2 in pools of 24 samples. Sensitivity and specificity of the three EIAs for AHI detection were compared. 7348 persons contributed 9435 specimens and had no evidence of HIV infection, 79 (94 specimens) had established HIV infection, 6 (9 specimens) had pre-seroconversion AHI and 9 (12 specimens) had early seroconversion AHI. Pre-seroconversion AHI cases were not detected by 3rd gen EIA, whereas 2/6 (33.3%) were detected by Siemens 4th gen, 4/6 (66.7%) by Abbott 4th gen and 6/6 (100%) by PNAT. All three EIAs and PNAT detected all individuals with early seroconversion AHI. Overall sensitivity/specificity for the EIAs relative to WB or NAT resolved infection status was 93.6%/99.9% for Siemens 3rd gen, 95.7%/99.7% for Siemens 4th gen and 97.9%/99.2% for Abbott 4th gen. While both 4th gen EIAs demonstrated improved sensitivity for AHI compared to 3rd gen EIA, PNAT identified more AHI cases than either 4th gen assay. PNAT is likely to remain a useful strategy to identify AHI in high-risk populations. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Sitagliptin inhibit human lymphocytes proliferation and Th1/Th17 differentiation in vitro.

    PubMed

    Pinheiro, Marcelo Maia; Stoppa, Caroline Lais; Valduga, Claudete Justina; Okuyama, Cristina Eunice; Gorjão, Renata; Pereira, Regina Mara Silva; Diniz, Susana Nogueira

    2017-03-30

    Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin. The immune modulation mechanisms analyzed were: cell proliferation, by MTT assay; cytokine quantification by ELISA or cytometric bead array (CBA), Th1/Th2/Th17 phenotyping by flow cytometric analysis and CD26 gene expression by real time PCR. The results showed that sitagliptin treatment inhibited the proliferation of PBMC-PHA stimulated cells in a dose dependent manner and decreased CD26 expression by these cells, suggesting that sitagliptin may interfere in CD26 expression, dimerization and cell signaling. Sitagliptin treatment not only inhibited IL-10 (p<0.05) and IFN-gamma (p=0.07) cytokines, but also completely abolish IL-6 expression by PBMCs (p<0.001). On the other hand, IL-4 were secreted in culture supernatants from sitagliptin treated cells. A statistically significant increase (p<0.05) in the ratio of TGF-beta/proliferation index after sitagliptin treatment (2627.97±1351.65), when comparing to untreated cells (646.28±376.94), was also demonstrated, indicating higher TGF-beta1 production by viable cells in cultures. Sitagliptin treatment induced a significantly (p<0.05) decrease in IL-17 and IFN-gamma intracellular expression compared with PHA alone. Also, the percentage of T CD4 + IL-17 + , T CD4 + IFNgamma + and T CD4 + IL-4 + cells were

  10. Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling

    PubMed Central

    Boniface, Katia; Bak-Jensen, Kristian S.; Li, Ying; Blumenschein, Wendy M.; McGeachy, Mandy J.; McClanahan, Terrill K.; McKenzie, Brent S.; Kastelein, Robert A.; de Waal Malefyt, René

    2009-01-01

    Prostaglandins, particularly prostaglandin E2 (PGE2), play an important role during inflammation. This is exemplified by the clinical use of cyclooxygenase 2 inhibitors, which interfere with PGE2 synthesis, as effective antiinflammatory drugs. Here, we show that PGE2 directly promotes differentiation and proinflammatory functions of human and murine IL-17–producing T helper (Th17) cells. In human purified naive T cells, PGE2 acts via prostaglandin receptor EP2- and EP4-mediated signaling and cyclic AMP pathways to up-regulate IL-23 and IL-1 receptor expression. Furthermore, PGE2 synergizes with IL-1β and IL-23 to drive retinoic acid receptor–related orphan receptor (ROR)-γt, IL-17, IL-17F, CCL20, and CCR6 expression, which is consistent with the reported Th17 phenotype. While enhancing Th17 cytokine expression mainly through EP2, PGE2 differentially regulates interferon (IFN)-γ production and inhibits production of the antiinflammatory cytokine IL-10 in Th17 cells predominantly through EP4. Furthermore, PGE2 is required for IL-17 production in the presence of antigen-presenting cells. Hence, the combination of inflammatory cytokines and noncytokine immunomodulators, such as PGE2, during differentiation and activation determines the ultimate phenotype of Th17 cells. These findings, together with the altered IL-12/IL-23 balance induced by PGE2 in dendritic cells, further highlight the crucial role of the inflammatory microenvironment in Th17 cell development and regulation. PMID:19273625

  11. 4th Circuit: asymptomatic HIV is not a disability under ADA.

    PubMed

    1997-09-05

    The 4th U.S. Circuit Court of Appeals ruled that [name removed], who is HIV-positive, cannot continue with his lawsuit alleging that NationsBank of Maryland fired him because of his HIV status. The court decided that [name removed] did not make a case of discrimination against his employer because his work performance was substandard. Additionally, the court ruled that HIV infection in and of itself does not constitute a disability and therefore [name removed] is not protected by the Americans with Disabilities Act (ADA). The court ruled that [name removed] failed to prove that his asymptomatic HIV infection was an impairment or that it substantially limits a major life activity. When the ADA was enacted in 1990 it was presumed that anyone with HIV would be protected from discrimination and reports filed by both the House of Representatives and the Senate indicated that legislators felt that HIV infection constituted an impairment. This ruling made by the 4th Circuit seems to discount the legislation's intent. The court rejected [name removed]'s suggestion that the ability to procreate and engage in intimate sexual relations was a limitation of a major life activity. Dissenters argued that the opinion is not based on sound medical facts because HIV, even if it is asymptomatic, is an impairment. The dissent also contends that Mr. [Name removed] was not given fair and ample opportunity to prove that his HIV infection is disabling. The court was in sharp disagreement relative to [name removed]'s job performance. The court majority said that [name removed] failed to meet sales goals and engaged in unprofessional behavior. The dissent countered that [name removed]'s sales record exceeded that of another employee who was not terminated.

  12. Food-based Science Curriculum Increases 4th Graders Multidisciplinary Science Knowledge

    PubMed Central

    Hovland, Jana A.; Carraway-Stage, Virginia G.; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R.; Collins, Angelo; Duffrin, Melani W.

    2013-01-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students’ understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4th graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009–2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4th grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students’ multidisciplinary science knowledge related to food. PMID:25152539

  13. CD4+ T-cell clones obtained from cattle chronically infected with Fasciola hepatica and specific for adult worm antigen express both unrestricted and Th2 cytokine profiles.

    PubMed Central

    Brown, W C; Davis, W C; Dobbelaere, D A; Rice-Ficht, A C

    1994-01-01

    The well-established importance of helper T (Th)-cell subsets in immunity and immunoregulation of many experimental helminth infections prompted a detailed study of the cellular immune response against Fasciola hepatica in the natural bovine host. T-cell lines established from two cattle infected with F. hepatica were characterized for the expression of T-cell surface markers and proliferative responses against F. hepatica adult worm antigen. Parasite-specific T-cell lines contained a mixture of CD4+, CD8+, and gamma/delta T-cell-receptor-bearing T cells. However, cell lines containing either fewer than 10% CD8+ T cells or depleted of gamma/delta T cells proliferated vigorously against F. hepatica antigen, indicating that these T-cell subsets are not required for proliferative responses in vitro. Seventeen F. hepatica-specific CD4+ Th-cell clones were examined for cytokine expression following concanavalin A stimulation. Biological assays to measure interleukin-2 (IL-2) or IL-4, gamma interferon (IFN-gamma), and tumor necrosis factor and Northern (RNA) blot analysis to verify the expression of IL-2, IL-4, and IFN-gamma revealed that the Th-cell clones expressed a spectrum of cytokine profiles. Several Th-cell clones were identified as Th2 cells by the strong expression of IL-4 but little or no IL-2 or IFN-gamma mRNA. The majority of Th-cell clones were classified as Th0 cells by the expression of either all three cytokines or combinations of IL-2 and IL-4 or IL-4 and IFN-gamma. No Th1-cell clones were obtained. All of the Th-cell clones expressed a typical memory cell surface phenotype, characterized as CD45Rlow, and all expressed the lymph node homing receptor (L selectin). These results are the first to describe cytokine responses of F. hepatica-specific T cells obtained from infected cattle and extend our previous analysis of Th0 and Th1 cells from cattle immune to Babesia bovis (W. C. Brown, V. M. Woods, D. A. E. Dobbelaere, and K. S. Logan, Infect. Immun. 61

  14. Spatial and Temporal Distribution of Initial 230TH/232TH in Sumatran Corals and its Influence on the Accurate Dating of Young Corals

    NASA Astrophysics Data System (ADS)

    Chiang, H.; Shen, C.; Meltzner, A. J.; Philibosian, B.; WU, C.; Sieh, K. E.; Wang, X.

    2012-12-01

    Accurate and precise determination of initial 230Th/232Th (230Th/232Th0) is important in dating young fossil corals, and it can significantly influence our understanding of paleoclimate, paleoceanographic and paleoseismic histories. A total of 47 unpublished and published isochrons (Shen et al., 2008; Meltzner et al., 2010, 2012; Philibosian et al., 2012), covering most of the Sumatran outer-arc islands, provide a more robust estimate of the 230Th/232Th0 variability in the region. The weighted average of 230Th/232Th0 atomic values is 4.7 (+5.5/-4.7) × 10-6 (2σ), consistent with the previously reported value of 6.5 ± 6.5 × 10-6 obtained from a handful of samples from the southern part of Sumatran outer-arc. Specifically, the calculated 230Th/232Th0 in the north and south are identical. The weighted mean of 3.5 (+7.0/-3.5) × 10-6 for fossil corals of 300-2000-yr old is slightly lower than the value of 5.4 ± 4.5 × 10-6 obtained from corals younger than 300 yrs B.P.. For corals containing less than 2 ppb of thorium, however, the age offset will be less than 10 yr by using different 230Th/232Th0, which is acceptable for most studies. We hereby recommend an updated 230Th/232Th0 value of 4.7 (+5.5/-4.7) × 10-6 for corals throughout the Sumatran outer-arc islands. For very high-precision age determination (<10 yr), coral samples with low Th concentration (< 2 ppb) are preferred.; ;

  15. PREFACE: 4th International Symposium on Instrumentation Science and Technology (ISIST'2006)

    NASA Astrophysics Data System (ADS)

    Jiubin, Tan

    2006-10-01

    On behalf of the International Program Committee of ISIST'2006 and the symposium coordinators, I would like to thank all the participants for their presence at the 4th International Symposium on Instrumentation Science and Technology (ISIST'2006), a platform for scientists, researchers and experts from different parts of the world to present their achievements and to exchange their views on ways and means to further develop modern instrumentation science and technology. In the present information age, instrumentation science and technology is playing a more and more important role, not only in the acquisition and conversion of information at the very beginning of the information transformation chain, but also in the transfer, manipulation and utilization of information. It provides an analysis and test means for bioengineering, medical engineering, life science, environmental engineering and micro/nanometer technology, and integrates these disciplines to form new subdivisions of their own. The major subject of the symposium is crossover and fusion between instrumentation science and technology and other sciences and technologies. ISIST'2006 received more than 800 full papers from 12 countries and regions, from which 300 papers were finally selected by the international program committee for inclusion in the proceedings of ISIST'2006, published in 2 volumes. The major topics include instrumentation basic theory and methodology, sensors and conversion technology, signal and image processing, instruments and systems, laser and optical fiber instrumentation, advanced optical instrumentation, optoelectronics instrumentation, MEMS, nanotechnology and instrumentation, biomedical and environmental instrumentation, automatic test and control. The International Symposium on Instrumentation Science and Technology (ISIST) is sponsored by ICMI, NSFC, CSM, and CIS, and organized by ICMI, HIT and IC-CSM, and held every two years. The 1st symposium was held in LuoYang, China in

  16. Design of a Nb3Sn Magnet for a 4th Generation ECR Ion Source

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prestemon, S,; Trillaud, F.; Caspi, S.

    2008-08-17

    The next generation of Electron Cyclotron Resonant (ECR) ion sources are expected to operate at a heating radio frequency greater than 40 GHz. The existing 3rd generation systems, exemplified by the state of the art system VENUS, operate in the 10-28 GHz range, and use NbTi superconductors for the confinement coils. The magnetic field needed to confine the plasma scales with the rf frequency, resulting in peak fields on the magnets of the 4th generation system in excess of 10 T. High field superconductors such as Nb{sub 3}Sn must therefore be considered. The magnetic design of a 4th. generation ECRmore » ion source operating at an rf frequency of 56 GHz is considered. The analysis considers both internal and external sextupole configurations, assuming commercially available Nb{sub 3}Sn material properties. Preliminary structural design issues are discussed based on the forces and margins associated with the coils in the different configurations, leading to quantitative data for the determination of a final magnet design.« less

  17. Computational aspects of the nonlinear normal mode initialization of the GLAS 4th order GCM

    NASA Technical Reports Server (NTRS)

    Navon, I. M.; Bloom, S. C.; Takacs, L.

    1984-01-01

    Using the normal modes of the GLAS 4th Order Model, a Machenhauer nonlinear normal mode initialization (NLNMI) was carried out for the external vertical mode using the GLAS 4th Order shallow water equations model for an equivalent depth corresponding to that associated with the external vertical mode. A simple procedure was devised which was directed at identifying computational modes by following the rate of increase of BAL sub M, the partial (with respect to the zonal wavenumber m) sum of squares of the time change of the normal mode coefficients (for fixed vertical mode index) varying over the latitude index L of symmetric or antisymmetric gravity waves. A working algorithm is presented which speeds up the convergence of the iterative Machenhauer NLNMI. A 24 h integration using the NLNMI state was carried out using both Matsuno and leap-frog time-integration schemes; these runs were then compared to a 24 h integration starting from a non-initialized state. The maximal impact of the nonlinear normal mode initialization was found to occur 6-10 hours after the initial time.

  18. Anti-IL-23 receptor monoclonal antibody prevents CD4+ T cell-mediated colitis in association with decreased systemic Th1 and Th17 responses.

    PubMed

    Imamura, Emiko; Taguchi, Katsunari; Sasaki-Iwaoka, Haruna; Kubo, Satoshi; Furukawa, Shigetada; Morokata, Tatsuaki

    2018-04-05

    Experimental colitis studies, including T cell-mediated colitis, indicate that IL-23 rather than IL-12 orchestrates intestinal inflammation in inflammatory bowel disease (IBD). Previous studies have identified the roles of IL-12 and IL-23 using mice deficient for their specific subunits, p35 and p19, respectively. However, these studies do not completely reflect the difference in roles between IL-12 and IL-23, especially since the discovery of novel IL-12 family cytokines, which also include p35 or p19 subunits. Here, to clarify the contribution of IL-12 and IL-23 in T cell-mediated colitis, we compared the efficacy of a monoclonal antibody (mAb) to an IL-23-specific receptor subunit with that of an anti-IL-12/23p40 mAb in a naive CD4 + T cell transfer model of experimental colitis, which is associated with enhanced Th1 and Th17 responses. Both antibodies almost completely prevented the development of colitis and showed reduced associated histological changes, including mucosal hyperplasia, infiltration of inflammatory cells and loss of goblet cells. The anti-IL-23 receptor mAb inhibited not only the systemic Th17-response but also the Th1-response, both of which were up-regulated in this model. These results suggest that IL-23, but not IL-12, signaling is critical for the development of colitis. Blockade of IL-23 signaling is a promising therapeutic approach for IBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Two actinide-organic frameworks constructed by a tripodal flexible ligand: Occurrence of infinite ((UO{sub 2})O{sub 2}(OH){sub 3}){sub 4n} and hexanuclear (Th{sub 6}O{sub 4}(OH){sub 4}) motifs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liang, Lingling; Zhang, Ronglan; Zhao, Jianshe, E-mail: jszhao@nwu.edu.cn

    Two new actinide metal-organic frameworks were constructed by using a tripodal flexible ligand tris (2-carboxyethyl) isocyanurate (H{sub 3}tci) under hydrothermal condition. The combination of H{sub 3}tci and uranyl nitrate hexahydrate in aqueous solution leads to the isolation of [(UO{sub 2}){sub 2}(H{sub 2}O){sub 4}]{sub 0.5}(tci){sub 2}(UO{sub 2}){sub 4}(OH){sub 4}·18H{sub 2}O (1), which contains two distinct UO{sub 2}{sup 2+} coordination environments. Four uranyl cations, linked through μ{sub 3}-OH respectively, result in the edge-sharing ribbons. Then, the layer structure is constructed by U-O clusters linked through other eight-coordinated uranyl unions, giving rise to a porous structure in the space. Topological analysis reveals thatmore » complex 1 belongs to a (4, 8)-connected net with a schläfli symbol of (3{sup 4.}2{sup 6.}3){sub 2}(3{sup 4.}4{sup 6.}5{sup 6.}6{sup 8.}7{sup 3.}8). Th{sub 3}(tci){sub 2}O{sub 2}(OH){sub 2}(H{sub 2}O){sub 3}·12H{sub 2}O (2) generated by the reaction of H{sub 3}tci and thorium nitrate tetrahydrate, possesses nine-fold coodinated Th(IV) centers with a monocapped square antiprismatic geometry. The hexamers “Th{sub 6}O{sub 4}(OH){sub 4}” motifs are connected together by the carboxylate groups, showing a three-dimensional structures. Complex 2 takes on an 8-connected architecture and the point symbol is (4{sup 24.}6{sup 4}). - Graphical abstract: Two new 3D actinide metal-organic frameworks were constructed by using a tripodal flexible ligand tris (2-carboxyethyl) isocyanurate (H3tci) and their topological structures were displayed. The infinite ((UO{sub 2})O{sub 2}(OH){sub 3}){sub 4n} and hexanuclear (Th{sub 6}O{sub 4}(OH){sub 4}) motifs were found in the title actinides networks.« less

  20. PREFACE: 4th International Conference on Safe Production and Use of Nanomaterials (Nanosafe2014)

    NASA Astrophysics Data System (ADS)

    Tardif, F.; Damlencourt, J.-F.; Schuster, F.; Gaultier, V.

    2015-05-01

    This volume contains a collection of contributions presented at the 4th International Conference on Safe Production and Use of Nanomaterials (NANOSAFE 2014) held in Grenoble, France, from 18th to 20th November 2014. The issues of fast progress in the field of Nanosafety are up to the potential benefits that nanotechnology can bring to mankind. Making more efficient - more sustainable - easier to share mineral resources, increasing the yields of new energy technologies, enabling drugs that act selectively and locally are just few examples of the wide range of nanomaterial applications that currently benefit humanity. Nevertheless, the dynamic development of nanomaterials requires the adhesion from the general public who rightly demand major progresses in Nanosafety as a prerequisite. This is our exciting responsibility and challenge! Following the successful outcome of the three past international conferences on safe production and use of nanomaterials: Nanosafe 2008, 2010 and 2012, the organizing committee has the pleasure to welcoming you again to Minatec, Grenoble with some of the most famous specialists in the field. This year, two new topics have been added dealing with the "New Application of Nanomaterials" and "Nano-responsible Development" in addition to the usual issues addressed in previous Nanosafe conferences such as Expology, Detection and Characterization, Toxicology, Environmental Interactions, Nanomaterials Release, Life Cycle Analysis, Regulation and Standardization, Risk Management. The debates in 2012 proved highly successful so this formula has been kept in 2014 with 3 round tables: Nano-Responsible Development, Risks and Benefits for the Environment, Toxicology Progress. In this 4th edition, there were more than 330 registered participants from 28 different countries including 160 oral presentation covering the whole Nanosafety issues in 12 sessions, satellite workshops and round tables. This high number of participants makes this edition one of

  1. Multi-Dimensional Asymptotically Stable 4th Order Accurate Schemes for the Diffusion Equation

    NASA Technical Reports Server (NTRS)

    Abarbanel, Saul; Ditkowski, Adi

    1996-01-01

    An algorithm is presented which solves the multi-dimensional diffusion equation on co mplex shapes to 4th-order accuracy and is asymptotically stable in time. This bounded-error result is achieved by constructing, on a rectangular grid, a differentiation matrix whose symmetric part is negative definite. The differentiation matrix accounts for the Dirichlet boundary condition by imposing penalty like terms. Numerical examples in 2-D show that the method is effective even where standard schemes, stable by traditional definitions fail.

  2. General Chemistry Collection for Students, 6th Edition

    NASA Astrophysics Data System (ADS)

    2002-05-01

    System requirements are given in Tables 2a and b. Some programs have additional special requirements. Please see the individual program abstracts at JCE Online or the documentation included on the CD-ROM for more specific information.

    Table 2a. Hardware Required <th>Computer> <th>CPU> <th>RAM> <th>Drives> <th>Graphics> <th bgcolor="#e5e5e5">Mac OSth> <th bgcolor="#e5e5e5">Windowsth>
    Power Macintosh ≥ 64 MB CD-ROMHard Drive ≥ 256 colors;≥ 800x600
    Pentium ≥ 64 MB CD-ROMHard Drive SVGA;≥ 256 colors;≥ 800x600
    Table 2b. Software Required <th>Computer> <th>Operating Systemth> <th>Other(required by one or more programs)th> <th bgcolor="#e5e5e5">Mac OSth> <th bgcolor="#e5e5e5">Windowsth>
  3. 77 FR 56208 - Filing Dates for the Kentucky Special Election in the 4th Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... FEDERAL ELECTION COMMISSION [Notice 2012-06] Filing Dates for the Kentucky Special Election in the 4th Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Kentucky has scheduled a general election on November 6, 2012, to fill the U.S...

  4. Modulation of mycobacterial-specific Th1 and Th17 cells in latent tuberculosis by coincident hookworm infection

    PubMed Central

    George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumaran, Paramasivam Paul; Chandrasekaran, Vedachalam; Nutman, Thomas B.; Babu, Subash

    2013-01-01

    Hookworm infections and tuberculosis are co-endemic in many parts of the world. It has been suggested that infection with helminth parasites could suppress the predominant Th1 (IFN-γ-mediated) response needed to control Mycobacterium tuberculosis (Mtb) infection and enhance susceptibility to infection and/or disease. To determine the role of coincident hookworm infection on responses at steady state and on Mtb – specific immune responses in latent tuberculosis (TB), we examined the cellular responses in individuals with latent TB with or without concomitant hookworm infection. By analyzing the expression of Th1, Th2 and Th17 subsets of CD4+ T cells, we were able to demonstrate that the presence of coincident hookworm infection significantly diminished both spontaneously expressed and Mtb – specific mono – and dual – functional Th1 and Th17 cells. Hookworm infection, in contrast, was associated with expanded frequencies of mono – and dual – functional Th2 cells at both steady state and upon antigen – stimulation. This differential induction of CD4+ T cell subsets was abrogated upon mitogen stimulation. In addition, coincident hookworm infection was associated with increased adaptive T regulatory (aTreg) cells but not natural regulatory T cells (nTregs) in latent TB. Finally, the CD4+ T cell cytokine expression pattern was also associated with alterations in the systemic levels of Th1 and Th2 cytokines. Thus, coincident hookworm infection exerts a profound inhibitory effect on protective Th1 and Th17 responses in latent tuberculosis and may predispose toward the development of active tuberculosis in humans. PMID:23576678

  5. Curcumin attenuates the scurfy-induced immune disorder, a model of IPEX syndrome, with inhibiting Th1/Th2/Th17 responses in mice.

    PubMed

    Lee, Gihyun; Chung, Hwan-Suck; Lee, Kyeseok; Lee, Hyeonhoon; Kim, Minhwan; Bae, Hyunsu

    2017-09-15

    Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period. C57BL/6 mice were separated into scurfy or wild-type litter mate groups by genotyping, and each group subsequently was separated into 2 subgroups that were fed a 1% curcumin containing or normal diet from the last day of breast-feeding. After weaning, pups were fed either a 1% curcumin containing or normal diet until all scurfy mice die for survival data. To elucidate immune cell proportions in spleen and lymph nodes, cells were analyzed by flowcytometry. Cellular cytokine production was accessed to investigate the effects of curcumin in T cell differentiation in vitro. Scurfy mice fed a 1% curcumin diet survived 4.0-fold longer compared to scurfy (92.5 days) mice fed a normal diet (23 days). A curcumin diet decreased all of the Th1/Th2/Th17 cell populations and attenuated diverse symptoms such as splenomegaly in scurfy mice. In vitro experiments showed that curcumin treatment directly decreased the Th1/Th2/Th17 cytokine production of IFN-γ, IL-4, and IL-17A in CD4 + T cells. Curcumin diet attenuated the scurfy-induced immune disorder, a model of IPEX syndrome, by inhibiting Th1/Th2/Th17 responses in mice. These results have implications for improving clinical therapy for patients with IPEX and other T cell related autoimmune diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. The effect of garlic consumption on Th1/Th2 cytokines in phytohemagglutinin (PHA) activated rat spleen lymphocytes.

    PubMed

    Zamani, Alireza; Vahidinia, Aliasghar; Ghannad, Masoud Sabouri

    2009-04-01

    The balance and regulation of T helper 1 (Th1) and Th2-type cytokines are important in the effective immune response to different diseases. To clarify the effect of garlic (Allium sativum L.) consumption on the Th1/Th2 balance, the secretion of gamma interferon (IFN-gamma) and interleukin-4 (IL-4), as two prototypes of Th1/Th2 cytokines, were compared in serum and supernatant of in vitro phytohemagglutinin activated rat spleen lymphocytes. Thirty male rats were divided equally into two groups. The treatment group received garlic solution in water (600 mg/kg/4 mL) and controls received distilled water by gavage. After 1 month, serum and supernatant of PHA activated spleen lymphocytes were analysed for IFN-gamma and IL-4 by the enzyme-linked immunosorbent assay test and thymus and spleen weights were measured. The garlic treatment group showed significantly decreased production of IFN-gamma from 101.73 +/- 4.62 to 74.64 +/- 4.64 pg/mL and significantly increased IL-4 production from 26.75 +/- 3.35 to 83.92 +/- 6.56 pg/mL (p < 0.001) in the supernatant of PHA induced spleen lymphocytes. The serum level of these cytokines was undetectable. The mean weight of thymuses in the garlic fed animals was significantly reduced from 0.456 +/- 0.016 to 0.368 +/- 0.023 g compared with the control group (p < 0.005). There were no significant differences between the spleen weights in the two groups. In conclusion, oral garlic treatment may favor a Th2 or humoral immune response. (c) 2008 John Wiley & Sons, Ltd.

  7. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation.

    PubMed

    Hansen, G; Berry, G; DeKruyff, R H; Umetsu, D T

    1999-01-01

    Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.

  8. General Chemistry Collection for Students (CD-ROM), Abstract of Special Issue 16, 4th Edition

    NASA Astrophysics Data System (ADS)

    2000-07-01

    The General Chemistry Collection contains both new and previously published JCE Software programs that are intended for use by introductory-level chemistry students. These peer-reviewed programs for Macintosh and for Windows are available on a single CD-ROM for convenient distribution to and access by students, and the CD may be adopted for students to purchase as they would a textbook. General Chemistry Collection covers a broad range of topics providing students with interesting information, tutorials, and simulations that will be useful to them as they study chemistry for the first time. There are 22 programs included in the General Chemistry Collection 4th Edition. Their titles and the general chemistry topics they cover are listed in Table 1. Features in This Edition General Chemistry Collection, 4th edition includes:

    • Lessons for Introductory Chemistry and INQUAL-S, two new programs not previously published by JCE Software (abstracts appear below)
    • Writing Electron Dot Structures (1) and Viscosity Measurement: A Virtual Experiment for Windows (2), two programs published individually by JCE Software
    • Periodic Table Live! LE, a limited edition of Periodic Table Live!, 2nd Edition (3) (this replaces Chemistry Navigator (4) and Illustrated Periodic Table (5))
    • Many of the programs from previous editions (6)1
    Hardware and Software Requirements System requirements are given in Table 2. Some programs have additional requirements. See the individual program abstracts at JCE Online, or documentation included on the CD-ROM for more specific information. Licensing and Discounts for Adoptions The General Chemistry Collection is intended for use by individual students. Institutions and faculty members may adopt General Chemistry Collection 4th Edition as they would a textbook. We can arrange for CDs to be packaged with laboratory manuals or other course materials or to be sold for direct distribution to students through the campus

  9. Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

    PubMed Central

    Brown, Chrysothemis C.; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M.; Noelle, Randolph J.

    2015-01-01

    Summary CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. PMID:25769610

  10. The St. Jude Cancer Education for Children Program Pilot Study: Determining the Knowledge Acquisition and Retention of 4th-Grade Students.

    PubMed

    Ayers, Katherine; Villalobos, Aubrey Van Kirk; Li, Zhenghong; Krasin, Matthew

    2016-03-01

    In 2006, St. Jude Children's Research Hospital began developing a school-based outreach program known as the St. Jude Cancer Education for Children Program (SJCECP). The program aimed to teach children about cancer and healthy habits that can prevent the formation of cancers into adulthood. During the 2010-2011 academic years, we conducted a pilot evaluation of the SJCECP curriculum, with the primary objective of evaluating the impact of the intervention on knowledge acquisition and retention among 4th-grade students participating in the program. Seven local schools and 481 students from the Memphis area participated in the program evaluation. The results of this study show that 4th-grade students are able to acquire gains in knowledge related to cells, cancer, and healthy living after receiving the SJCECP intervention. We conclude that the program can be a useful tool for improving knowledge of cancer concepts at the 4th-grade level.

  11. Streptococcus pneumoniae fructose-1,6-bisphosphate aldolase, a protein vaccine candidate, elicits Th1/Th2/Th17-type cytokine responses in mice.

    PubMed

    Elhaik Goldman, Shirin; Dotan, Shahar; Talias, Amir; Lilo, Amit; Azriel, Shalhevet; Malka, Itay; Portnoi, Maxim; Ohayon, Ariel; Kafka, Daniel; Ellis, Ronald; Elkabets, Moshe; Porgador, Angel; Levin, Ditza; Azhari, Rosa; Swiatlo, Edwin; Ling, Eduard; Feldman, Galia; Tal, Michael; Dagan, Ron; Mizrachi Nebenzahl, Yaffa

    2016-04-01

    Streptococcus pneumoniae (S. pneumoniae) is a major pathogen worldwide. The currently available polysaccharide-based vaccines significantly reduce morbidity and mortality. However, the inherent disadvantages of the currently available polysaccharide-based vaccines have motivated the search for other bacterial immunogens capable of eliciting a protective immune response against S. pneumoniae. Fructose-1,6-bisphosphate aldolase (FBA) is a glycolytic enzyme, which was found to localize to the bacterial surface, where it functions as an adhesin. Previously, immunizing mice with recombinant FBA (rFBA) in the presence of alum elicited a protective immune response against a lethal challenge with S. pneumoniae. Thus, the aim of the present study was to determine the cytokine responses that are indicative of protective immunity following immunization with rFBA. The protective effects against pneumococcal challenge in mice immunized with rFBA with complete Freund's adjuvant (CFA) in the initial immunization and with incomplete Freund's adjuvant (IFA) in booster immunizations surpassed the protective effects observed following immunization with either rFBA + alum or pVACfba. CD4+ T-cells obtained from the rFBA/CFA/IFA/IFA-immunized mice co-cultured with rFBA-pulsed antigen-presenting cells (APCs), exhibited a significantly greater proliferative ability than CD4+ T-cells obtained from the adjuvant-immunized mice co-cultured with rFBA‑pulsed APCs. The levels of the Th1-type cytokines, interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α and IL-12, the Th2-type cytokines, IL-4, IL-5 and IL-10, and the Th17-type cytokine, IL-17A, significantly increased within 72 h of the initiation of co-culture with CD4+ T-cells obtained from the rFBA‑immunized mice, in comparison with the co-cultures with CD4+ T-cells obtained from the adjuvant-immunized mice. Immunizing mice with rFBA resulted in an IgG1/IgG2 ratio of 41, indicating a Th2 response with substantial Th1

  12. Mangiferin attenuates TH1/TH2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model.

    PubMed

    Guo, Hong-Wei; Yun, Chen-Xia; Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T; Zhang, Jian; Deng, Jia-Gang

    2014-01-01

    Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

  13. Mangiferin Attenuates Th1/Th2 Cytokine Imbalance in an Ovalbumin-Induced Asthmatic Mouse Model

    PubMed Central

    Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T.; Zhang, Jian; Deng, Jia-Gang

    2014-01-01

    Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway. PMID:24955743

  14. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors.

    PubMed

    Wright, John M; Vered, Marilena

    2017-03-01

    The 4th edition of the World Health Organization's Classification of Head and Neck Tumours was published in January of 2017. This article provides a summary of the changes to Chapter 4 Tumours of the oral cavity and mobile tongue and Chapter 8 Odontogenic and maxillofacial bone tumours. Odontogenic cysts which were eliminated from the 3rd 2005 edition were included in the 4th edition as well as other unique allied conditons of the jaws. Many new tumors published since 2005 have been included in the 2017 classification.

  15. In vitro generated Th17 cells support the expansion and phenotypic stability of CD4(+)Foxp3(+) regulatory T cells in vivo.

    PubMed

    Zhou, Qiong; Hu, Ya; Howard, O M Zack; Oppenheim, Joost J; Chen, Xin

    2014-01-01

    CD4(+) T cells stimulate immune responses through distinct patterns of cytokine produced by Th1, Th2 or Th17 cells, or inhibit immune responses through Foxp3-expressing regulatory T cells (Tregs). Paradoxically, effector T cells were recently shown to activate Tregs, however, it remains unclear which Th subset is responsible for this effect. In this study, we found that Th17 cells expressed the highest levels of TNF among in vitro generated Th subsets, and most potently promoted expansion and stabilized Foxp3 expression by Tregs when co-transferred into Rag1(-/-) mice. Both TNF and IL-2 produced by Th17 cells contributed to this effect. The stimulatory effect of Th17 cells on Tregs was largely abolished when co-transferred with TNFR2-deficient Tregs. Furthermore, Tregs deficient in TNFR2 also supported a much lower production of IL-17A and TNF expression by co-transferred Th17 cells. Thus, our data indicate that the TNF-TNFR2 pathway plays a crucial role in the reciprocal stimulatory effect of Th17 cells and Tregs. This bidirectional interaction should be taken into account when designing therapy targeting Th17 cells, Tregs, TNF and TNFR2. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Spatial variability of initial 230Th/ 232Th in modern Porites from the inshore region of the Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Clark, Tara R.; Zhao, Jian-xin; Feng, Yue-xing; Done, Terry J.; Jupiter, Stacy; Lough, Janice; Pandolfi, John M.

    2012-02-01

    The main limiting factor in obtaining precise and accurate uranium-series (U-series) ages of corals that lived during the last few hundred years is the ability to constrain and correct for initial thorium-230 ( 230Th 0), which is proportionally much higher in younger samples. This is becoming particularly important in palaeoecological research where accurate chronologies, based on the 230Th chronometer, are required to pinpoint changes in coral community structure and the timing of mortality events in recent time (e.g. since European settlement of northern Australia in the 1850s). In this study, thermal ionisation mass spectrometry (TIMS) U-series dating of 43 samples of known ages collected from living Porites spp. from the far northern, central and southern inshore regions of the Great Barrier Reef (GBR) was performed to spatially constrain initial 230Th/ 232Th ( 230Th/ 232Th 0) variability. In these living Porites corals, the majority of 230Th/ 232Th 0 values fell within error of the conservative bulk Earth 230Th/ 232Th atomic value of 4.3 ± 4.3 × 10 -6 (2 σ) generally assumed for 230Th 0 corrections where the primary source is terrestrially derived. However, the results of this study demonstrate that the accuracy of 230Th ages can be further improved by using locally determined 230Th/ 232Th 0 values for correction, supporting the conclusion made by Shen et al. (2008) for the Western Pacific. Despite samples being taken from regions adjacent to contrasting levels of land modification, no significant differences were found in 230Th/ 232Th 0 between regions exposed to varying levels of sediment during river runoff events. Overall, 39 of the total 43 230Th/ 232Th 0 atomic values measured in samples from inshore reefs across the entire region show a normal distribution ranging from 3.5 ± 1.1 to 8.1 ± 1.1 × 10 -6, with a weighted mean of 5.76 ± 0.34 × 10 -6 (2 σ, MSWD = 8.1). Considering the scatter of the data, the weighted mean value with a more

  17. [3rd and 4th generation estroprogestatives French controversy: What effect on women's behavior?].

    PubMed

    Torres, Luis; Frapard, Christian; Daumas, Aurélie; Guibert, Nicolas; Lagouanelle-Simeoni, Marie-Claude; Rakoto, Jean-Claude; Villani, Patrick; Sambuc, Roland

    2016-04-01

    The primary objective of this study was to determine the reasons given by women who have changed or suspended their contraceptive method in 2013. What influence had the 3rd and 4th generation estroprogestatives (EP) French controversy and advices from doctors? Did they notice any consequences of the controversy on their lifestyle? Did they feel an impact on their behavior to health professionals? A study was conducted on women of childbearing age. Data collection took place between November 4 and December 16, 2013. The included subjects were between 18 and 55 years old females. Subjects were surveyed through an anonymous self-administered questionnaire distributed through pharmacies. The protocol called for the construction of clusters of subjects by having heard about, or not, of the controversy. Patients reporting having heard about the controversy have formed the "exposed" group while the others have formed the "unexposed" group. We compared two parameters between these two groups: the rate of subjects who reported having modified or suspended their contraceptive method in 2013 on one hand, and the rate of subjects who reported having made a change in their contraceptive method without or against advices from a doctor on the other hand. The sample included 988 subjects. The average age was 34 years. The level of exposure to media debates was 86.5%. Of the respondents, 19.8% were under 3rd or 4th generation EP in 2012, thus directly involved in the discussions and affected by health recommendations. Of the patients, 38.5% reported having changed their contraception in 2013. In these women, when they confirmed having heard about the controversy, 40.1% of them claimed to have conducted this process without or against advices from a doctor. This number dropped to 18.2% for those who had not heard of it. Media coverage of the 3rd and 4th generation EP vascular risk was not mentioned more by patients who suspended all medical contraceptive method than it was by

  18. Cage Regional Energy Budgets from the GLAS 4TH Order Model

    NASA Technical Reports Server (NTRS)

    Herman, G. F.; Alexder, M. A.; Shubert, S. D.

    1984-01-01

    The status and future plans of a study to (1) assess the accuracy of regional energy balance calculations obtained from the 4th-order model, (2) determine the impact of satellite data on the calculations, and (3) determine their utility for ocean energy transport studies are discussed. An equation is presented which models the vertically-integrated, time and areally-averaged total energy content of a region of the atmosphere extending from the surface to the top of the atmosphere. All of the terms of the equation were evaluated using early versions of the GLAS FGGE IIIb analysis, and analysis with satellite data deleted. Results show that the budget is dominated by the surface fluxes, net radiation, and horizontal atmospoheric divergence.

  19. Expression of MIF and TNFA in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables.

    PubMed

    Bautista-Herrera, L A; De la Cruz-Mosso, U; Morales-Zambrano, R; Villanueva-Quintero, G D; Hernández-Bello, J; Ramírez-Dueñas, M G; Martínez-López, E; Brennan-Bourdon, L M; Baños-Hernández, C J; Muñoz-Valle, J F

    2018-05-01

    Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = - 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.

  20. MyTH4-FERM myosins have an ancient and conserved role in filopod formation

    PubMed Central

    Goodson, Holly V.; Arthur, Ashley L.; Luxton, G. W. Gant; Houdusse, Anne; Titus, Margaret A.

    2016-01-01

    The formation of filopodia in Metazoa and Amoebozoa requires the activity of myosin 10 (Myo10) in mammalian cells and of Dictyostelium unconventional myosin 7 (DdMyo7) in the social amoeba Dictyostelium. However, the exact roles of these MyTH4-FERM myosins (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in the initiation and elongation of filopodia are not well defined and may reflect conserved functions among phylogenetically diverse MF myosins. Phylogenetic analysis of MF myosin domains suggests that a single ancestral MF myosin existed with a structure similar to DdMyo7, which has two MF domains, and that subsequent duplications in the metazoan lineage produced its functional homolog Myo10. The essential functional features of the DdMyo7 myosin were identified using quantitative live-cell imaging to characterize the ability of various mutants to rescue filopod formation in myo7-null cells. The two MF domains were found to function redundantly in filopod formation with the C-terminal FERM domain regulating both the number of filopodia and their elongation velocity. DdMyo7 mutants consisting solely of the motor plus a single MyTH4 domain were found to be capable of rescuing the formation of filopodia, establishing the minimal elements necessary for the function of this myosin. Interestingly, a chimeric myosin with the Myo10 MF domain fused to the DdMyo7 motor also was capable of rescuing filopod formation in the myo7-null mutant, supporting fundamental functional conservation between these two distant myosins. Together, these findings reveal that MF myosins have an ancient and conserved role in filopod formation. PMID:27911821

    1. Differential Expression of Serum MicroRNAs Supports CD4+ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma

      PubMed Central

      Kraft, Matthias F.; Gerber, Vincent

      2017-01-01

      MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis. We identified 11 significantly differentially expressed miRNAs between case and control horses: eca-miR-128, eca-miR-744, eca-miR-197, eca-miR-103, eca-miR-107a, eca-miR-30d, eca-miR-140-3p, eca-miR-7, eca-miR-361-3p, eca-miR-148b-3p and eca-miR-215. Pathway enrichment using experimentally validated target genes of the human homologous miRNAs showed a significant enrichment in the regulation of epithelial-to-mesenchymal transition (key player in airway remodeling in asthma) and the phosphatidylinositol (3,4,5)-triphosphate (PIP3) signaling pathway (modulator of CD4+ T cell maturation and function). Downregulated miR-128 and miR-744 supports a Th2/Th17 type immune response in severe equine asthma. PMID:29231896

    2. Treatment-seeking behaviour and social status of women with pelvic organ prolapse, 4th-degree obstetric tears, and obstetric fistula in western Uganda.

      PubMed

      Krause, Hannah G; Natukunda, Harriet; Singasi, Isaac; Hicks, Sylvia S W; Goh, Judith T W

      2014-11-01

      This study looks at a trilogy of women's health issues including severe pelvic organ prolapse, unrepaired 4th degree obstetric tears and obstetric fistula, all of which can cause significant suffering in the lives of women and their families. Women undergoing surgery for severe pelvic organ prolapse, unrepaired 4th degree obstetric tears and obstetric fistulae, were interviewed to assess their perceptions of what caused their condition, subsequent impact on their social situation and sexual activity, and whether they had sought treatment previously. One hundred fifty women participated in the survey, including 69 undergoing surgery for genito-urinary fistula, 25 with faecal incontinence only (including 24 women with unrepaired 4th degree obstetric tears and 1 woman with an isolated rectovaginal fistula), and 56 women with severe pelvic organ prolapse. All groups of women were exposed to abandonment by their families with 42 % of women with genito-urinary fistula, 21 % with unrepaired 4th degree obstetric tear, and 25 % of women with severe pelvic organ prolapse rejected by their husbands. Most of the women had actively sought treatment for their condition with no success due to unavailability of treatment or misinformation. This study confirms the social stigma associated with obstetric fistula, however also highlights the social stigma faced by women suffering with severe pelvic organ prolapse and unrepaired 4th degree obstetric tears in western Uganda. There is an urgent need for education and training in obstetric management and pelvic organ prolapse management in such areas of limited resources.

    3. Differential expression of circulating Th1/ Th2/ Th17 cytokines in serum of Chlamydia trachomatis-infected women undergoing incomplete spontaneous abortion.

      PubMed

      Prasad, Priya; Singh, Namita; Das, Banashree; Raisuddin, Sheikh; Dudeja, Mridu; Rastogi, Sangita

      2017-09-01

      The study aimed to elucidate role of Th1/Th2/Th17 cytokines in the immunopathogenesis of spontaneous abortion in Chlamydia trachomatis (Ct)-positive first-trimester aborters. Endometrial curettage tissue and serum were collected from 145 aborters (spontaneous abortion (SA) group, n = 85; recurrent miscarriage (RM) group, n = 60) and 120 controls attending Department of Obstetrics & Gynecology at Safdarjung hospital, New Delhi (India). Polymerase chain reaction was used to detect Ct plasmid/MOMP, while commercial cytometric bead array kit was utilized to estimate circulating serum cytokines. 13.7% aborters were Ct-positive, however, none was found to be infected among controls. IFN-γ, TNF-α, IL-2, IL-6 and IL-17A cytokines were significantly increased in SA group/RM group (Ct-infected) versus controls. IL-4 showed no difference between groups, while IL-10 was significantly elevated in controls versus Ct-infected subjects in SA group/RM group. Furthermore, IFN-γ, TNF-α, IL-6, IL-17A cytokines were significantly elevated in Ct-positive RM group versus Chlamydia-infected SA group. However, IL-2, IL-4 and IL-10 cytokines showed no significant difference between Ct-positive SA group versus infected RM group. Positive correlation was found between few cytokines (TNF-α and IFN-γ/IL-17A; IL-17A and IFN-γ/IL-6) in Ct-positive aborters. Our study clearly established the role of Th1/Th2/Th17 cytokines in the pathogenesis of spontaneous abortion in Ct-infected subjects and found that Chlamydia-positive recurrent aborters had a predominant Th1/Th17 bias. Copyright © 2017 Elsevier Ltd. All rights reserved.

    4. The Universal House: Energy, Shelter & The California Indian. Activity Guide, 4th/5th Grade.

      ERIC Educational Resources Information Center

      California Energy Extension Service, Sacramento.

      This activity guide links energy awareness with resource management and traditional California Indian cultures for the 3rd-6th grade span. The materials combine cooperative, hands-on activities with background information and learning extensions. The interdisciplinary lessons are built upon themes, concepts, and learning processes outlined in…

    5. Expansion of Pathogen-Specific Mono- and Multifunctional Th1 and Th17 Cells in Multi-Focal Tuberculous Lymphadenitis

      PubMed Central

      Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Nair, Dina; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

      2013-01-01

      Background Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB). Methods To identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25). Results Elevated frequencies of CD4+ T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4+ T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline. Conclusions Multi-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity. PMID:23451159

    6. Cord-Blood-Derived Mesenchymal Stromal Cells Downmodulate CD4+ T-Cell Activation by Inducing IL-10-Producing Th1 Cells

      PubMed Central

      Selleri, Silvia; Dieng, Mame Massar; Nicoletti, Simon; Louis, Isabelle; Beausejour, Christian; Le Deist, Françoise

      2013-01-01

      The mechanisms by which mesenchymal stromal cells (MSCs) induce immunomodulation are still poorly understood. In the current work, we show by a combination of polymerase chain reaction (PCR) array, flow cytometry, and multiplex cytokine data analysis that during the inhibition of an alloantigen-driven CD4+ T-cell response, MSCs induce a fraction of CD4+ T-cells to coexpress interferon-γ (IFNγ) and interleukin-10 (IL-10). This CD4+ IFNγ+ IL-10+ cell population shares properties with recently described T-cells originating from switched Th1 cells that start producing IL-10 and acquire a regulatory function. Here we report that IL-10-producing Th1 cells accumulated with time during T-cell stimulation in the presence of MSCs. Moreover, MSCs caused stimulated T-cells to downregulate the IFNγ receptor (IFNγR) without affecting IL-10 receptor expression. Further, the inhibitory effect of MSCs could be reversed by an anti-IFNγR-blocking antibody, indicating that IFNγ is one of the major players in MSC-induced T-cell suppression. Stimulated (and, to a lesser extent, resting) CD4+ T-cells treated with MSCs were able to inhibit the proliferation of autologous CD4+ T-cells, demonstrating their acquired regulatory properties. Altogether, our results suggest that the generation of IL-10-producing Th1 cells is one of the mechanisms by which MSCs can downmodulate an immune response. PMID:23167734

    7. Identification and analytical characterization of four synthetic cathinone derivatives iso-4-BMC, β-TH-naphyrone, mexedrone, and 4-MDMC.

      PubMed

      Qian, Zhenhua; Jia, Wei; Li, Tao; Liu, Cuimei; Hua, Zhendong

      2017-02-01

      New psychoactive substances (NPS) have gained much popularity on the global market over the last number of years. The synthetic cathinone family is one of the most prominent groups and this paper reports on the analytical properties of four synthetic cathinone derivatives: (1) 1-(4-bromophenyl)-1-(methylamino)propan-2-one (iso-4-BMC or iso-brephedrone), (2) 2-(pyrrolidin-1-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pentan-1-one (β-TH-naphyrone), (3) 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone), and (4) 2-(dimethylamino)-1-(4-methylphenyl)propan-1-one (4-MDMC). These identifications were based on liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. To our knowledge, no chemical or pharmacological data about compounds 1-3 have appeared until now, making this the first report on these compounds. The Raman and GC-MS data of 4 have been reported, but this study added the LC-MS and NMR data for additional characterization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

    8. Regulatory T cells and TH1/TH2 cytokines as immunodiagnosis keys in systemic autoimmune diseases.

      PubMed

      Ursaciuc, Cornel; Surcel, Mihaela; Ciotaru, Dan; Dobre, Maria; Pirvu, Ioana Ruxandra; Munteanu, Adriana Narcisa; Alecu, Mihail; Huică, Radu

      2010-01-01

      We assessed Helper T-cell involvement and possibilities to quantify the cell-based immune response in systemic autoimmune diseases (SAID) in 14 systemic lupus erythematosus (SLE) and 7 rheumatoid arthritis (RA) patients. The goals of investigation were T-CD4+/T-CD8+ ratio, regulatory T cells (Treg) status and TH1/TH2 serum cytokine profiles (IFN-gamma and IL-2, respectively IL-4 and IL-6). SLE group proved significant decreased average Treg value as compared to RA group and controls and showed significant low Treg incidence (86% patients). The distribution of high T-CD4+/T-CD8+ ratio registered no significant distinction among LES and RA groups. SAID patients presented low serum IFN-gamma (86% RA, 60% SLE), high IL-2 (57% RA) and high IL-6 (53% LES), but no significant IL-4 modification. We conclude that Treg percentage remains the only cellular criterion for SAID immune evaluation. In the same time, different secretion mechanisms seem to be involved in SAID, i.e. TH2 in SLE and TH1 in RA.

    9. Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles

      PubMed Central

      Toda, Tsuguto; Yoshino, Shin

      2016-01-01

      Nanomaterials present in cosmetics and food additives are used for industrial applications. However, their safety profile is unclear. Amorphous silica nanoparticles (nSPs) are a widely used nanomaterial and have been shown to induce inflammatory cytokines following intratracheal administration in mice. The current study investigated the adjuvant effect of nSP30 (nSP with a diameter of 33 nm) on T helper (Th)1, Th2, and Th17 immune responses as well as immunoglobulin (Ig) levels in mice. BALB/c mice were intraperitoneally administered ovalbumin (OVA) with or without varying doses and varying sizes of nSPs. The adjuvant effect of nSPs was investigated by measuring OVA-specific IgG antibodies in sera, OVA-specific proliferative responses of splenocytes, and the production of Th1, Th2, and Th17 cytokines. Aluminum hydroxide was used as a positive adjuvant control. Anti-OVA IgG production, splenocyte proliferative responses, and secretion of IFN-γ, IL-2, IL-4, IL-5, and IL-17 were increased significantly in mice receiving a combined injection of nSP30 (30 or 300 µg) with OVA compared with OVA alone or a combined injection with nSP30 (3 µg). The responses were nSP30 dose-dependent. When different sized nSPs were used (with 30, 100, and 1000 nm diameters), the responses to OVA were enhanced and were size-dependent. The smaller sized nSP particles had a greater adjuvant effect. nSPs appear to exert a size-dependent adjuvant effect for Th1, Th2, and Th17 immune responses. Understanding the mechanisms of nSP adjuvanticity might lead to the development of novel vaccine adjuvants and therapies for allergic diseases caused by environmental factors. PMID:27343242

    10. HIV infection impairs Th1 and Th17 Mycobacterium tuberculosis-specific T cell responses

      PubMed Central

      Murray, Lyle W; Satti, Iman; Meyerowitz, Jodi; Jones, Matthew; Willberg, Christian B; Ussher, James E; Goedhals, Dominique; Hurst, Jacob; Phillips, Rodney E; McShane, Helen

      2018-01-01

      Background HIV-infected individuals have a higher risk of developing active tuberculosis than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (M.tb)-specific CD4+ and CD8+ T cell responses contributed to this increased risk. Methods M.tb-specific T cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa were evaluated. Using a whole-blood flow cytometry assay, we measured expression of IFNγ, TNFα, IL-2 and IL-17 in CD4+ and CD8+ T cells in response to M.tb antigens (PPD, ESAT-6/CFP-10 (EC) and DosR regulon-encoded α-crystallin (Rv2031c)). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T cell responses to PPD and Rv2031c than HIV-uninfected subjects. M.tb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+ M.tb-specific T cell responses is antigen-specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T cell subset may be key to TB susceptibility in HIV-infected individuals. PMID:29546381

    11. Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease.

      PubMed

      Smart, J M; Kemp, A S

      2002-05-01

      Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to

    12. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells

      PubMed Central

      Kiniwa, Yukiko; Li, Jiang; Wang, Mingjun; Sun, Chuang; Lee, Jeffrey E.; Wang, Rong-Fu; Wang, Helen Y.

      2015-01-01

      Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4+ T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4+ T cell-mediated immunotherapy in melanoma. PMID:25993655

    13. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.

      PubMed

      Kiniwa, Yukiko; Li, Jiang; Wang, Mingjun; Sun, Chuang; Lee, Jeffrey E; Wang, Rong-Fu; Wang, Helen Y

      2015-01-01

      Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+) T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+) T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+) T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+) Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+) T cell-mediated immunotherapy in melanoma.

    14. IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients.

      PubMed

      Heo, Yu-Jung; Joo, Young-Bin; Oh, Hye-Jwa; Park, Mi-Kyung; Heo, Yang-Mi; Cho, Mi-La; Kwok, Seung-Ki; Ju, Ji-Hyeon; Park, Kyung-Su; Cho, Seok Goo; Park, Sung-Hwan; Kim, Ho-Youn; Min, Jun-Ki

      2010-01-04

      Interleukin-17-producing CD4(+) T cells (Th17 cells) are the dominant pathogenic cellular component in autoimmune inflammatory diseases, including autoimmune arthritis. IL-10 promotes the generation of Foxp3(+) regulatory T cells via the IL-10 receptor signal. The objective of this study was to examine whether IL-10, which acts as an anti-inflammatory cytokine, has a suppressive effect on the activation of human Th17 cells. Expression of IL-17 and IL-10 was examined immunohistochemically in tissue obtained from rheumatoid arthritis patients. Human peripheral blood CD4(+) T cells were isolated and cultured under various stimulatory conditions. Th17 cells and regulatory T (Treg) cells were detected by flow cytometry. The gene expression of related cytokines and transcription factors were assessed by ELISA and RT-PCR. IL-17 was overexpressed in rheumatoid arthritis patients. IL-10 treatment significantly decreased the numbers of IL-17-producing and RORc-expressing cells among human CD4(+) T cells that had been activated in vitro by Th17-differentiating conditions in autoimmune arthritis patients. IL-10 induced Foxp3(+) regulatory T cells in the human CD4(+) T cell population. Our results demonstrate that IL-17 is overexpressed in autoimmune disease patients and that IL-10 suppresses IL-17 expression. IL-10 may be useful in the treatment of autoimmune diseases.

    15. The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma

      PubMed Central

      Gupta, Kanupriya; Ogendi, Brian M. O.; Bakshi, Rakesh K.; Kapil, Richa; Press, Christen G.; Sabbaj, Steffanie; Lee, Jeannette Y.

      2017-01-01

      ABSTRACT Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine. PMID:28100498

    16. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

      NASA Astrophysics Data System (ADS)

      Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

      2016-04-01

      Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered through classroom observations and interviews in four Turkish elementary schools. Focus group interviews with 47 students and individual interviews with 17 teachers and 10 parents were conducted. Participants identified a wide range of SIS, including TV, magazines, newspapers, internet, peers, teachers, families, science centers/museums, science exhibitions, textbooks, science books, and science camps. Students reported using various SIS in school-based and non-school contexts to satisfy their cognitive, affective, personal, and social integrative needs. SIS were used for science courses, homework/project assignments, examination/test preparations, and individual science-related research. Students assessed SIS in terms of the perceived accessibility of the sources, the quality of the content, and the content presentation. In particular, some sources such as teachers, families, TV, science magazines, textbooks, and science centers/museums ("directive sources") predictably led students to other sources such as teachers, families, internet, and science books ("directed sources"). A small number of sources crossed context boundaries, being useful in both school and out. Results shed light on the connection between science education and science communication in terms of promoting science learning.

    17. Health-related Quality of Life of Thai children with HIV infection: a comparison of the Thai Quality of Life in Children (ThQLC) with the Pediatric Quality of Life Inventory™ version 4.0 (PedsQL™ 4.0) Generic Core Scales.

      PubMed

      Punpanich, Warunee; Boon-Yasidhi, Vitharon; Chokephaibulkit, Kulkanya; Prasitsuebsai, Wasana; Chantbuddhiwet, Umaporn; Leowsrisook, Pimsiri; Hays, Ron D; Detels, Roger

      2010-12-01

      The purpose of this study was to evaluate the reliability and validity of the Thai Quality of Life in Children (ThQLC) and compare it with the Pediatric Quality of Life Inventory (PedsQL™ 4.0) in a sample of children receiving long-term HIV care in Thailand. The ThQLC and the PedsQL™ 4.0 were administered to 292 children with HIV infection aged 8-16 years. Clinical parameters such as the current viral load, CD4 percent, and clinical staging were obtained by medical record review. Three out of five ThQLC scales and three out of four PedsQL™ 4.0 scales had acceptable internal consistency reliability (i.e., Cronbach's alpha >0.70). Cronbach's alpha values of each scale ranged from 0.52 to 0.75 and 0.57 to 0.75 for the ThQLC and the PedsQL™ 4.0, respectively. Corresponding scales (physical functioning, emotional well-being, social functioning, and school functioning) of the ThQLC and the PedsQL™ 4.0 correlated substantially with one another (r = 0.47, 0.67, 0.59 and 0.56, respectively). Both ThQLC and PedsQL™ 4.0 overall scores significantly correlated with the child's self-rated severity of the illness (r = -0.23 for the ThQLC and -0.28 for the PedsQL™ 4.0) and the caregiver's rated overall quality of life (r = 0.07 for the ThQLC and 0.13 for the PedsQL™ 4.0). The overall score of the ThQLC correlated with clinical and immunologic categories of the United State-Centers for Disease Control and Prevention (US-CDC) classification system (r = -0.12), while the overall score of the PedsQL™ 4.0 significantly correlated with the number of disability days (r = -0.12) and CD4 percent (r = -0.15). However, the overall score from both instruments were not significantly different by clinical stages of HIV disease. A multitrait-multimethod analysis results demonstrated that the average convergent validity and off-diagonal correlations were 0.58 and 0.45, respectively. Discriminant validity was partially supported with 62% of validity diagonal

    18. The Effect of Mathematical Worksheets Based on Multiple Intelligences Theory on the Academic Achievement of the Students in the 4th Grade Primary School

      ERIC Educational Resources Information Center

      Inan, Cemil; Erkus, Serdar

      2017-01-01

      The aim of this research is to examine the effect of Math worksheets based on the Multiple Intelligences Theory on the academic achievement of students in the 4th grade primary school. The sample of the research consists of 64 (32 experimental and 32 control) students who are studying in the 4th grade in a primary school affiliated to the Ministry…

    19. The relevance of TH1 and TH2 cells in immediate and nonimmediate reactions to gelatin-containing vaccine.

      PubMed

      Ohsaki, M; Tsutsumi, H; Kumagai, T; Yamanaka, T; Wataya, Y; Furukawa, H; Kojima, H; Saito, A; Yano, S; Chiba, S

      1999-02-01

      The immune mechanism of gelatin allergy, especially the participation of TH1 and TH2 cells and their cytokine secretion, has not been investigated. We investigated the characteristics of T lymphocytes from patients allergic to gelatin-containing vaccine by secondary in vitro stimulation of circulating mononuclear cells with gelatin. We studied 8 children with a history of immediate-type reactions and 8 with nonimmediate-type reactions after inoculation of gelatin-containing vaccine. The expression of IFN-gamma (TH1 ), IL-2 (TH1 ), IL-4 (TH2 ), and IL-13 (TH2 ) mRNA was examined semiquantitatively by using a reverse transcriptase PCR. IgE antibody to bovine gelatin was measured with the fluorometric ELISA system, and gelatin-specific T-cell responses were detected by an in vitro lymphocyte proliferation assay. Patients with an immediate reaction all had gelatin-specific IgE antibody, whereas others did not. However, all patients exhibited positive T-lymphocyte responses specific to gelatin. Lymphocytes from subjects with nonimmediate-type reactions generally expressed very weak or sometimes no IFN-gamma, IL-2, or IL-13 genes and especially no IL-4 gene. On the other hand, the lymphocytes of subjects with immediate-type reactions significantly expressed not only IL-4 and IL-13 but also IFN-gamma and IL-2 mRNA. Our observations suggest that both gelatin-specific TH2 and TH1 responses are involved in the pathogenesis of the immediate reaction to gelatin. The gelatin-specific IL-4 and/or IL-13 responses consistently observed in patients with an immediate reaction may be associated with the production of gelatin-specific IgE antibody.

    20. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.

      PubMed

      Hegazy, Ahmed N; Peine, Michael; Helmstetter, Caroline; Panse, Isabel; Fröhlich, Anja; Bergthaler, Andreas; Flatz, Lukas; Pinschewer, Daniel D; Radbruch, Andreas; Löhning, Max

      2010-01-29

      Current T cell differentiation models invoke separate T helper 2 (Th2) and Th1 cell lineages governed by the lineage-specifying transcription factors GATA-3 and T-bet. However, knowledge on the plasticity of Th2 cell lineage commitment is limited. Here we show that infection with Th1 cell-promoting lymphocytic choriomeningitis virus (LCMV) reprogrammed otherwise stably committed GATA-3(+) Th2 cells to adopt a GATA-3(+)T-bet(+) and interleukin-4(+)interferon-gamma(+) "Th2+1" phenotype that was maintained in vivo for months. Th2 cell reprogramming required T cell receptor stimulation, concerted type I and type II interferon and interleukin-12 signals, and T-bet. LCMV-triggered T-bet induction in adoptively transferred virus-specific Th2 cells was crucial to prevent viral persistence and fatal immunopathology. Thus, functional reprogramming of unfavorably differentiated Th2 cells may facilitate the establishment of protective immune responses. Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells. Copyright 2010 Elsevier Inc. All rights reserved.

    1. Idaho National Laboratory Quarterly Occurrence Analysis 4th Quarter FY 2016

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Mitchell, Lisbeth Ann

      This report is published quarterly by the Idaho National Laboratory (INL) Quality and Performance Management Organization. The Department of Energy (DOE) Occurrence Reporting and Processing System, as prescribed in DOE Order 232.2, “Occurrence Reporting and Processing of Operations Information,” requires a quarterly analysis of events, both reportable and not reportable, for the previous 12 months. This report is the analysis of 84 reportable events (29 from the 4th quarter fiscal year 2016 and 55 from the prior three reporting quarters), as well as 39 other issue reports (including events found to be not reportable and Significant Category A and Bmore » conditions) identified at INL during the past 12 months (two from this quarter and 37 from the prior three quarters).« less

    2. Expanding Thorium Hydride Chemistry Through Th²⁺, Including the Synthesis of a Mixed-Valent Th⁴⁺/Th³⁺ Hydride Complex.

      PubMed

      Langeslay, Ryan R; Fieser, Megan E; Ziller, Joseph W; Furche, Filipp; Evans, William J

      2016-03-30

      The reactivity of the recently discovered Th(2+) complex [K(18-crown-6)(THF)2][Cp″3Th], 1 [Cp'' = C5H3(SiMe3)2-1,3], with hydrogen reagents has been investigated and found to provide syntheses of new classes of thorium hydride compounds. Complex 1 reacts with [Et3NH][BPh4] to form the terminal Th(4+) hydride complex Cp″3ThH, 2, a reaction that formally involves a net two-electron reduction. Complex 1 also reacts in the solid state and in solution with H2 to form a mixed-valent bimetallic product, [K(18-crown-6)(Et2O)][Cp″2ThH2]2, 3, which was analyzed by X-ray crystallography, electron paramagnetic resonance and optical spectroscopy, and density functional theory. The existence of 3, which formally contains Th(3+) and Th(4+), suggested that KC8 could reduce [(C5Me5)2ThH2]2. In the presence of 18-crown-6, this reaction forms an analogous mixed-valent product formulated as [K(18-crown-6)(THF)][(C5Me5)2ThH2]2, 4. A similar complex with (C5Me4H)(1-) ligands was not obtained, but reaction of (C5Me4H)3Th with H2 in the presence of KC8 and 2.2.2-cryptand at -45 °C produced two monometallic hydride products, namely, (C5Me4H)3ThH, 5, and [K(2.2.2-cryptand)]{(C5Me4H)2[η(1):η(5)-C5Me3H(CH2)]ThH]}, 6. Complex 6 contains a metalated tetramethylcyclopentadienyl dianion, [C5Me3H(CH2)](2-), that binds in a tuck-in mode.

    3. Dorsally exophytic glioblastoma arising from the medulla oblongata in an adult presenting as 4th ventricular mass.

      PubMed

      Das, Kuntal Kanti; Bettaswamy, Guru Prasad; Mehrotra, Anant; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Behari, Sanjay

      2017-01-01

      Brainstem gliomas are relatively rare in adults (<2% of all gliomas). Exophytic gliomas are focal brainstem lesions, which project into the 4 th ventricle or cerebellopontine angles. These exophytic lesions are usually of low-grade histology (pilocytic astrocytoma or ganglioglioma) and have a relatively better outcome compared with brainstem gliomas as a whole. Glioblastoma is the commonest primary glial cell neoplasm and mostly occurs in the supratentorial compartment. It is rather uncommon in the brainstem and seldom has been described as having an exophytic growth pattern. Here we describe an exophytic brainstem glioblastoma arising from the medulla oblongata in a 55-year-old lady who presented with a 4 th ventricular mass, and present a brief review of the literature. Till now, six cases of glioblastoma arising from the medulla oblongata have been reported. So, ours is the seventh such report. To the best of our knowledge, it also happens to be the sixth reported case of dorsally exophytic brainstem glioblastoma till date.

    4. Complete set of invariants of a 4th order tensor: the 12 tasks of HARDI from ternary quartics.

      PubMed

      Papadopoulo, Théo; Ghosh, Aurobrata; Deriche, Rachid

      2014-01-01

      Invariants play a crucial role in Diffusion MRI. In DTI (2nd order tensors), invariant scalars (FA, MD) have been successfully used in clinical applications. But DTI has limitations and HARDI models (e.g. 4th order tensors) have been proposed instead. These, however, lack invariant features and computing them systematically is challenging. We present a simple and systematic method to compute a functionally complete set of invariants of a non-negative 3D 4th order tensor with respect to SO3. Intuitively, this transforms the tensor's non-unique ternary quartic (TQ) decomposition (from Hilbert's theorem) to a unique canonical representation independent of orientation - the invariants. The method consists of two steps. In the first, we reduce the 18 degrees-of-freedom (DOF) of a TQ representation by 3-DOFs via an orthogonal transformation. This transformation is designed to enhance a rotation-invariant property of choice of the 3D 4th order tensor. In the second, we further reduce 3-DOFs via a 3D rotation transformation of coordinates to arrive at a canonical set of invariants to SO3 of the tensor. The resulting invariants are, by construction, (i) functionally complete, (ii) functionally irreducible (if desired), (iii) computationally efficient and (iv) reversible (mappable to the TQ coefficients or shape); which is the novelty of our contribution in comparison to prior work. Results from synthetic and real data experiments validate the method and indicate its importance.

    5. MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes.

      PubMed

      Chuang, Huai-Chia; Tan, Tse-Hua

      2017-01-07

      Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6 + Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

    6. Effects of strenuous exercise on Th1/Th2 gene expression from human peripheral blood mononuclear cells of marathon participants.

      PubMed

      Xiang, Lianbin; Rehm, Kristina E; Marshall, Gailen D

      2014-08-01

      Physical stressors, such as strenuous exercise, can have numerous effects on the human body including the immune system. The aim of this study was to evaluate the gene expression profile of Th1/Th2 cytokines and related transcription factor genes in order to investigate possible immune imbalances before and after a marathon. Blood samples were collected from 16 normal volunteers 24-48 h before and one week after completing a marathon race. Gene expression of Th1 and Th2 related cytokines from human peripheral blood mononuclear cells (PBMC) was analyzed using Human Th1-Th2-Th3 RT(2) Profiler PCR Array and qRT-PCR that measured the transcript levels of 84 genes related to T cell activation. We found that PBMC express a characteristic Th2-like gene profile one week post-marathon compared to pre-marathon. The majority of genes up-regulated one week post-marathon such as IL-4, GATA3, and CCR4 were Th2 associated. For Th1-related genes, CXCR3 and IRF1 were up-regulated one week post-marathon. There was a trend of down-regulation of two Th1 related genes, T-bet and STAT1. Th3-related gene expression patterns did not change in the study. The ratios of both IFN-γ/IL-4 and T-bet/GATA3 gene expressions were significantly lower one week after marathon. These findings suggest that a Th1/Th2 immune imbalance persisted at least 1 week after completion of a marathon which offers a mechanistic rationale for the increased risk of upper respiratory tract infections often reported after strenuous exercise. Copyright © 2014 Elsevier Ltd. All rights reserved.

    7. Effects of the background electrolyte on Th(IV) sorption to muscovite mica

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Schmidt, Moritz; Hellebrandt, Stefan; Knope, Karah E.

      2015-09-01

      The adsorption of tetravalent thorium on the muscovite mica (001) basal plane was studied by X-ray crystal truncation rod (CTR), and resonant anomalous X-ray reflectivity (RAXR) measurements and alpha spectrometry in the presence of perchlorate background electrolytes LiClO 4, NaClO 4, and KClO 4 ([Th(IV)] = 0.1 mM, I = 0.1 M or 0.01 M, pH = 3.3 ± 0.3). RAXR data directly reveal a strong influence of the background electrolyte on the actinide sorption. No significant Th adsorption was observed in 0.1 M NaClO 4, i.e., the Th coverage θ(Th), the number of Th per unit cell area ofmore » the muscovite surface (A UC = 46.72 Å 2), was ≤ 0.01 Th/A UC, whereas limited uptake (θ(Th) ~ 0.04 Th/A UC) was detected at a lower ionic strength (I = 0.01 M). These results are in stark contrast to the behavior of Th in 0.1 M NaCl which showed a coverage of 0.4 Th/A UC (Schmidt et al., 2012a). Th uptake was also influenced by the electrolyte cation. Weak adsorption was observed in 0.1M KClO 4 (θ(Th) ~ 0.07 Th/AUC) similar to the results in NaClO 4 at lower ionic strength. In contrast, strong adsorption was found in 0.1 M LiClO 4, with θ(Th) = 4.9 Th/A UC, a ~10-fold increase compared with that previously reported in NaCl. These differences are confirmed independently by ex situ alpha spectrometry, which shows no measurable Th coverage in 0.1 M NaClO 4 background in contrast to a large coverage of 1.6 Th/A UC in 0.1 M LiClO 4. The CTR/RAXR analyses of Th-LiClO 4 show the sorption structure consisting of Th species that are broadly distributed, centered at heights of 4.1 Å and 29 Å distance from the interface. Neither the very large distribution height of the second species nor the high coverage can be explained with (hydrated) ionic adsorption, suggesting that the enhanced uptake is presumably due to the formation and sorption of Th nanoparticles.« less

    8. Effect of ginseng polysaccharides and dendritic cells on the balance of Th1/Th2 T helper cells in patients with non-small cell lung cancer.

      PubMed

      Ma, Junjie; Liu, Huiping; Wang, Xiaolong

      2014-12-01

      To investigate the effect of thorascopic administration.of ginseng polysaccharides (GPS) plus dendritic cells (DC) on T helper cell type 1/T helper cell type 2 (Th1/Th2) balance in patients with non-small cell lung cancer (NSCLC). A total of 96 NSCLC patients were divided evenly into two groups. The control group was treated with DCs alone and the treatment group was treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically, once a week, 4 times for 30 days, the patients' quality of life was measured with the Functional Assessment of Cancer Treatment-Lung (FACT-L) questionnaire before and after treatment. Serum interferon-γ (INF-γ), interleukin-4 (IL-4), IL-2 and IL-5 were examined before and after treatments. The level of Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 cytokines (INF-γ/IL-4, IL-2/ IL-5) increased in both treatment groups, while Th2 cytokines (IL-4, IL-5) and FACT-L scores decreased (P < 0.01). Furthermore, after treatment Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 cytokines (INF-γ/IL-4, IL-2/IL-5) were higher in the DCs + GPS group than in the control group (P < 0.05). Conversely, FACT-L scores and Th2 cytokines (IL-4, IL-5) were higher in the control group than in the DCs + GPS group (P < 0.05). The treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune function as compared with DCs alone. This was evident by increased expression of Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 (INF-γ/IL-4, IL-2/IL-5), as well as by decreased FACT-L scores and the expression of Th2 cytokines (IL-4, IL-5).

    9. Defense Attache Saigon: RVNAF Quarterly Assessment, 4th Quarter FY74

      DTIC Science & Technology

      1974-08-01

      bombardments with mortars , rockets, and artillery against this outpost and other GVN outposts in the area. Ralliers indicated that elements of the 5th...lery/ mortar fire and mines to stall RVNAF attempts to regain control west of Ben Cat and to inflict casualties. (6) In the Phu Giao area, the 209th and...losses reported were 390 KIA and 12 DTN. Additionally 28 CS, 63 SA, a substantial number of rockets, mortar rounds, AT-3 missiles, mines and other

    10. Self-Reported Reasons for Vaping Among 8th, 10th, and 12th Graders in the US: Nationally-Representative Results

      PubMed Central

      Patrick, Megan E.; Miech, Richard A.; Carlier, Carola; O’Malley, Patrick M.; Johnson, Lloyd D.; Schulenberg, John E.

      2016-01-01

      Objective The study describes the most common reasons for using vaporizers (such as e-cigarettes) among US adolescents and investigates how reasons for use differ by grade, lifetime cigarette use, frequency of vaporizer use, gender, race/ethnicity, and parent education. Method Data were collected from 4,066 students in the 8th, 10th, and 12th grades in 2015 as part of the Monitoring the Future study, a cross-sectional and nationally representative US survey Results Common reasons for vaporizer use reported by respondents who had ever used a vaporizer were experimentation (53.0%), taste (37.2%), boredom (23.5%), having a good time (22.4%), and relaxation (21.6%). Reasons differed little across grades or parent education; reasons differed by lifetime use of regular cigarettes, frequency of vaping, gender, and race/ethnicity. Conclusions Overall, results suggest that decisions to vape are based on curiosity, taste, and pleasure, rather than for reasons such as quitting regular cigarettes or substituting for regular cigarette smoking. PMID:27286951

    11. The influence of hydro-ethanolic extract of Portulaca oleracea L. on Th1/Th2 balance in isolated human lymphocytes.

      PubMed

      Askari, Vahid Reza; Rezaee, Seyed Abdolrahim; Abnous, Khalil; Iranshahi, Mehrdad; Boskabady, Mohammad Hossein

      2016-12-24

      The anti-inflammatory and anti-oxidants activity of Portulaca oleracea L. (P. oleracea) were mentioned in traditional texts. In previous studies, different anti-inflammatory and anti-oxidant effects of P. oleracea were demonstrated. However, the mechanism of action and immunomodulatory property of this plant are greatly unknown. In the present study, the effect of the extract of this plant on IL-4, IL10, IFN-γ and T helper (h)1/Th2 balance in non-stimulated and stimulated human lymphocytes was examined. The effect of three concentrations (160, 40 and 10µg/ml) of P. oleracea or dexamethasone were evaluated on percentage of cell proliferation and nitric oxide (NO) production as well as secretion of cytokines (IL-4, IL10 and IFN-γ) in PHA-stimulated and non-stimulated lymphocytes, and compared to control and dexamethasone as positive control (n=15 for each group). In stimulated cells, dexamethasone significantly inhibited the percentage of cell proliferation, NO production, and secretion of cytokines in comparison to control group (P<0.001 for all cases). The percentage of cell proliferation, NO production, and secretion of cytokines were significantly decreased while Th1/Th2 (IFN-γ/IL-4) and Treg/Th2 (IL-10/IL-4) balances significantly enhanced in treated groups with all three concentrations of extract compared to control group (P<0.001 for all cases). The effect of all concentrations of the extract on cell proliferation, NO production and secretion of cytokines as well as Treg/Th2 balance were significantly lower than dexamethasone (P<0.001 for all cases), but Th1/Th2 ratio obtained in the presence of only low extract concentration was lower than dexamethasone (P<0.01). Different concentrations of extract promoted Th1/Th2 and Treg/Th2 balances which may suggest the therapeutic value of the plant in inflammatory disease associated with decreased Th1/Th2 balance such as asthma or cancers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

    12. Virus Infection Stages and Distinct Th1 or Th17/Th22 T-Cell Responses in Malaria/SHIV Coinfection Correlate with Different Outcomes of Disease

      PubMed Central

      Ryan-Payseur, Bridgett; Ali, Zahida; Huang, Dan; Chen, Crystal Y.; Yan, Lin; Wang, Richard C.; Collins, William E.; Wang, Yunqi

      2011-01-01

      Background. Malaria and AIDS represent 2 leading causes of death from infectious diseases worldwide, and their high geographic overlap means coinfection is prevalent. It remains unknown whether distinct immune responses during coinfection with malaria and human immunodeficiency virus (HIV) affect clinical outcomes. Methods. We tested this hypothesis by employing macaque models of coinfection with malaria and simian-human immunodeficiency virus (SHIV). Results. Plasmodium fragile malaria coinfection of acutely SHIV-infected macaques induced hyperimmune activation and remarkable expansion of CD4+ and CD8+ T effector cells de novo producing interferon γ or tumor necrosis factor α. Malaria-driven cellular hyperactivation/expansion and high-level Th1-cytokines enhanced SHIV disease characterized by increasing CD4+ T-cell depletion, profound lymphoid depletion or destruction, and even necrosis in lymph nodes and spleens. Importantly, malaria/SHIV-mediated depletion, destruction, and necrosis in lymphoid tissues led to bursting parasite replication and fatal virus-associated malaria. Surprisingly, chronically SHIV-infected macaques without AIDS employed different defense mechanisms during malaria coinfection, and mounted unique ∼200-fold expansion of interleukin 17+/interleukin 22+ T effectors with profound Th1 suppression. Such remarkable expansion of Th17/Th22 cells and inhibition of Th1 response coincided with development of immunity against fatal virus-associated malaria without accelerating SHIV disease. Conclusions. These novel findings suggest that virus infection status and selected Th1 or Th17/Th22 responses after malaria/AIDS-virus coinfection correlate with distinct outcomes of virus infection and malaria. PMID:21921207

    13. Metal ring on 4th or 5th finger markedly increases both cardiac troponin I at left ventricle and cancer-related parameters such as oncogen C-fosAb2 & integrin α₅β₁[corrected] by 4-12 times. Thus these metal rings appear to promote both heart problems & cancer.

      PubMed

      Omura, Yoshiaki; Hines, Howard; Jones, Marilyn; O'Young, Brian; Duvvi, Harsha; Lu, Dominic P; Pallos, Andrew; Shimotsuura, Yasuhiro; Ohki, Motomu

      2010-01-01

      We examined patients wearing a metal ring on the left 4th finger with abnormally increased Cardiac Troponin I (which is known to increase in the presence of myocardial injury or left ventricular hypertrophy) of 5-14ng BDORT units (depending on the ring and individual) at left ventricle compared with normal value of 1ng BDORT units or less. Although shape of the ECG does not change significantly regardless of whether metal rings are on or not, when rings are on, the Bi-Digital O-Ring Test evaluation of trace of ECG revealed "Vulnerable Period of Rising Part of T-wave" of ECG waves (which correspond to the left ventricle and AV node) become abnormal with increased Cardiac Troponin I. DHEA in various parts of the body reduced significantly and maximum decrease in DHEA was found when metal ring was on the left 4th and 5th fingers. Telomere reduced with each of the 5 fingers, but the 2nd, 4th, and 5th fingers produced the maximum reduction of telomere. When metal ring was inserted onto the left 1st finger and left 2nd finger, Cardiac Troponin I did not change significantly. Additional abnormality was found when patients with cancer wore metal ring(s); namely both Cardiac Troponin I and cancer parameters, such as Integrin α₅β₁[corrected] and Oncogen C-fos Ab2, increase anywhere between 4-12 times. However, when the ring was cut, creating a 1mm or longer empty space, no increase in cancer markers and Cardiac Troponin I were observed. Similar findings were found with metal bracelets.

    14. Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

      PubMed Central

      Li, Wenpeng; Guo, Linjie; Rathi, Purva; Marinova, Ekaterina; Gao, Xiuhua; Wu, Meng-Feng; Liu, Hao; Dotti, Gianpietro; Gottschalk, Stephen; Metelitsa, Leonid S.; Heczey, Andras

      2017-01-01

      T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). All GPC3-CARs rendered T cells highly cytotoxic to GPC3-positive hepatocellular carcinoma, hepatoblastoma, and malignant rhabdoid tumor cell lines in vitro. GBBz induced the preferential production of Th1 cytokines (interferon γ/granulocyte macrophage colony-stimulating factor) while G28z preferentially induced Th2 cytokines (interleukin-4/interleukin-10). Inclusion of 4-1BB in G28BBz could only partially ameliorate the Th2-polarizing effect of CD28. 4-1BB induced superior expansion of CAR T cells in vitro and in vivo. T cells expressing GPC3-CARs incorporating CD28, 4-1BB, or both induced sustained tumor regressions in two xenogeneic tumor models. Thus, GBBz CAR endows T cells with superior proliferative potential, potent antitumor activity, and a Th1-biased cytokine profile, justifying further clinical development of GBBz CAR for immunotherapy of GPC3-positive solid tumors. PMID:27530312

    15. Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice.

      PubMed

      Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

      2016-11-14

      To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. Treg cells, Treg cell subsets, Th17 cells, and CD4 + CD25 + FoxP3 + IL-17 + cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased ( P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4 + CD45RA + FoxP3 low ) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4 + CD45RA - FoxP3 high ) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4 + CD45RA - FoxP3 low ) and CD4 + CD25 + FoxP3 + IL-17A + cells was increased. FoxP3 mRNA levels in CD4 + CD45RA - FoxP3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4 + CD45RA - FoxP3 high , and CD4 + CD45RA - FoxP3 low cells was higher in LPC relative to other tissues. Increased numbers of CD4 + CD45RA - FoxP3 low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

    16. Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice

      PubMed Central

      Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

      2016-01-01

      AIM To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. METHODS Treg cells, Treg cell subsets, Th17 cells, and CD4+CD25+FoxP3+IL-17+ cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. RESULTS In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4+CD45RA+FoxP3low) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4+CD45RA-FoxP3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4+CD45RA-FoxP3low) and CD4+CD25+FoxP3+IL-17A+ cells was increased. FoxP3 mRNA levels in CD4+CD45RA-FoxP3low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP3high, and CD4+CD45RA-FoxP3low cells was higher in LPC relative to other tissues. CONCLUSION Increased numbers of CD4+CD45RA-FoxP3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues. PMID:27895423

    17. Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial

      PubMed Central

      d'Ettorre, Gabriella; Baroncelli, Silvia; Micci, Luca; Ceccarelli, Giancarlo; Andreotti, Mauro; Sharma, Prachi; Fanello, Gianfranco; Fiocca, Fausto; Cavallari, Eugenio Nelson; Giustini, Noemi; Mallano, Alessandra; Galluzzo, Clementina M.; Vella, Stefano; Mastroianni, Claudio M.; Silvestri, Guido; Paiardini, Mirko; Vullo, Vincenzo

      2014-01-01

      Introduction During HIV infection the severe depletion of intestinal CD4+ T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4+ T-cell subsets reconstitution under combined antiretroviral therapy (cART), and systemic immune activation markers. Methods This longitudinal single-arm pilot study evaluates CD4+ T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0) and after eight (M8) months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4+ T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4+ Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS) and PCR Real Time to detect plasma bacterial 16S rDNA. Results Eight months of cART increased intestinal CD4+ and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4+ T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4+ T-cell recovery. Conclusion Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4+ T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4+ and of CD8+ T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals. Trial Registration ClinicalTrials.gov NCT02097381 PMID:25340778

    18. TET1 and TET3 are essential in induction of Th2-type immunity partly through regulation of IL-4/13A expression in zebrafish model.

      PubMed

      Yang, Chao; Li, Zhuo; Kang, Wei; Tian, Yu; Yan, Yuzhu; Chen, Wei

      2016-10-10

      It has been considered that epigenetic modulation can affect a diverse array of cellular activities, in which ten eleven translocation (TET) methylcytosine dioxygenase family members refer to a group of fundamental components involved in catalyzation of 5-hydroxymethylcytosine and modification of gene expression. Even though the function of TET proteins has been gradually revealed, their roles in immune regulation are still largely unknown. Recent studies provided clues that TET2 could regulate several innate immune-related inflammatory mediators in mammals. This study sought to explore the function of TET family members in potential T-helper (Th) cell differentiation involved in adaptive immunity by utilizing a zebrafish model. As shown by results, soluble antigens could induce expression of zebrafish IL-4/13A (i.e. a pivotal Th2-type cytokine essential in Th2 cell differentiation and functions), and further trigger the expression of Th1- and Th2-related genes. It is noteworthy that this response was accompanied by the up-regulation of two TET family members (TET1 and TET3) both in immune organs (spleen and kidney) and cells (peripheral lymphocytes). Knocking-down of TET1 and TET3 will give rise to the decreased responses of IL-4/13A induction against exogenous soluble antigen stimulation, and further restrain the expression of Th2-related genes, which indicates a restrained Th2 cell differentiation. Nonetheless, TET2 did not exhibit effect on the modification of Th1/Th2 related gene expression. Hence, these data showed that TET1 and TET3 might be two significant epigenetic regulators involved in Th2 differentiation through regulation of IL-4/13A expression. This is the first report to show that TET family members play indispensable roles in Th2-type immunity, indicating an epigenetic modulation manner involved in adaptive immune regulations and responses. Copyright © 2016 Elsevier B.V. All rights reserved.

    19. High surface area ThO/sub 2/ catalyst

      DOEpatents

      Colmenares, C.A.; Somorjai, G.A.; Maj, J.J.

      1983-06-21

      A ThO/sub 2/ catalyst having a high surface area of about 80 to 125m/sup 2//g is synthesized. The compound is synthesized by simultaneously mixing an aqueous solution of ThNO/sub 3/(NO/sub 3/)/sub 4/.4H/sub 2/O with an aqueous solution of Na/sub 2/CO/sub 3/.H/sub 2/O, to produce a solution and solid ThOCO/sub 3/. The solid ThOCO/sub 3/ is separated from the solution, and then calcined at a temperature of about 225 to 300/sup 0/C for about 40 to 55 hours to produce ThO/sub 2/. The ThO/sub 2/ catalyst produced includes Na present as a substitutional cation in an amount equal to about 5 to 10 at. %.

    20. Aberrant Production of Th1/Th2/Th17-Related Cytokines in Serum of C57BL/6 Mice after Short-Term Formaldehyde Exposure

      PubMed Central

      Wei, Haiyan; Tan, Kehong; Sun, Rongli; Yin, Lihong; Zhang, Juan; Pu, Yuepu

      2014-01-01

      Previous studies have shown that formaldehyde (FA) could cause immunotoxicity by changing the number of T lymphocytes and that cytokines play a pivotal role in the regulation of T lymphocytes. However, the previously used cytokine detection methods are difficult to use in the measurement of several cytokines in a small amount of sample for one test. Therefore, the cytometric bead array (CBA) technique was used. CBA showed better analytical efficiency and sensitivity than the previous methods. C57BL/6 mice were exposed to the control (normal saline), low FA concentration (0.5 mg/kg), and high FA concentration (2 mg/kg) for 1 week or 1 month. The contents of cytokines, including Th1-related cytokines (IL-2, IFN-γ, and tumor necrosis factor), Th2-related cytokines (IL-4, IL-6, and IL-10), and Th17-related cytokines (IL-17A), were measured by using the BD FACS Canto II Flow Cytometer and analyzed by FCAP ArrayTM Software. Th1/Th2/Th17-related cytokines showed a slightly decreasing trend after low FA exposure. Conversely, a significantly increasing trend was found after high FA exposure. Th1/Th2/Th17-related cytokines all serve important functions in the immune reactions in mice after FA exposure. PMID:25264680

    1. Report of the 4th World Climate Research Programme International Conference on Reanalyses

      NASA Technical Reports Server (NTRS)

      Bosilovich, Michael G.; Rixen, Michel; van Oevelen, Peter; Asrar, Ghassem; Compo, Gilbert; Onogi, Kazutoshi; Simmons, Adrian; Trenberth, Kevin; Behringer, Dave; Bhuiyan, Tanvir Hossain; hide

      2012-01-01

      The 4th WCRP International Conference on Reanalyses provided an opportunity for the international community to review and discuss the observational and modelling research, as well as process studies and uncertainties associated with reanalysis of the Earth System and its components. Characterizing the uncertainty and quality of reanalyses is a task that reaches far beyond the international community of producers, and into the interdisciplinary research community, especially those using reanalysis products in their research and applications. Reanalyses have progressed greatly even in the last 5 years, and newer ideas, projects and data are coming forward. While reanalysis has typically been carried out for the individual domains of atmosphere, ocean and land, it is now moving towards coupling using Earth system models. Observations are being reprocessed and they are providing improved quality for use in reanalysis. New applications are being investigated, and the need for climate reanalyses is as strong as ever. At the heart of it all, new investigators are exploring the possibilities for reanalysis, and developing new ideas in research and applications. Given the many centres creating reanalyses products (e.g. ocean, land and cryosphere research centres as well as NWP and atmospheric centers), and the development of new ideas (e.g. families of reanalyses), the total number of reanalyses is increasing greatly, with new and innovative diagnostics and output data. The need for reanalysis data is growing steadily, and likewise, the need for open discussion and comment on the data. The 4th Conference was convened to provide a forum for constructive discussion on the objectives, strengths and weaknesses of reanalyses, indicating potential development paths for the future.

    2. 4th generation HIV screening in Massachusetts: a partnership between laboratory and program.

      PubMed

      Goodhue, Tammy; Kazianis, Arthur; Werner, Barbara G; Stiles, Tracy; Callis, Barry P; Dawn Fukuda, H; Cranston, Kevin

      2013-12-01

      The Massachusetts Department of Public Health's (MDPH) Office of HIV/AIDS (OHA) and Hinton State Laboratory Institute (HSLI) have offered HIV screening since 1985. Point-of-care screening and serum collection for laboratory-based testing is conducted at clinic and non-clinic-based sites across Massachusetts as part of an integrated communicable disease screening intervention. MDPH aimed to transition to a 4th generation HIV screening-based algorithm for testing all serum specimens collected at OHA-funded programs and submitted to the HSLI to detect acute HIV infections, detect and differentiate HIV-1 and HIV-2 infections, eliminate indeterminate results, reduce cost and turnaround time, and link newly diagnosed HIV+ individuals to care. The HSLI and OHA created a joint project management team to plan and lead the transition. The laboratory transitioned successfully to a 4th generation screening assay as part of a revised diagnostic algorithm. In the 12 months since implementation, a total of 7984 serum specimens were tested with 258 (3.2%) positive for HIV-1 and one positive for HIV-2. Eight were reported as acute HIV-1 infections. These individuals were linked to medical care and partner services in a timely manner. Turnaround time was reduced and the laboratory realized an overall cost savings of approximately 15%. The identification of eight acute HIV infections in the first year underscores the importance of using the most sensitive screening tests available. A multi-disciplinary program and laboratory team was critical to the success of the transition, and the lessons learned may be useful for other jurisdictions. Published by Elsevier B.V.

    3. Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

      PubMed

      Nasr, Amre; Abushouk, Amir; Hamza, Anhar; Siddig, Emmanuel; Fahal, Ahmed H

      2016-07-01

      Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2) were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10) were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

    4. Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.

      PubMed

      Uchiyama, Ryosuke; Yonehara, Shin; Taniguchi, Shun'ichiro; Ishido, Satoshi; Ishii, Ken J; Tsutsui, Hiroko

      2017-08-01

      CD4 + Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4 + Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard -/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas -/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas -/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. Copyright © 2017 by The American Association of Immunologists

    5. The Effects of Teaching Reading Using the Gradual Release of Responsibility Model and 4th Grade Reading

      ERIC Educational Resources Information Center

      Young, Marthel I.

      2017-01-01

      Students' inability to meet grade level standards in reading on state and national assessments continues to be a problem across the nation. This causal comparative cohort model sought to examine the effect of the Gradual Release of Responsibility Model (GRRM) on 4th grade reading achievement, gender, and socio-economic status, and to examine…

    6. Using Inquiry-Based Instruction to Teach Research Methods to 4th-Grade Students in an Urban Setting

      ERIC Educational Resources Information Center

      Hamm, Ellen M.; Cullen, Rebecca; Ciaravino, Melissa

      2013-01-01

      When a college professor who teaches research methods to graduate education students was approached by a local public urban elementary school to help them teach research skills to 4th-graders, it was thought that the process would be simple--take what we did at the college level and differentiate it for the childhood classroom. This article will…

    7. The Th1-promoting effects of dehydroepiandrosterone can provide an explanation for the stronger Th1-immune response of women.

      PubMed

      Namazi, Mohammad Reza

      2009-03-01

      Estrogens foster immunological processes driven by CD4+ Th2 cells and B cells and androgens foster Th1 CD4+ and CD8+ cell activity. Higher levels of IFN-gamma and IL-2 and lower levels of IL-4 and IL-10 are detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women. It is documented that the physiologic levels of estrogens produced during the luteal phase of the menstrual cycle shift the female immune system toward a Th2-type response and that the Th1 cytokines are increased in postmenopausal women. However, the Th1 immune response is also surprisingly stronger in women, hence affording them a better protection against infections. Nickel sensitivity, a Th1 immune reaction, seems to be more common in women even if men wear earrings. Further, not only the Th2 but also the Th1 autoimmune diseases are generally more common in women than men. How do women advance a stronger Th1 response than men? It is suggested that in contrast to the paradigm that estrogens lead to a Th2 bias, estrogens can enhance Th1 cytokine production also. However, the discrepant effects of estrogens are difficult to be reconciled from a molecular viewpoint and hence are not advocated by all authors. This paper provides an explanation: The effects of dehydroepiandrosterone on Th1/Th2 balance seem to be model-specific; in humans dehydroepiandrosterone, represents a pivotal up-regulator of Th1 immune response. Steroid sulphatase is a microsomal enzyme that cleaves the sulphate group of dehydroepiandrosterone sulphate. This enzyme is controlled by an X-linked gene that escapes the Lyon effect of X-inactivation; as a result, women usually have about twice steroid sulphatase in their cells, including macrophages, as have men. Putting all these facts together, it could be concluded that women's macrophages, which contain higher steroid sulphatase levels and enter peripheral lymphoid organs through afferent lymphatic drainage, produce higher levels of

    8. Altered chemokine Th1/Th2 balance in Addison's disease: relationship with hydrocortisone dosing and quality of life.

      PubMed

      Ekman, B; Alstrand, N; Bachrach-Lindström, M; Jenmalm, M C; Wahlberg, J

      2014-01-01

      The adrenalitis found in autoimmune Addison's disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33-56) pg/ml vs. 22 (19-34) pg/ml, p<0.01] and CXCL11 [37 (29-48) pg/ml vs. 16 (9-24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life. © Georg Thieme Verlag KG Stuttgart · New York.

    9. Effectiveness of fenbendazole against later 4th-stage Strongylus vulgaris in ponies.

      PubMed

      Slocombe, J O; McCraw, B M; Pennock, P W; Baird, J D

      1983-12-01

      Twelve pony foals (reared worm-free) were inoculated with Strongylus vulgaris. Approximately 8 weeks later, 4 of the foals were given fenbendazole (10% suspension) at a dosage rate of 10 mg/kg of body weight daily for 5 days and 4 foals were given the suspension at a dosage rate of 50 mg/kg daily for 3 days; the remaining foals were given a placebo. All treatments were administered by stomach tube. Fenbendazole was 99.6 and 97.9% effective in the 2 treatment groups, respectively, in eliminating later 4th-stage S vulgaris larvae located near the origin of major intestinal arteries. On microscopic examination of the ileocolic artery from fenbendazole-treated foals, a few larval remnants were found beneath the tunica intima in small organized mural thrombi overgrown with endothelium. It would appear that larvae are rapidly destroyed after administration of fenbendazole. A pony foal reared on pasture and with arteriographic evidence of arteritis of the cranial mesenteric and ileocolic arteries was treated with fenbendazole (10% suspension) by stomach tube at a dosage rate of 50 mg/kg of body weight daily for 3 days. By arteriographic examination made 4 weeks later, there was evidence of regression of the lesion, and at necropsy done a week later, there was no arteritis or larvae in the lumen of those arteries.

    10. A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-κB signaling independent of MyD88/TRIF and promotes Th2 response.

      PubMed

      Wu, Xianzhu; Gowda, Nagaraj M; Kawasawa, Yuka I; Gowda, D Channe

      2018-04-17

      Dendritic cells (DC) and cytokines produced by DC play crucial roles in inducing and regulating pro-/anti-inflammatory and Th1/Th2 responses. DC are known to produce Th1-promoting cytokine, IL-12, in response to malaria and other pathogenic infections, but it is thought that DC do not produce Th2-promoting cytokine, IL-4. Here, we show that a protein factor of malaria parasites induces IL-4 responses by CD11c hi MHCII hi CD3ε - CD49b - CD19 - FcεRI - DC via PI3K-Akt-NF-κB signaling independent of TLR-MyD88/TRIF. Malaria parasite-activated DC induced IL-4 responses by T cells both in vitro and in vivo , favoring Th2, and il-4 deficient DC were unable to induce IL-4 expression by T cell.  Interestingly, lethal parasites, Plasmodium falciparum and P. berghei ANKA, induced IL-4 response primarily by CD8a - DC, whereas nonlethal P. yoelii induced IL-4 by both CD8α + and CD8α - DC. In both P. berghei ANKA- and P. yoelii -infected mice, IL-4-expressing CD8α - DC did not express IL-12, but a distinct CD8α - DC subset expressed IL-12. In P. berghei ANKA infection, CD8α + DC expressed IL-12 but not IL-4, whereas in P. yoelii infection CD8α + DC expressed IL-4 but not IL-12. This differential IL-4 and IL-12 responses by DC subsets may contribute to different Th1/Th2 development and clinical outcomes in lethal and nonlethal malaria. Our results for the first time demonstrate that a malaria protein factor induces IL-4 production by DC via PI3K-Akt-NF-κB signaling, revealing signaling and molecular mechanisms that initiate and promote Th2 development. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

    11. Th2 Allergic Immune Response to Inhaled Fungal Antigens is Modulated By TLR-4-Independent Bacterial Products

      PubMed Central

      Allard, Jenna B.; Rinaldi, Lisa; Wargo, Matt; Allen, Gilman; Akira, Shizuo; Uematsu, Satoshi; Poynter, Matthew E.; Hogan, Deborah A.; Rincon, Mercedes; Whittaker, Laurie A.

      2009-01-01

      SUMMARY Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well know triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4-independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response, and potentially impact the development of allergic airway disease to environmental fungal antigens. PMID:19224641

    12. Seismically induced liquefaction structures in La Magdalena archaeological site, the 4th century AD Roman Complutum (Madrid, Spain)

      NASA Astrophysics Data System (ADS)

      Rodríguez-Pascua, M. A.; Silva, P. G.; Perucha, M. A.; Giner-Robles, J. L.; Heras, C.; Bastida, A. B.; Carrasco, P.; Roquero, E.; Lario, J.; Bardaji, T.; Pérez-López, R.; Elez, J.

      2016-10-01

      The ancient Roman city of Complutum (Alcalá de Henares, Madrid), founded in the 1st century AD, was one of the most important cities of Hispania. The old Roman city was destroyed, abruptly abandoned, relocated close by and rebuilt during the late 4th century AD. Destruction of the city and its relocation has not yet been explained by archaeologists. In this paper, with our multidisciplinary approach, we identify and characterize earthquake archaeological effects (EAEs) affecting the archaeological site, the La Magdalena, an agricultural holding 4 km from the core of Complutum. The most important EAEs in the site are liquefactions (sand dikes and explosive sand-gravel craters) affecting Roman structures, such as water tanks (cisterns), houses and graves. Ground liquefaction generated significant ground cracks, explosive craters and folds in foundations of buildings. Several other Roman sites throughout the valley were also abandoned abruptly during the 4th century AD, in some cases with EAEs of similar origin. This suggests the occurrence of a 5.0-6.6 Mw seismic event in the zone, in accordance with the minimum empirical limit of seismically-induced liquefaction and the maximum surface rupture length of the Henares fault.

    13. U and Th isotope constraints on the duration of Heinrich events H0-H4 in the southeastern Labrador Sea

      NASA Astrophysics Data System (ADS)

      Veiga-Pires, C. C.; Hillaire-Marcel, C.

      1999-04-01

      The duration and sequence of events recorded in Heinrich layers at sites near the Hudson Strait source area for ice-rafted material are still poorly constrained, notably because of the limit and uncertainties of the 14C chronology. Here we use high-resolution 230Th-excess measurements, in a 6 m sequence raised from Orphan Knoll (southern Labrador Sea), to constrain the duration of the deposition of the five most recent Heinrich (H) layers. On the basis of maximum/minimum estimates for the mean glacial 230Th-excess flux at the studied site a minimum/maximum duration of 1.0/0.6, 1.4/0.8, 1.3/0.8, 1.5/0.9, and 2.1/1.3 kyr is obtained for H0 (˜Younger Dryas), Hl, H2, H3, and H4, respectively. Thorium-230-excess inventories and other sedimentological features indicate a reduced but still significant lateral sedimentary supply by the Western Boundary Undercurrent during the glacial interval. U and Th series systematics also provide insights into source rocks of H layer sediments (i.e., into distal Irminger Basin/local Labrador Sea supplies).

    14. IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

      PubMed

      Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

      2018-01-01

      The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

    15. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Fukuyama, Yoshiko; Tokuhara, Daisuke; Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639

      Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FLmore » activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.« less

    16. Probing the Influence of Acidity and Temperature to Th(IV) on Hydrolysis, Nucleation, and Structural Topology.

      PubMed

      Lin, Jian; Qie, Meiying; Zhang, Linjuan; Wang, Xiaomei; Lin, Yuejian; Liu, Wei; Bao, Hongliang; Wang, Jianqiang

      2017-11-20

      Systematic control of the molar ratio between thorium hydroxides and selenic acid and their reaction temperature under hydrothermal conditions results in four novel thorium-based selenate complexes, namely, [Th 8 O 4 (OH) 8 (SeO 4 ) 6 (H 2 O) 16 ]·(SeO 4 ) 2 ·13H 2 O (Th-1), [Th 8 O 4 (OH) 8 (SeO 4 ) 8 (H 2 O) 13 ]·7H 2 O (Th-2), Th(OH) 2 (SeO 4 )H 2 O (Th-3), and Th 3 (SeO 4 ) 6 (H 2 O) 6 ·2.5H 2 O (Th-4), as well as the thorium mixed selenite selenate compound Th(SeO 3 )(SeO 4 ) (Th-5). Smaller [H 2 SeO 4 ]/[Th(IV)] ratio or lower temperature give rise to the formation of octameric [Th 8 (μ 3 -O) 4 (μ 2 -OH) 8 ] 16+ cores in Th-1/Th-2 and infinite [Th(μ 2 -OH) 2 H 2 O] 2+ chains in Th-3, respectively. Increasing the [H 2 SeO 4 ]/[Th(IV)] ratio or elevating the temperature generates a microporous (11.3 Å voids) open-framework Th-4, a monomeric thorium species without oxo/hydroxyl ligands, and a three-dimensional thorium structure Th-5. Formation of these compounds suggests that variables including acidity and temperature play a critical role in the hydrolysis and oligomerization of Th IV ions. Increasing acidity limits the deprotonation of water molecules and formation of nucleophilic hydroxo/oxo-aquo Th species, and high temperature appears to suppress the olation/oxolation hydrolysis reactions, which in both ways limit the formation of the thorium oligomers.

    17. The expanding universe of T-cell subsets: Th1, Th2 and more.

      PubMed

      Mosmann, T R; Sad, S

      1996-03-01

      Since their discovery nearly ten years ago, T helper 1 (Th1) and Th2 subsets have been implicated in the regulation of many immune responses. In this article, Tim Mosmann and Subash Sad discuss the increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy.

    18. Investigation of Academic Success, Self-Esteem and Academic Self-Concept in 4th Class Primary School Students

      ERIC Educational Resources Information Center

      Çetinkaya, Seher

      2017-01-01

      In Turkey due to changes in the age starting school implemented during the 2012-2013 academic year, children ages from 60 months to 84 months were subject to the same educational program in the same class. By the 2015-2016 academic year these children were at the end of 4th class. This research aimed to investigate the Turkish and mathematic…

    19. Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1/Th17 and Th2 in Multiple Sclerosis Patients.

      PubMed

      Wu, Qi; Wang, Qin; Mao, Guangmei; Dowling, Catherine A; Lundy, Steven K; Mao-Draayer, Yang

      2017-04-15

      Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4-6 and 18-26 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry. The absolute numbers of CD4 and CD8 T cells were significantly decreased and the CD4/CD8 ratio was increased with DMF treatment. The proportions of both effector memory T cells and central memory T cells were reduced, whereas naive T cells increased in treated patients. T cell activation was reduced with DMF treatment, especially among effector memory T cells and effector memory RA T cells. Th subsets Th1 (CXCR3 + ), Th17 (CCR6 + ), and particularly those expressing both CXCR3 and CD161 were reduced most significantly, whereas the anti-inflammatory Th2 subset (CCR3 + ) was increased after DMF treatment. A corresponding increase in IL-4 and decrease in IFN-γ and IL-17-expressing CD4 + T cells were observed in DMF-treated patients. DMF in vitro treatment also led to increased T cell apoptosis and decreased activation, proliferation, reactive oxygen species, and CCR7 expression. Our results suggest that DMF acts on specific memory and effector T cell subsets by limiting their survival, proliferation, activation, and cytokine production. Monitoring these subsets could help to evaluate the efficacy and safety of DMF treatment. Copyright © 2017 by The American Association of Immunologists, Inc.

    20. T-bet Down-Modulation in Tolerized Th1 Effector CD4 Cells Confers a TCR-Distal Signaling Defect That Selectively Impairs IFN-γ Expression1

      PubMed Central

      Long, Meixiao; Slaiby, Aaron M.; Hagymasi, Adam T.; Mihalyo, Marianne A.; Lichtler, Alexander C.; Reiner, Steven L.; Adler, Adam J.

      2010-01-01

      When Th1 effector CD4 cells encounter tolerizing Ag in vivo, their capacity to express the effector cytokines IFN-γ and TNF-α is lost more rapidly than noneffector functions such as IL-2 production and proliferation. To localize the relevant intracellular signaling defects, cytokine expression was compared following restimulation with Ag vs agents that bypass TCR-proximal signaling. IFN-γ and TNF-α expression were both partially rescued when TCR-proximal signaling was bypassed, indicating that both TCR-proximal and -distal signaling defects impair the expression of these two effector cytokines. In contrast, bypassing TCR-proximal signaling fully rescued IL-2 expression. T-bet, a transcription and chromatin remodeling factor that is required to direct the differentiation of naive CD4 cells into IFN-γ -expressing Th1 effectors, was partially down-modulated in tolerized Th1 effectors. Enforcing T-bet expression during tolerization selectively rescued the ability to express IFN-γ, but not TNF-α. Conversely, expression of a dominant-negative T-bet in Th1 effectors selectively impaired the ability to express IFN-γ, but not TNF-α. Analysis of histone acetylation at the IFN-γ promoter further suggested that down-modulation of T-bet expression during Th1 effector CD4 cell tolerization does not impair IFN-γ expression potential through alterations in chromatin structure. PMID:16393991

    1. Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome.

      PubMed

      Gong, Ping; Shi, Bingwei; Wang, Juan; Cao, Peixia; Diao, Zhenyu; Wang, Yuji; Hu, Yali; Li, Shuping

      2018-02-15

      This study aimed to investigate the Th1/Th2 cells in peripheral blood of PCOS patients, and assess the potential correlation between Th1/Th2 imbalance and obesity. Thirty-nine PCOS patients and 23 age-matched controls were enrolled. The PBMCs were obtained before pharmacological intervention in women with or without PCOS. The profiles of Th1 (IFN-γ) and Th2 (IL-4) cytokines of CD3 + CD - T lymphocyte subsets were analyzed by flow cytometry. Plasma sex hormones including E 2 , T, FSH, LH, and FINS, FPG were measured, together with BMI, WC, LH/FSH, E 2 /T and HOMA-IR index being calculated. Association between Th1/Th2 imbalance and BMI, WC were evaluated. The proportion of Th1 cells and Th1/Th2 ratio were significantly higher in PCOS patients than those in controls, accompanied by elevated T, LH, LH/FSH, FINS, HOMA-IR index and reduced E 2 /T. The Th1/Th2 ratio was increased when BMI and WC were enhanced in PCOS. Moreover, the significant difference of Th1/Th2 ratio was observed between WC subgroups of PCOS. It is concluded that Th1 type immunity is predominant in systemic immunization of PCOS patients. Th1/Th2 immune imbalance is connected with obesity, especially abdominal obesity, and may be one of the underlying mechanism for the pathogenesis of PCOS.

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

      PubMed Central

      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

    3. Nitric oxide enhances Th9 cell differentiation and airway inflammation

      PubMed Central

      Niedbala, Wanda; Besnard, Anne-Gaelle; Nascimento, Daniele Carvalho; Donate, Paula Barbim; Sonego, Fabiane; Yip, Edwin; Guabiraba, Rodrigo; Chang, Hyun-Dong; Fukada, Sandra Y.; Salmond, Robert J.; Schmitt, Edgar; Bopp, Tobias; Ryffel, Bernhard; Liew, Foo Y.

      2014-01-01

      Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4+ T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2−/− mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared to wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells. PMID:25099390

    4. Nitric oxide enhances Th9 cell differentiation and airway inflammation.

      PubMed

      Niedbala, Wanda; Besnard, Anne-Gaelle; Nascimento, Daniele Carvalho; Donate, Paula Barbim; Sonego, Fabiane; Yip, Edwin; Guabiraba, Rodrigo; Chang, Hyun-Dong; Fukada, Sandra Y; Salmond, Robert J; Schmitt, Edgar; Bopp, Tobias; Ryffel, Bernhard; Liew, Foo Y

      2014-08-07

      Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumour suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(-/-) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared with wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells.

    5. The Combination of Early and Rapid Type I IFN, IL-1α, and IL-1β Production Are Essential Mediators of RNA-Like Adjuvant Driven CD4+ Th1 Responses

      PubMed Central

      Madera, Rachel F.; Wang, Jennifer P.; Libraty, Daniel H.

      2011-01-01

      There is a growing need for novel vaccine adjuvants that can provide safe and potent T-helper type 1 (Th1) activity. RNA-like immune response modifiers (IRMs) are candidate T-cell adjuvants that skew acquired immune responses towards a Th1 phenotype. We set out to delineate the essential signaling pathways by which the RNA-like IRMs, resiquimod (R-848) and polyinosinic:polycytidylic acid (poly I:C), augment CD4+ T-helper 1 (Th1) responses. Highly purified murine conventional dendritic cells (cDCs) and conventional CD4+ T-cells were co-cultured in allogeneic and MHC congenic mixed leukocyte reactions. The activation of CD4+ Th1 cells was examined utilizing cells from mice deficient in specific RNA-sensing pattern recognition receptors and signaling mediators. R-848 and poly I:C stimulation of Type I interferon production and signaling in cDCs was essential but not sufficient for driving CD4+ Th1 responses. The early and rapid production of IL-1α and IL-1β was equally critical for the optimal activation of Th1 CD4+ T-cells. R-848 activation of Toll-like receptor 7/MyD88-dependent signaling in cDCs led to a rapid upregulation of pro-IL-1α and pro-IL-1β production compared to poly I:C activation of MyD88-independent signaling pathways. The in vitro data show that CD4+ T-cell adjuvant activity of RNA-like IRMs is mediated by a critical combination of early and rapid Type I interferon, IL-1α and IL-1β production. These results provide important insights into the key signaling pathways responsible for RNA-like IRM CD4+ Th1 activation. A better understanding of the critical signaling pathways by which RNA-like IRMs stimulate CD4+ Th1 responses is relevant to the rational design of improved vaccine adjuvants. PMID:22206014

    6. 4th Rare Disease South Eastern Europe (See) Meeting Skopje, Macedonia (November 14th, 2015).

      PubMed

      Gucev, Zoran; Tasic, Velibor; Polenakovic, Momir

      2015-01-01

      The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on

    7. Comparison of Detection Limits of 4th Generation Combination HIV Antigen/Antibody, p24 Antigen and Viral Load Assays on Diverse HIV Isolates.

      PubMed

      Stone, Mars; Bainbridge, John; Sanchez, Ana M; Keating, Sheila M; Pappas, Andrea; Rountree, Wes; Todd, Chris; Bakkour, Sonia; Manak, Mark; Peel, Sheila A; Coombs, Robert W; Ramos, Eric M; Shriver, M Kathleen; Contestable, Paul; Nair, Sangeetha Vijaysri; Wilson, David H; Stengelin, Martin; Murphy, Gary; Hewlett, Indira; Denny, Thomas N; Busch, Michael P

      2018-05-23

      Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical 4 th generation antigen-antibody (Ag/Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab alone assays, but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening and next generation assays. Blinded 300 member panels of 20 serially diluted well-characterized antibody negative HIV isolates were distributed to manufacturers and end-user labs to assess relative analytic sensitivity of currently approved and pre-approved clinical HIV 4 th generation Ag/Ab combo or p24 Ag alone immunoassays across diverse subtypes. The limits of virus detection (LODs) were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blinded panel. Based on the proportion of positive results on 300 observations all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half log LODs, illustrating similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo-assays performed poorly. Similar performance of the different commercially available 4 th gen assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next generation pre-clinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while p24 Ag detection by rapid 4 th gen assays performed poorly. Copyright © 2018 American Society for Microbiology.

    8. Endotoxin Exposure during Sensitization to Blomia tropicalis Allergens Shifts TH2 Immunity Towards a TH17-Mediated Airway Neutrophilic Inflammation: Role of TLR4 and TLR2

      PubMed Central

      Barboza, Renato; Câmara, Niels Olsen Saraiva; Gomes, Eliane; Sá-Nunes, Anderson; Florsheim, Esther; Mirotti, Luciana; Labrada, Alexis; Alcântara-Neves, Neuza Maria; Russo, Momtchilo

      2013-01-01

      Experimental evidence and epidemiological studies indicate that exposure to endotoxin lipopolysaccharide (eLPS) or other TLR agonists prevent asthma. We have previously shown in the OVA-model of asthma that eLPS administration during alum-based allergen sensitization blocked the development of lung TH2 immune responses via MyD88 pathway and IL-12/IFN-γ axis. In the present work we determined the effect of eLPS exposure during sensitization to a natural airborne allergen extract derived from the house dust mite Blomia tropicalis (Bt). Mice were subcutaneously sensitized with Bt allergens co-adsorbed onto alum with or without eLPS and challenged twice intranasally with Bt. Cellular and molecular parameters of allergic lung inflammation were evaluated 24 h after the last Bt challenge. Exposure to eLPS but not to ultrapure LPS (upLPS) preparation during sensitization to Bt allergens decreased the influx of eosinophils and increased the influx of neutrophils to the airways. Inhibition of airway eosinophilia was not observed in IFN-γdeficient mice while airway neutrophilia was not observed in IL-17RA-deficient mice as well in mice lacking MyD88, CD14, TLR4 and, surprisingly, TLR2 molecules. Notably, exposure to a synthetic TLR2 agonist (PamCSK4) also induced airway neutrophilia that was dependent on TLR2 and TLR4 molecules. In the OVA model, exposure to eLPS or PamCSK4 suppressed OVA-induced airway inflammation. Our results suggest that B. tropicalis allergens engage TLR4 that potentiates TLR2 signaling. This dual TLR activation during sensitization results in airway neutrophilic inflammation associated with increased frequency of lung TH17 cells. Our work highlight the complex interplay between bacterial products, house dust mite allergens and TLR signaling in the induction of different phenotypes of airway inflammation. PMID:23805294

    9. Comparison between Hardy-Rand-Rittler 4th edition and Ishihara color plate tests for detection of dyschromatopsia in optic neuropathy.

      PubMed

      Huna-Baron, Ruth; Glovinsky, Yoseph; Habot-Wilner, Zohar

      2013-02-01

      The aim of this work was to compare the specificity-sensitivity balance of the Hardy-Rand-Rittler (HRR) 4th edition with the Ishihara color plate tests for color-vision defects in patients with optic neuropathy. This is a prospective case-control study. The study group included 43 patients (48 eyes) with newly diagnosed optic neuropathy, and the control group included 33 patients (33 right eyes) who were referred to the eye clinic for conditions other than optic nerve or retinal macular disorders. Individuals with visual acuity of less than 20/70 (0.54 Log MAR) were excluded. All patients underwent comprehensive eye examination and color-vision evaluation with both tests in a random order under standardized lighting conditions. The scores of the Ishihara and HRR tests were set as the number of plates identified out of 12 and six respectively. The receiver operating characteristics (ROC) curve was statistically significantly better when using the HRR test (area under curve [AUC] = 0.93 ± 0.03) than for the Ishihara test (AUC = 0.77 ± 0.05) (P = 0.0006). The best specificity-sensitivity balance for the HRR was 100 % and 79 % respectively, and for the Ishihara test 100 % and 48 % respectively. The HRR 4th edition test proved to be superior to the Ishihara test in detecting acquired dyschromatopsia due to optic neuropathy. We recommend using the HRR 4th edition test as a screening method for detection of color-vision defects in patients with optic neuropathy.

    10. Proceedings of the International Conference on Educational Data Mining (EDM) (4th, Eindhoven, the Netherlands, July 6-8, 2011)

      ERIC Educational Resources Information Center

      Pechenizkiy, Mykola; Calders, Toon; Conati, Cristina; Ventura, Sebastian; Romero, Cristobal; Stamper, John

      2011-01-01

      The 4th International Conference on Educational Data Mining (EDM 2011) brings together researchers from computer science, education, psychology, psychometrics, and statistics to analyze large datasets to answer educational research questions. The conference, held in Eindhoven, The Netherlands, July 6-9, 2011, follows the three previous editions…

    11. Oridonin's therapeutic effect: suppressing Th1/Th17 simultaneously in a mouse model of Crohn's disease.

      PubMed

      Wang, Shubei; Zhang, Yong; Saas, Philippe; Wang, Haili; Xu, Ying; Chen, Ke; Zhong, Jie; Yuan, Yaozong; Wang, Ying; Sun, Yunwei

      2015-03-01

      Crohn's disease is a chronic inflammatory bowel disease. Oridonin is an effective component isolated from Rabdosia rubescens. It can inhibit the activation of transcription factor nuclear factor-kappa B and suppress the over expression of cytokines. We postulated that oridonin may be a potential therapeutic candidate for Crohn's disease. To confirm the postulation, we investigated clinical and immunologic modulations of oridonin in a mouse model of trinitrobenzene sulfonic acid-induced colitis. It was found that oridonin attenuated trinitrobenzene sulfonic acid-induced colitis as represented by a reduction in colonic interferon-γ/inteleukin-17 secretion and a decrement in splenic Th1/Th17 cells and effector memory CD4(+) T cells. Oridonin treatment inhibited the proliferation of CD4(+) T cells and upregulated the apoptosis of lymphocytes by inhibiting nuclear translocation of transcription factor nuclear factor-kappa B. Oridonin is a potential modulator for trinitrobenzene sulfonic acid-induced colitis and other Th1/Th17 mediated inflammatory diseases. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

    12. Modelling of Technological Solutions to 4th Generation DH Systems

      NASA Astrophysics Data System (ADS)

      Vigants, Edgars; Prodanuks, Toms; Vigants, Girts; Veidenbergs, Ivars; Blumberga, Dagnija

      2017-11-01

      Flue gas evaporation and condensing processes are investigated in a direct contact heat exchanger - condensing unit, which is installed after a furnace. By using equations describing processes of heat and mass transfer, as well as correlation coherences for determining wet gas parameters, a model is formed to create a no-filling, direct contact heat exchanger. Results of heating equipment modelling and experimental research on the gas condensing unit show, that the capacity of the heat exchanger increases, when return temperature of the district heating network decreases. In order to explain these alterations in capacity, the character of the changes in water vapour partial pressure, in the propelling force of mass transfer, in gas and water temperatures and in the determining parameters of heat transfer are used in this article. The positive impact on the direct contact heat exchanger by the decreased district heating (DH) network return temperature shows that introduction of the 4th generation DH system increases the energy efficiency of the heat exchanger. In order to make an assessment, the methodology suggested in the paper can be used in each particular situation.

    13. Assessing physical activity in adolescents: common activities of children in 6th-8th grades.

      PubMed

      Harrell, Joanne S; Pearce, Patricia F; Markland, Ella Trivett; Wilson, Kristina; Bradley, Chyrise B; McMurray, Robert G

      2003-04-01

      To provide data for physical activity assessment in practice by describing the leisure time activities of adolescents and determining if the activities and the metabolic equivalents (MET levels) of those activities differ for boys and girls. The study was conducted in five middle schools in three rural counties in North Carolina. Subjects were 1,211 6th, 7th, and 8th graders aged 11-14 (mean 12.2) years. Half (52.5%) were girls. The sample was 64% white, 24% African-American and 12% other races. The top five activities of boys were football, basketball, bicycling, running, and baseball; the top five activities of girls were talking, running, walking, bicycling, and dancing. The average MET was 5.3 for boys and 4.3 for girls (p = 0.000). By grade levels, 6th graders had an average MET of 4.9 and the MET of 8th graders was 4.5 (p < 0.05). Older youth, girls, and children of parents with more education reported significantly more sedentary activities than the other youth. Physical activity is an integral component of overall health. Once activities and activity levels are known, current practices can be augmented or changed to accommodate improved understanding of physical activity. Because an active lifestyle is important in preventing obesity and other chronic conditions and for general health, nurse practitioners (NPs) should ask adolescents about their common activities and encourage them to continue the more vigorous activities and reduce time spent in sedentary pursuits. Prescriptive physical activity can be included for primary, secondary, or even tertiary prevention, thus crossing all levels of NP practice.

    14. A Novel Epitope from CD22 Regulates Th1 and Th17 Cell Function in Systemic Lupus Erythematosus

      PubMed Central

      Chen, Xiao; Zhang, Li-Hua; Song, You; Cheng, Xiang; Zhou, Zi-Hua; Wang, Min; Guo, He-Ping; Du, Rong; Liao, Yu-Hua

      2013-01-01

      The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4+ T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4+ T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4+ T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4+ T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4+ T cells. Moreover, the expression of CD45RO on CD4+ T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases. PMID:23704998

    15. A novel epitope from CD22 regulates Th1 and Th17 cell function in systemic lupus erythematosus.

      PubMed

      Yuan, Jing; Yu, Miao; Cao, Ai-Lin; Chen, Xiao; Zhang, Li-Hua; Song, You; Cheng, Xiang; Zhou, Zi-Hua; Wang, Min; Guo, He-Ping; Du, Rong; Liao, Yu-Hua

      2013-01-01

      The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4(+) T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4(+) T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4(+) T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4(+) T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4(+) T cells. Moreover, the expression of CD45RO on CD4(+) T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.

    16. Stable T-bet(+)GATA-3(+) Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation.

      PubMed

      Peine, Michael; Rausch, Sebastian; Helmstetter, Caroline; Fröhlich, Anja; Hegazy, Ahmed N; Kühl, Anja A; Grevelding, Christoph G; Höfer, Thomas; Hartmann, Susanne; Löhning, Max

      2013-01-01

      Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN)-γ and interleukin (IL)-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet(+)GATA-3(+) cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation.

    17. Reforming the 4th-Year Curriculum as a Springboard to Graduate Medical Training: One School's Experiences and Lessons Learned.

      PubMed

      Wackett, Andrew; Daroowalla, Feroza; Lu, Wei-Hsin; Chandran, Latha

      2016-01-01

      Concerns regarding the quality of training in the 4th year of medical school and preparation of graduates to enter residency education persist and are borne out in the literature. We reviewed the published literature regarding Year 4 concerns as well as institutional efforts to improve the 4th-year curriculum from several schools. Based on input from key stakeholders, we established 4 goals for our Year 4 curriculum reform: (a) standardize the curricular structure, (b) allow flexibility and individualization, (c) improve the preparation for residency, and (d) improve student satisfaction. After the reform, we evaluated the outcomes using results from the Association of American Medical Colleges Questionnaire, student focus groups, and program director surveys. This article describes the context, process, and outcomes of the reform of the Year 4 curriculum at Stony Brook University School of Medicine. We were able to achieve all four stated goals for the reform. The significant components of the change included a flexible adaptable curriculum based on individual needs and preferences, standardized learning objectives across the year, standardized competency-based evaluations regardless of discipline, reinforcement of clinical skills, and training for the transition to the workplace as an intern. The reform resulted in increased student satisfaction, increased elective time, and increased preparedness for residency training as perceived by the graduates. The Program Director survey showed significant changes in ability to perform a medical history and exam, management of common medical conditions and emergencies, clinical reasoning and problem-solving skills, working and communication with the healthcare team, and overall professionalism in meeting obligations inherent in the practice of medicine. Lessons learned from our 4th-year reform process are discussed. Listening to the needs of the stakeholders was an important step in ensuring buy-in, having an institutional

    18. 4th Annual SATN Conference 2011: Curriculum Transformation at Universities of Technology: Towards Development of New Generation Universities

      ERIC Educational Resources Information Center

      Mthembu, T.

      2012-01-01

      The South African Technology Network (SATN) would like to thank the Editor of the "South African Journal of Higher Education" (SAJHE) for the opportunity to publish papers read at the 4th Annual SATN Conference that was hosted by Central University of Technology and held in Bloemfontein in November 2011. The journal makes it possible for…

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

      PubMed Central

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

      2015-01-01

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

    20. Energetics of a uranothorite (Th 1–xU xSiO 4) solid solution

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Guo, Xiaofeng; Szenknect, Stephanie; Mesbah, Adel

      High-temperature oxide melt solution calorimetric measurements were completed to determine the enthalpies of formation of the uranothorite, (USiO 4) x–(ThSiO 4) 1–x, solid solution. Phase-pure samples with x values of 0, 0.11, 0.21, 0.35, 0.71, and 0.84 were prepared, purified, and characterized by powder X-ray diffraction, electron probe microanalysis, thermogravimetric analysis and differential scanning calorimetry coupled with in situ mass spectrometry, and high-temperature oxide melt solution calorimetry. This work confirms the energetic metastability of coffinite, USiO 4, and U-rich intermediate silicate phases with respect to a mixture of binary oxides. Furthermore, variations in unit cell parameters and negative excess volumesmore » of mixing, coupled with strongly exothermic enthalpies of mixing in the solid solution, suggest short-range cation ordering that can stabilize intermediate compositions, especially near x = 0.5.« less

    1. Energetics of a uranothorite (Th 1–xU xSiO 4) solid solution

      DOE PAGES

      Guo, Xiaofeng; Szenknect, Stephanie; Mesbah, Adel; ...

      2016-10-11

      High-temperature oxide melt solution calorimetric measurements were completed to determine the enthalpies of formation of the uranothorite, (USiO 4) x–(ThSiO 4) 1–x, solid solution. Phase-pure samples with x values of 0, 0.11, 0.21, 0.35, 0.71, and 0.84 were prepared, purified, and characterized by powder X-ray diffraction, electron probe microanalysis, thermogravimetric analysis and differential scanning calorimetry coupled with in situ mass spectrometry, and high-temperature oxide melt solution calorimetry. This work confirms the energetic metastability of coffinite, USiO 4, and U-rich intermediate silicate phases with respect to a mixture of binary oxides. Furthermore, variations in unit cell parameters and negative excess volumesmore » of mixing, coupled with strongly exothermic enthalpies of mixing in the solid solution, suggest short-range cation ordering that can stabilize intermediate compositions, especially near x = 0.5.« less

    2. Combined crystal chemistry and DFT studies of ThNCl and Th2N2X (X: chalcogen) behaving as pseudo-binaries

      NASA Astrophysics Data System (ADS)

      Matar, Samir F.; Kfoury, Charbel N.

      2018-02-01

      Common features and peculiar differentiations characterize binary and ternary thorium nitride Th3N4, thorium nitride chloride ThNCl and the family of thorium nitride chalcogenides Th2N2X (X = O, S, Se, Te) investigated in the framework of the quantum density functional theory DFT. Particularly the dominant effect of the Th-N covalent bond stronger than ionic Th-Cl/Th-X ones as identified from analyses of bonding from overlap integral, electron localization function mapping, electronic density of states and charge transfer, is found at the origin of the layered-like structural arrangements in Th-N monolayers within ThNCl (Cl / [ThN]/ Cl) and Th-N double layers in Th2N2X (X / [Th2N2] / X) with the result of pseudo binary compounds: [ThN]+Cl- and [Th2N2] 2+X2-. All compounds are found semi-conducting with ∼2 eV band gap. It is claimed that such insights into Solid State Chemistry can help rationalizing complex compounds more comprehensively (two examples given).

    3. Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

      PubMed

      Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

      2014-04-15

      Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

    4. Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children.

      PubMed

      Jenmalm, M C; Van Snick, J; Cormont, F; Salman, B

      2001-10-01

      Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma in the cell supernatants were analysed by ELISA. Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.

    5. Dendritic cell MST1 inhibits Th17 differentiation

      PubMed Central

      Li, Chunxiao; Bi, Yujing; Li, Yan; Yang, Hui; Yu, Qing; Wang, Jian; Wang, Yu; Su, Huilin; Jia, Anna; Hu, Ying; Han, Linian; Zhang, Jiangyuan; Li, Simin; Tao, Wufan; Liu, Guangwei

      2017-01-01

      Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. PMID:28145433

    6. Teacher Implementation of Reform-Based Mathematics and Implications for Algebra Readiness: A Qualitative Study of 4th Grade Classrooms

      ERIC Educational Resources Information Center

      Sher, Stephen Korb

      2011-01-01

      This study looked at 4th grade classrooms to see "how" teachers implement NCTM standards-based or reform-based mathematics instruction and then analyzed it for the capacity to improve students' "algebra readiness." The qualitative study was based on classroom observations, teacher and administrator interviews, and teacher surveys. The study took…

    7. Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

      PubMed Central

      Li, Jianchao; He, Yunyun; Weck, Meredith L.; Lu, Qing; Tyska, Matthew J.; Zhang, Mingjie

      2017-01-01

      Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a. PMID:28439001

    8. Reciprocal modulation of helper Th1 and Th17 cells by the β2-adrenergic receptor agonist drug terbutaline.

      PubMed

      Carvajal Gonczi, Catalina M; Tabatabaei Shafiei, Mahdieh; East, Ashley; Martire, Erika; Maurice-Ventouris, Meagane H I; Darlington, Peter J

      2017-09-01

      Catecholamine hormones are powerful regulators of the immune system produced by the sympathetic nervous system (SNS). They regulate the adaptive immune system by altering T-cell differentiation into T helper (Th) 1 and Th2 cell subsets, but the effect on Th17 cells is not known. Th17 cells, defined, in part, by chemokine receptor CCR6 and cytokine interleukin (IL)-17A, are crucial for mediating certain pathogen-specific responses and are linked with several autoimmune diseases. We demonstrated that a proportion of human Th17 cells express beta 2-adrenergic receptor (β2AR), a G protein-coupled receptor that responds to catecholamines. Activation of peripheral blood mononuclear cells, which were obtained from venous blood drawn from healthy volunteers, with anti-cluster of differentiation 3 (CD3) and anti-CD28 and with a β2-agonist drug, terbutaline (TERB), augmented IL-17A levels (P < 0.01) in the majority of samples. TERB reduced interferon gamma (IFNγ) indicating that IL-17A and IFNγ are reciprocally regulated. Similar reciprocal regulation was observed with dbcAMP. Proliferation of Th cells was monitored by carboxyfluorescein diacetate N-succinimidyl ester labeling and flow cytometry with antibody staining for CD3 and CD4. TERB increased proliferation by a small but significant margin (P < 0.001). Next, Th17 cells (CD4 + CXCR3 - CCR6 + ) were purified using an immunomagnetic positive selection kit, which removes all other mononuclear cells. TERB increased IL-17A from purified Th17 cells, which argues that TERB acts directly on Th17 cells. Thus, hormone signals from the SNS maintain a balance of Th cells subtypes through the β2AR. © 2017 Federation of European Biochemical Societies.

    9. Effectiveness of ivermectin against later 4th-stage Strongylus vulgaris in ponies.

      PubMed

      Slocombe, J O; McCraw, B M; Pennock, P W; Vasey, J

      1982-09-01

      Twelve pony foals were reared worm-free and inoculated with Strongylus vulgaris. Approximately 8 weeks after they were inoculated, 6 foals were given ivermectin IM at a dosage rate of 200 micrograms/kg of body weight and 6 were given a placebo. All foals were necropsied 35 days after treatment. Ivermectin was 98.9% effective in eliminating later 4th-stage S vulgaris larvae located near the origin of major intestinal arteries and in reducing clinical signs and permitting resolution of lesions associated with verminous arteritis. One pony foal reared on pasture and with evidence of arteritis of the cranial mesenteric and ileocolic arteries on arteriography was treated with ivermectin at a dosage rate of 200 micrograms/kg of body weight. On arteriographs taken subsequently, there was evidence of regression of the lesion, and at necropsy 9 weeks after treatment, there was no arteritis or larvae in those arteries.

    10. Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris.

      PubMed

      Timoteo, Rodolfo Pessato; da Silva, Marcos Vinicius; Miguel, Camila Botelho; Silva, Djalma Alexandre Alves; Catarino, Jonatas Da Silva; Rodrigues Junior, Virmondes; Sales-Campos, Helioswilton; Freire Oliveira, Carlo Jose

      2017-01-01

      Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN- γ , IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF- α , IL-1 β , IL-4, IL-9, IL-12, TGF- β , IL-33, MCP-1, RANTES, and MIP-1 α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.

    11. The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance.

      PubMed

      Fujiwara, Daisuke; Inoue, Sayo; Wakabayashi, Hideyuki; Fujii, Toshio

      2004-11-01

      There is growing interest in the immune-stimulating effect and in particular, the anti-allergic effect, of lactic acid bacteria (LAB). However, no comprehensive studies have been done that compare the immune-stimulating potential of LAB strains. The in vitro immune-stimulating effects on Th1/Th2 balance of more than 100 LAB strains were compared in splenocytes from ovalbumin-sensitized Th2-polarized mice. The in vivo anti-allergic ability of strain KW3110 was studied in the Th2-polarized model by detecting serum IgE concentration, Th1/Th2 cytokine secretion from splenocytes, and the expression of co-stimulatory molecules on macrophages. In vitro studies from Th2-polarized splenocytes, using IL-12 as a Th1 parameter and IL-4 secretion as a Th2 parameter revealed a wide variety of IL-12-inducing and IL-4-repressing activities, depending on the strain of LAB, not depending on the species. However, evaluation of individual strains in vivo revealed that after exposure to Lactobacillus paracasei KW3110 strain, the serum IgE elevation elicited by repeated OVA injection of mice was strongly inhibited. Cytokine secretion from splenocytes 20 weeks after KW3110 administration showed increased IL-12 and decreased IL-4 expression. Both CD40 and B7-1 expression on macrophages was upregulated by administration of KW3110. Improving the consequences of the Th1/Th2 imbalance by administration of LAB was dependent upon the LAB strain rather than the LAB species. Oral KW3110 administration in the mouse allergy model directed the Th1/Th2 balance toward Th1 through the maturation of APCs and inhibition of serum IgE elevation.

    12. Decreased frequency of peripheral CD4(+) CD161(+) Th(17) -precursor cells in kidney transplant recipients on long-term therapy with Belatacept.

      PubMed

      Vondran, Florian Wolfgang Rudolf; Timrott, Kai; Kollrich, Sonja; Klempnauer, Juergen; Schwinzer, Reinhard; Becker, Thomas

      2012-04-01

      Clinical trials have pointed out the promising role of co-stimulation blocker Belatacept for improvement of graft function and avoidance of undesired side-effects associated with calcineurin-inhibitors (CNI). However, due to the worldwide limited availability of appropriate patients, almost no data exist to assess the effects of sustained application of this immunomodulator on the recipient's immune system. The aim of this study was to reveal specific alterations in the composition of immunologic subpopulations potentially involved in development of tolerance or chronic graft rejection following long-term Belatacept therapy. For this, peripheral lymphocyte subsets of kidney recipients treated with Belatacept (n=5; average 7.8years) were determined by flow-cytometry and compared with cells from matched patients on CNI (n=9) and healthy controls (n=10). T cells capable of producing IL-17 and serum levels of soluble CD30 were quantified. Patients on CNI showed a higher frequency of CD4(+) CD161(+) Th(17) -precursors and IL-17-producing CD4(+) T cells than Belatacept patients and controls. Significantly higher serum levels of soluble CD30 were observed in CNI patients, indicating a possible involvement of the CD30/CD30L-system in Th(17) -differentiation. No differences were found concerning CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells. In conclusion, patients on therapy with Belatacept did not show a comparable Th(17) -profile to that seen in individuals with chronic intake of CNI. The distinct effects of Belatacept on Th(17) -immunity might prove beneficial for the long-term outcome following kidney transplantation. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

    13. European Code against Cancer 4th Edition: Alcohol drinking and cancer.

      PubMed

      Scoccianti, Chiara; Cecchini, Michele; Anderson, Annie S; Berrino, Franco; Boutron-Ruault, Marie-Christine; Espina, Carolina; Key, Timothy J; Leitzmann, Michael; Norat, Teresa; Powers, Hilary; Wiseman, Martin; Romieu, Isabelle

      2016-12-01

      Alcohol consumption is the third leading risk factor for disease and mortality in Europe. As evaluated by the International Agency for Research on Cancer (IARC) Monographs, a causal relationship is established for consumption of alcoholic beverages and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum and female breast, even at low and moderate alcohol intakes. The higher the amount of alcohol consumed, the higher the risk of developing cancer. In Europe, an estimated 10% (95% CI: 7%-13%) of all cancer cases in men and 3% (95% CI: 1%-5%) of all cancer cases in women are attributable to alcohol consumption. Several biological mechanisms explain the carcinogenicity of alcohol; among them, ethanol and its genotoxic metabolite, acetaldehyde, play a major role. Taking all this evidence into account, a recommendation of the 4th edition of European Code against Cancer is: "If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention." Copyright © 2016 International Agency for Research on Cancer. Published by Elsevier Ltd.. All rights reserved.

    14. Analysis of Lexical Quality and Its Relation to Writing Quality for 4th Grade, Primary School Students in Chile

      ERIC Educational Resources Information Center

      Gómez Vera, Gabriela; Sotomayor, Carmen; Bedwell, Percy; Domínguez, Ana María; Jéldrez, Elvira

      2016-01-01

      Few studies have addressed vocabulary quality in developing writing skill in Spanish. Even less addressed it within the Chilean educational system. The specific objective of this study was to characterize, using a comprehensive set of indicators, the quality of the vocabulary produced by Chilean 4th grade students. Based on a national writing…

    15. Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst burden of neurocysticercosis.

      PubMed

      Tharmalingam, J; Prabhakar, A T; Gangadaran, P; Dorny, P; Vercruysse, J; Geldhof, P; Rajshekhar, V; Alexander, M; Oommen, A

      2016-10-01

      Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an important cause of acquired seizures in endemic countries, which relate to number, location and degenerating cysts in the brain. Multicyst infections are common in endemic countries although single-cyst infection prevails in India. Single-cyst infections in an endemic country suggest a role for host immunity limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood mononuclear cells of healthy subjects from endemic and nonendemic regions and of single- and multicyst-infected patients for association with cyst burden of NCC. T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of T. solium-endemic and T. solium-non-endemic regions and those with single-cyst infections and a Th2 cytokine response from subjects with multicyst neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines and low effector T cells may enable multiple-cyst infections to establish and persist. © 2016 John Wiley & Sons Ltd.

    16. Quality of Education Predicts Performance on the Wide Range Achievement Test-4th Edition Word Reading Subtest

      PubMed Central

      Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.; Dean, Andy C.; Thames, April D.

      2014-01-01

      The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature. PMID:25404004

    17. Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation

      PubMed Central

      Wright, Paulette L.; Yu, Jun; Di, Y.P. Peter; Homer, Robert J.; Chupp, Geoffrey; Elias, Jack A.; Cohn, Lauren

      2010-01-01

      Nogo-B is a member of the reticulon family of proteins (RTN-4B) that is highly expressed in lung tissue; however, its function remains unknown. We show that mice with Th2-driven lung inflammation results in a loss of Nogo expression in airway epithelium and smooth muscle compared with nonallergic mice, a finding which is replicated in severe human asthma. Mice lacking Nogo-A/B (Nogo-KO) display an exaggerated asthma-like phenotype, and epithelial reconstitution of Nogo-B in transgenic mice blunts Th2-mediated lung inflammation. Microarray analysis of lungs from Nogo-KO mice reveals a marked reduction in palate lung and nasal clone (PLUNC) gene expression, and the levels of PLUNC are enhanced in epithelial Nogo-B transgenic mice. Finally, transgenic expression of PLUNC into Nogo-KO mice rescues the enhanced asthmatic-like responsiveness in these KO mice. These data identify Nogo-B as a novel protective gene expressed in lung epithelia, and its expression regulates the levels of the antibacterial antiinflammatory protein PLUNC. PMID:20975041

    18. Cell Surface Galectin-9 Expressing Th Cells Regulate Th17 and Foxp3+ Treg Development by Galectin-9 Secretion

      PubMed Central

      Niki, Toshiro; Kadowaki, Takeshi; Ueno, Masaki; Nishi, Nozomu; Yamauchi, Akira; Hattori, Toshio; Masaki, Tsutomu; Hirashima, Mitsuomi

      2012-01-01

      Galectin-9 (Gal-9), a β-galactoside binding mammalian lectin, regulates immune responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and increasing anti-inflammatory Foxp3+ regulatory T cells (Treg) in vitro and in vivo. These functions of Gal-9 are thought to be exerted by binding to receptor molecules on the cell surface. However, Gal-9 lacks a signal peptide for secretion and is predominantly located in the cytoplasm, which raises questions regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have been elusive. We report here that CD4 T cells expressing Gal-9 on the cell surface (Gal-9+ Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation, but other CD4 T cells do not, although they express an equivalent amount of intracellular Gal-9. Gal-9+ Th cells expressed interleukin (IL)-10 and transforming growth factor (TGF)-β but did not express Foxp3. In a co-culture experiment, Gal-9+ Th cells regulated Th17/Treg development in a manner similar to that by exogenous Gal-9, during which the regulation by Gal-9+ Th cells was shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-β blockades. Further elucidation of Gal-9+ Th cells in humans indicates a conserved role of these cells through evolution and implies the possible utility of these cells for diagnosis or treatment of immunological diseases. PMID:23144904

    19. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

      PubMed

      Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

      2015-12-01

      The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events. Copyright © 2015 International

    20. CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis.

      PubMed

      Paulissen, Sandra M J; van Hamburg, Jan Piet; Davelaar, Nadine; Vroman, Heleen; Hazes, Johanna M W; de Jong, Pascal H P; Lubberts, Erik

      2015-11-30

      Patients with rheumatoid arthritis (RA) can be separated into two major subpopulations based on the absence or presence of serum anti-citrullinated protein antibodies (ACPAs). The more severe disease course in ACPA(+) RA and differences in treatment outcome between these subpopulations suggest that ACPA(+) and ACPA(-) RA are different disease subsets. The identification of T-helper (Th) cells specifically recognizing citrullinated peptides, combined with the strong association between HLA-DRB1 and ACPA positivity, point toward a pathogenic role of Th cells in ACPA(+) RA. In this context we recently identified a potential pathogenic role for CCR6(+) Th cells in RA. Therefore, we examined whether Th cell population distributions differ by ACPA status. We performed a nested matched case-control study including 27 ACPA(+) and 27 ACPA(-) treatment-naive early RA patients matched for disease activity score in 44 joints, presence of rheumatoid factor, sex, age, duration of complaints and presence of erosions. CD4(+)CD45RO(+) (memory) Th cell distribution profiles from these patients were generated based on differential chemokine receptor expression and related with disease duration. ACPA status was not related to differences in total CD4(+) T cell or memory Th cell proportions. However, ACPA(+) patients had significantly higher proportions of Th cells expressing the chemokine receptors CCR6 and CXCR3. Similar proportions of CCR4(+) and CCR10(+) Th cells were found. Within the CCR6(+) cell population, four Th subpopulations were distinguished based on differential chemokine receptor expression: Th17 (CCR4(+)CCR10(-)), Th17.1 (CXCR3(+)), Th22 (CCR4(+)CCR10(+)) and CCR4/CXCR3 double-positive (DP) cells. In particular, higher proportions of Th22 (p = 0.02), Th17.1 (p = 0.03) and CCR4/CXCR3 DP (p = 0.01) cells were present in ACPA(+) patients. In contrast, ACPA status was not associated with differences in Th1 (CCR6(-)CXCR3(+); p = 0.90), Th2 (CCR6(-)CCR4(+); p = 0.27) and T

    1. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, Volume 2

      NASA Technical Reports Server (NTRS)

      Krishen, Kumar (Editor); Burnham, Calvin (Editor)

      1995-01-01

      This document contains papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held June 27-July 1, 1994 in Orlando, Florida. These documents encompass research, technology, applications, funding, political, and social aspects of superconductivity. The areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges; and power and energy applications.

    2. The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy.

      PubMed

      Bacharova, Ljuba; Estes, Harvey E; Schocken, Douglas D; Ugander, Martin; Soliman, Elsayed Z; Hill, Joseph A; Bang, Lia E; Schlegel, Todd T

      The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed. Copyright © 2016 Elsevier Inc. All rights reserved.

    3. Invariant NKT cells inhibit development of the Th17 lineage

      PubMed Central

      Mars, Lennart T.; Araujo, Luiza; Kerschen, Philippe; Diem, Séverine; Bourgeois, Elvire; Van, Linh Pham; Carrié, Nadège; Dy, Michel; Liblau, Roland S.; Herbelin, André

      2009-01-01

      T cells differentiate into functionally distinct effector subsets in response to pathogen encounter. Cells of the innate immune system direct this process; CD1d-restricted invariant natural killer T (iNKT) cells, for example, can either promote or inhibit Th1 and Th2 responses. Recently, a new subset of CD4+ T helper cells, called Th17, was identified that is implicated in mucosal immunity and autoimmune disorders. To investigate the influence of iNKT cells on the differentiation of naïve T cells we used an adoptive transfer model of traceable antigen-specific CD4+ T cells. Transferred naïve CD25−CD62L+ CD4+ T cells were primed by antigen immunization of the recipient mice, permitting their expansion and Th17 differentiation. This study establishes that in vivo activation of iNKT cells during T-cell priming impedes the commitment of naïve T cells to the Th17 lineage. In vivo cytokine neutralization experiments revealed a role for IL-4, IL-10, and IFN-γ in the iNKT-cell-mediated regulation of T-cell lineage development. Moreover, by comparing IL-17 production by antigen-experienced T cells from unmanipulated wild-type mice and iNKT-cell-deficient mice, we demonstrate an enhanced Th17 response in mice lacking iNKT cells. This invigorated Th17 response reverts to physiological levels when iNKT cells are introduced into Jα18−/− mice by adoptive transfer, indicating that iNKT cells control the Th17 compartment at steady state. We conclude that iNKT cells play an important role in limiting development of the Th17 lineage and suggest that iNKT cells provide a natural barrier against Th17 responses. PMID:19325124

    4. The transcription factor Th-POK negatively regulates Th17 differentiation in Vα14i NKT cells

      PubMed Central

      Engel, Isaac; Zhao, Meng; Kappes, Dietmar; Taniuchi, Ichiro

      2012-01-01

      The majority of mouse Vα14 invariant natural killer T (Vα14i NKT) cells produce several cytokines, including IFNγ and IL-4, very rapidly after activation. A subset of these cells, known as NKT17 cells, however, differentiates in the thymus to preferentially produce IL-17. Here, we show that the transcription factor—known as T helper, Poxviruses, and Zinc-finger and Krüppel family, (Th-POK)—represses the formation of NKT17 cells. Vα14i NKT cells from Th-POK–mutant helper deficient (hd/hd) mice have increased transcripts of genes normally expressed by Th17 and NKT17 cells, and even heterozygosity for this mutation leads to dramatically increased numbers of Vα14i NKT cells that are poised to express IL-17, especially in the thymus and lymph nodes. In addition, using gene reporter mice, we demonstrate that NKT17 cells from wild-type mice express lower amounts of Th-POK than the majority population of Vα14i NKT cells. We also show that retroviral transduction of Th-POK represses the expression of the Th17 master regulator RORγT in Vα14i NKT-cell lines. Our data suggest that NKT17-cell differentiation is intrinsically regulated by Th-POK activity, with only low levels of Th-POK permissive for the differentiation of NKT17 cells. PMID:23034280

    5. Defective GATA-3 expression in Th2 LCR-deficient mice.

      PubMed

      Hwang, Soo Seok; Kim, Kiwan; Lee, Gap Ryol

      2011-07-15

      Th2 cell differentiation is critically influenced by transcription factor GATA-3 and by various cis-acting elements including enhancers, silencers and a locus control region (LCR) in the Th2 cytokine locus. Th2 LCR-deficient Th2 cells completely lost the expression of GATA-3 and the phosphorylation of STAT6. Histone 3 lysine 4 (H3-K4) was hypomethylated in the gata3 locus in these cells. GATA-3 and STAT6 bound several regulatory regions in the gata3 locus and transactivated the expression of the gata3 gene. These results suggest that Th2 differentiation program stimulates feed-forward regulation of gata3 gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

    6. [Discussion on several contents of textbook Acupuncture and Moxibustion (New Century 4th Edition)].

      PubMed

      Tian, Kaiyu

      2018-02-12

      The textbook Acupuncture and Moxibustion (New Century 4th Edition) was published by China Press of Traditional Chinese Medicine in August of 2016. The author proposed several discussions in the textbook. The information, including the issue date of China national standard Standardized Manipulations of Acupuncture and Moxibustion , the number of foreign countries where China medical teams were assigned, and the number of acupuncture indications recommended by WHO, was not accurate. The content, including several methods of acupoint location, specification of filiform needles, rotating angle of needle, disinfection of needles and skin, locations and indications of scalp acupuncture, etc. should be corrected. Besides, the writing of textbooks should follow national or industry standards.

    7. Transcriptional Regulation of Th17 Cell Differentiation

      PubMed Central

      Ivanov, Ivaylo I.; Zhou, Liang; Littman, Dan R.

      2009-01-01

      The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been profoundly shaken by the discovery of T cells that secrete IL-17 and other inflammatory cytokines. This subset, referred to as Th17, is centrally involved in autoimmune disease and is important in host defense at mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23, and TGF-β, function sequentially or synergistically to induce the Th17 lineage. Other cytokines, including IL-2, IL-4, IFNγ, and IL-27, inhibit differentiation of this lineage. Here we review how the nuclear orphan receptor RORγt functions to coordinate the diverse cytokine-induced signals and thus control Th17 cell differentiation. PMID:18053739

    8. 75th Ranger Regiment Nutrition Program

      DTIC Science & Technology

      2008-07-15

      75th Ranger Regiment Nutrition Program LTC Russ Kotwal CPT Nick Barringer Medical Director Dietician SFC Cesar Veliz SFC Justin...Siple Medical Training Culinary Advisor Warfighter Nutrition Conference USUHS, Bethesda, MD 15 JULY 2008 Report Documentation Page Form...DATES COVERED - 4. TITLE AND SUBTITLE 75th Ranger Regiment Nutrition Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

    9. Psychological operations supporting counterinsurgency: 4th Psyop Group in Vietnam.

      DTIC Science & Technology

      2007-06-15

      LTC Karl D . Zetmeir, MS. Accepted this 15th day of June 2007 by: , Director, Graduate Degree Programs Robert F. Baumann, Ph.D...APPENDIX C. PSYOP TASK ORGANIZATION.........................................................108 APPENDIX D . MAP OF PSYOP UNIT LOCATIONS...while Sandler’s is a more general long-term history of military PSYOP. Lieutenant Colonel Harry D . Latimer’s U.S. Psychological Operations in

    10. R&W Club Frederick Hosts 4th Annual Golf Tournament Benefiting The Children’s Inn at NIH | Poster

      Cancer.gov

      The R&W Club Frederick’s 4th Annual Golf Tournament to benefit the Children’s Inn at NIH teed off on time despite cloudy weather and scattered showers. Employees from NCI at Frederick, the main NIH campus, and Leidos Biomed, along with family and friends, came to enjoy an afternoon at the beautiful Maryland National Golf Club in Middletown and to support a wonderful charity.

    11. Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris

      PubMed Central

      Timoteo, Rodolfo Pessato; Silva, Djalma Alexandre Alves; Catarino, Jonatas Da Silva; Rodrigues Junior, Virmondes

      2017-01-01

      Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1β, IL-4, IL-9, IL-12, TGF-β, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins. PMID:28321152

    12. Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway

      PubMed Central

      Anipindi, Varun C.; Dizzell, Sara E.; Nguyen, Philip V.; Shaler, Christopher R.; Chu, Derek K.; Jiménez-Saiz, Rodrigo; Liang, Hong; Swift, Stephanie; Nazli, Aisha; Kafka, Jessica K.; Bramson, Jonathan; Xing, Zhou; Jordana, Manel; Wan, Yonghong; Snider, Denis P.; Stampfli, Martin R.; Kaushic, Charu

      2016-01-01

      Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV and other sexually transmitted infections. Here, we investigated the underlying mechanism. Better protection in E2-treated mice, immunized against genital HSV-2, coincided with earlier recruitment and higher proportions of Th1 and Th17 effector cells in the vagina post-challenge, compared to placebo-treated controls. Vaginal APCs isolated from E2-treated mice induced 10-fold higher Th17 and Th1 responses, compared to APCs from progesterone-treated, placebo-treated, and estradiol-receptor knockout mice in APC-T cell co-cultures. CD11c+ DCs in the vagina were the predominant APC population responsible for priming these Th17 responses, and a potent source of IL-6 and IL-1β, important factors for Th17 differentiation. Th17 responses were abrogated in APC-T cell co-cultures containing IL-1β KO, but not IL-6 KO vaginal DCs, showing that IL-1β is a critical factor for Th17 induction in the genital tract. E2 treatment in vivo directly induced high expression of IL-1β in vaginal DCs, and addition of IL-1β restored Th17 induction by IL-1β KO APCs in co-cultures. Finally, we examined the role of IL-17 in anti-HSV-2 memory T cell responses. IL-17 KO mice were more susceptible to intravaginal HSV-2 challenge, compared to WT controls, and vaginal DCs from these mice were defective at priming efficient Th1 responses in vitro, indicating that IL-17 is important for the generation of efficient anti-viral memory responses. We conclude that the genital mucosa has a unique microenvironment whereby E2 enhances CD4+ T cell anti-viral immunity by priming vaginal DCs to induce Th17 responses through an IL-1-dependent pathway. PMID:27148737

    13. Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis.

      PubMed

      Murphy, Aine C; Lalor, Stephen J; Lynch, Marina A; Mills, Kingston H G

      2010-05-01

      Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis, where disease is mediated by autoantigen-specific T cells. Although there is evidence linking CD4(+) T cells that secrete IL-17, termed Th17 cells, and IFN-gamma-secreting Th1 cells with the pathogenesis of EAE, the precise contribution of these T cell subtypes or their associated cytokines is still unclear. We have investigated the infiltration of CD4(+) T cells that secrete IFN-gamma, IL-17 or both cytokines into CNS during development of EAE and have examined the role of T cells in microglial activation. Our findings demonstrate that Th17 cells and CD4(+) T cells that produce both IFN-gamma and IL-17, which we have called Th1/Th17 cells, infiltrate the brain prior to the development of clinical symptoms of EAE and that this coincides with activation of CD11b(+) microglia and local production of IL-1beta, TNF-alpha and IL-6 in the CNS. In contrast, significant infiltration of Th1 cells was only detected after the development of clinical disease. Co-culture experiments, using mixed glia and MOG-specific T cells, revealed that T cells that secreted IFN-gamma and IL-17 were potent activators of pro-inflammatory cytokines but T cells that secrete IFN-gamma, but not IL-17, were less effective. In contrast both Th1 and Th1/Th17 cells enhanced MHC-class II and co-stimulatory molecule expression on microglia. Our findings suggest that T cells which secrete IL-17 or IL-17 and IFN-gamma infiltrate the CNS prior to the onset of clinical symptoms of EAE, where they may mediate CNS inflammation, in part, through microglial activation. Copyright 2010 Elsevier Inc. All rights reserved.

    14. Electrical muscle stimulation in thomboprophylaxis: review and a derived hypothesis about thrombogenesis-the 4th factor.

      PubMed

      Stefanou, Christos

      2016-01-01

      Electrical muscle stimulation (EMS) is an FDA-approved thromboprophylactic method. Thrombus pathogenesis is considered to depend on factors related to components of the vessel wall, the velocity of blood, and blood consistency-collectively known as, the Virchow's triad. The testimony supporting the thromboprophylactic effects of the EMS is reviewed. An emphasis is placed on the fact that, EMS has demonstrated, in certain circumstances, an efficacy rate that cannot be fully explained by the Virchow's triad; also that, in reviewing relevant evidence and the theorized pathophysiological mechanisms, several findings collectively point to a potentially missed point. Remarkably, venous thromboembolic disease (VTE) is extremely more common in the lower versus the upper extremities even when the blood velocities equalize; EMS had synergistic effects with intermittent compressive devices, despite their presumed identical mechanism of action; sleep is not thrombogenic; non-peroperative EMS is meaningful only if applied ≥5 times daily; neural insult increases VTEs more than the degree expected by the hypomobility-related blood stasis; etc. These phenomena infer the presence of a 4th thrombogenetic factor: neural supply to the veins provides direct antithrombic effects, by inducing periodic vessel diameter changes and/or by neuro-humoral, chemically acting factors. EMS may stimulate or substitute the 4th factor. This evidence-based hypothesis is analyzed. A novel pathophysiologic mechanism of thrombogenesis is supported; and, based on this, the role of EMS in thromboprophylaxis is expanded. Exploration of this mechanism may provide new targets for intervention.

    15. CXCL4 is a novel inducer of human Th17 cells and correlates with IL-17 and IL-22 in psoriatic arthritis.

      PubMed

      Affandi, Alsya J; Silva-Cardoso, Sandra C; Garcia, Samuel; Leijten, Emmerik F A; van Kempen, Tessa S; Marut, Wioleta; van Roon, Joel A G; Radstake, Timothy R D J

      2018-03-01

      CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL-17 production by human CD4 + T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4 + T cells to secrete IL-17 that co-expressed IFN-γ and IL-22, and differentiated naïve CD4 + T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4 + T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen. Moreover, when monocyte-derived dendritic cells were differentiated in the presence of CXCL4, they orchestrated increased levels of IL-17, IFN-γ, and proliferation by CD4 + T cells. Furthermore, the CXCL4 levels in synovial fluid from psoriatic arthritis patients strongly correlated with IL-17 and IL-22 levels. A similar response to CXCL4 of enhanced IL-17 production by CD4 + T cells was also observed in patients with psoriatic arthritis. Altogether, we demonstrate that CXCL4 boosts pro-inflammatory cytokine production especially IL-17 by human CD4 + T cells, either by acting directly or indirectly via myeloid antigen presenting cells, implicating a role for CXCL4 in PsA pathology. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    16. CXCL4 is a novel inducer of human Th17 cells and correlates with IL‐17 and IL‐22 in psoriatic arthritis

      PubMed Central

      Affandi, Alsya J.; Silva‐Cardoso, Sandra C.; Garcia, Samuel; Leijten, Emmerik F. A.; van Kempen, Tessa S.; Marut, Wioleta; van Roon, Joel A. G.

      2018-01-01

      Abstract CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17‐associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL‐17 production by human CD4+ T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4+ T cells to secrete IL‐17 that co‐expressed IFN‐γ and IL‐22, and differentiated naïve CD4+ T cells to become Th17‐cytokine producing cells. In a co‐culture system of human CD4+ T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL‐17 production upon triggering by superantigen. Moreover, when monocyte‐derived dendritic cells were differentiated in the presence of CXCL4, they orchestrated increased levels of IL‐17, IFN‐γ, and proliferation by CD4+ T cells. Furthermore, the CXCL4 levels in synovial fluid from psoriatic arthritis patients strongly correlated with IL‐17 and IL‐22 levels. A similar response to CXCL4 of enhanced IL‐17 production by CD4+ T cells was also observed in patients with psoriatic arthritis. Altogether, we demonstrate that CXCL4 boosts pro‐inflammatory cytokine production especially IL‐17 by human CD4+ T cells, either by acting directly or indirectly via myeloid antigen presenting cells, implicating a role for CXCL4 in PsA pathology. PMID:29193036

    17. An Evaluation of Factors Affecting Decision Making among 4th Grade Elementary School Students with Low Socio-Economic Status

      ERIC Educational Resources Information Center

      Kaskaya, Alper; Calp, Sükran; Kuru, Oguzhan

      2017-01-01

      Decision making is one of the most important life skills. While making correct, timely, accurate and appropriate decisions lead to positive changes in one's life, making incorrect decisions may have a negative impact. It is an important issue to examine what the 4th grade students in primary school have about the decision-making ability to be…

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

      PubMed

      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.

    19. Relationship between Long Working Hours and Suicidal Thoughts: Nationwide Data from the 4th and 5th Korean National Health and Nutrition Examination Survey.

      PubMed

      Yoon, Jin-Ha; Jung, Pil Kyun; Roh, Jaehoon; Seok, Hongdeok; Won, Jong-Uk

      2015-01-01

      Long working hours are a worldwide problem and may increase the risk of various health issues. However, the health effects of long working hours on suicidal thoughts have not been frequently studied. Our goal was to investigate the relationship between long working hours and suicidal thoughts in the rapidly developing country of Korea. Data from 12,076 participants (7,164 men, 4,912 women) from the 4th and 5th Korean National Health and Nutrition Examination Surveys were used for the current analysis. Multivariate logistic regression models were used to estimate odds ratios and 95% confidence intervals for suicidal thoughts. Combined effects of long working hours and lower socioeconomic status or sleep disturbance were also estimated. Compared to groups who worked less than 52 hours per week, odds ratios (95% confidence intervals) for suicidal thoughts in groups who worked 60 hours or more per week were 1.36 (1.09-1.70) for males and 1.38 (1.11-1.72) for females, even after controlling for household income, marital status, history of hypertension or diabetes mellitus, health-related behaviors, and past two weeks' experience of injury, intoxication, or acute or chronic diseases, as well as type of work. The combined effects of long working hours with lower socioeconomic status, or with sleep disturbance, were also significantly higher compared to participants who worked less than 52 hours per week with higher socioeconomic status, or with 6-8 hours of nighttime sleep. In this study, long working hours were linked to suicidal thoughts for both genders. Additionally, the odds of those suicidal thoughts were higher for lower socioeconomic groups. To prevent adverse psychological health problems such as suicidal thoughts, a strategy regarding long working hours should be investigated.

    20. Relationship between Long Working Hours and Suicidal Thoughts: Nationwide Data from the 4th and 5th Korean National Health and Nutrition Examination Survey

      PubMed Central

      Yoon, Jin-Ha; Jung, Pil Kyun; Roh, Jaehoon; Seok, Hongdeok; Won, Jong-Uk

      2015-01-01

      Background Long working hours are a worldwide problem and may increase the risk of various health issues. However, the health effects of long working hours on suicidal thoughts have not been frequently studied. Our goal was to investigate the relationship between long working hours and suicidal thoughts in the rapidly developing country of Korea. Methods Data from 12,076 participants (7,164 men, 4,912 women) from the 4th and 5th Korean National Health and Nutrition Examination Surveys were used for the current analysis. Multivariate logistic regression models were used to estimate odds ratios and 95% confidence intervals for suicidal thoughts. Combined effects of long working hours and lower socioeconomic status or sleep disturbance were also estimated. Results Compared to groups who worked less than 52 hours per week, odds ratios (95% confidence intervals) for suicidal thoughts in groups who worked 60 hours or more per week were 1.36 (1.09–1.70) for males and 1.38 (1.11–1.72) for females, even after controlling for household income, marital status, history of hypertension or diabetes mellitus, health-related behaviors, and past two weeks’ experience of injury, intoxication, or acute or chronic diseases, as well as type of work. The combined effects of long working hours with lower socioeconomic status, or with sleep disturbance, were also significantly higher compared to participants who worked less than 52 hours per week with higher socioeconomic status, or with 6–8 hours of nighttime sleep. Conclusion In this study, long working hours were linked to suicidal thoughts for both genders. Additionally, the odds of those suicidal thoughts were higher for lower socioeconomic groups. To prevent adverse psychological health problems such as suicidal thoughts, a strategy regarding long working hours should be investigated. PMID:26080022

    1. Properties of Fr-like Th^3+ from microwave spectroscopy of high-L Rydberg states of Th^2+

      NASA Astrophysics Data System (ADS)

      Keele, Julie; Smith, Chris; Woods, Shannon; Lundeen, Stephen; Fehrenbach, Charles

      2012-06-01

      Spectroscopy of high-L n= 28 Rydberg levels of Th^2+ was recently reported using the optical RESIS method [1]. Because the ground state of Fr-like Th^3+ is a ^2F5/2 level, each (n,L) Rydberg level of Th^2+ is split into six eigenstates whose relative positions are determined by long-range e-Th^3+ interactions. Measurements of those positions can be used to determine the Th^3+ properties that control those interactions, such as polarizabilities and permanent moments. We report a much improved study of n=28 levels with 9 <= L <= 12, obtained with the microwave/RESIS method. The higher precision measurements allow improved determinations of a wider range of Th^3+ properties and a better test of theoretical calculations [2].[4pt] [1] Julie A. Keele, M.E. Hanni, Shannon L. Woods, S.R. Lundeen, and C.W. Fehrenbach, Phys. Rev. A 83, 062501 (2011)[0pt] [2] U.I. Safronova, W.R. Johnson, and M.S. Safronova, Phys. Rev. A 74, 042511 (2006)

    2. [Clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis].

      PubMed

      Wu, H Q; Zhao, J J; Li, H W; Zhang, Z

      2017-10-20

      Objective: To investigate the clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis, and to explore immune therapeutic strategies for targeted therapy for liver cirrhosis. Methods: In vitro peripheral blood mononucleated cells (PBMCs) were collected by centrifugation. CD3-BV500 and CD8-PerCP-Cy5.5 staining was performed for these cells. IFNγ-PE-Cy7, IL-17a-APC, IL-22-PE, or the corresponding isotype control was added, and then PBMCs were fixed with 1% polyoxymethylene after being washed once by permeabilization-wash buffer. Flowjo software was used for the analysis of T lymphocyte subsets and cytokines. Th1 (CD4+IFNγ(+)), Th17 (CD4+IL-17a(+)), Th22 (CD4+IL-22(+)), Tc1 (CD8+IFNγ(+)), Tc17 (CD8+IL-17a(+)), and Tc22 (CD8+IL-22(+)) subsets were defined and the secretions of interferon-γ (IFN-γ), interleukin-17a (IL-17a), and interleukin-22 (IL-22) were measured for all subsets. LX-2 cells were cultured in a serum-free medium and different concentrations of recombinant human IL-22 protein (25, 50, 100 ng/ml) were added; 24 hours later, the activation marker α-smooth muscle actin (α-SMA) was used to measure LX-2 activation. Fetal bovine serum with a volume fraction of 10% was used as a positive control. Enzyme-linked immunosorbent assay (chemiluminescence) was used to measure the concentrations of hyaluronic acid, type III precollagen, and type IV collagen in supernatant. A one-way analysis of variance, the non-parametric Mann-Whitney U test, and the non-parametric Kruskal-wallis H test were used for statistical analysis based on data type. Results: Compared with the health control group, the liver cirrhosis groups with various causes had significant increases in peripheral Tc1, Th17, and Th22 cells. The percentage of Th17 cells in the liver cirrhosis group was 1.64 times that in the control group (4.25%±2.45% vs 2.59%±1.36%, P < 0.05), and the mean percentage of Th22 cells in the

    3. Splanchnic Th(2) and Th(1) cytokine redistribution in microsurgical cholestatic rats.

      PubMed

      García-Dominguez, José; Aller, María-Angeles; García, Cruz; de Vicente, Felipe; Corcuera, Maria-Teresa; Gómez-Aguado, Fernando; Alonso, María José; Vara, Elena; Arias, Jaime

      2010-08-01

      Long-term extrahepatic cholestasis in the rat induces ductular proliferation and fibrosis in the liver, portal hypertension, splenomegaly, portosystemic collateral circulation, and ascites. These splanchnic alterations could have an inflammatory pathophysiology. We measured serum levels of hepatobiliary injury markers and the acute phase proteins, alpha-1-major acid protein (alpha(1)-MAP) and alpha-1-acid glycoprotein (alpha(1)-GPA) in rats 6 wk after microsurgical extrahepatic cholestasis. We also assayed Th(1) (TNF-alpha and IL-1beta) and Th(2) (IL-4 and IL-10) cytokine levels in the liver, ileum, spleen, and mesenteric lymph complex by enzyme-linked immunosorbent assay (ELISA) techniques. Liver fibrosis was measured by Sirius red stain and by using an image system computer-assisted method and mast cell liver infiltration by Giemsa stain. The cholestatic rats showed an increase (P<0.001) in serum levels of bile acids, total and direct bilirubin, AST, ALT, AST/ALT index, gamma-GT, alkaline phosphatase, alpha(1)- MAP, alpha(1)-GPA, and LDH (P<0.05) in relation to sham-operated rats. TNF-alpha, IL-1beta, IL-4, and IL-10 increased in the ileum (P<0.01) and mesenteric lymph complex (P<0.001), and decreased in the liver (P<0.001). A marked bile proliferation associated with fibrosis (P<0.001) and mast cell infiltration was also shown in the liver of cholestatic rats. The splanchnic redistribution of cytokines, with an increase of Th(1) and Th(2) production in the small bowel and in the mesenteric lymph complex, supports the key role of inflammatory mechanisms in rats with secondary biliary fibrosis. Copyright 2010 Elsevier Inc. All rights reserved.

    4. High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

      PubMed

      Goon, Peter K C; Hanon, Emmanuel; Igakura, Tadahiko; Tanaka, Yuetsu; Weber, Jonathan N; Taylor, Graham P; Bangham, Charles R M

      2002-05-01

      CD4(+) T cells are critical for inducing and maintaining efficient humoral and cellular immune responses to pathogens. The CD4(+) T-cell response in human T-lymphotropic virus 1 (HTLV-1) infection has not been studied in detail. However, CD4(+) T cells have been shown to predominate in early lesions in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We present direct estimates of HTLV-1 Env- and Tax-specific CD4(+) T-cell frequencies in patients infected with HTLV-1. We first showed that there was a strong bias toward the Th1 phenotype in these HTLV-1-specific CD4(+) T cells in patients with HAM/TSP. We then demonstrated significantly higher frequencies of HTLV-1-specific Th1-type CD4(+) T cells in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The majority of these HTLV-1-specific CD4(+) T cells did not express HTLV-1 Tax and were therefore unlikely to be infected by HTLV-1. High frequencies of activated HTLV-1-specific CD4(+) T cells of the Th1 phenotype might contribute to the initiation or pathogenesis of HAM/TSP and other HTLV-1-associated inflammatory diseases.

    5. AHR-Enhancing γδ T Cells Develop in Normal Untreated Mice and Fail to Produce IL-4/13, Unlike TH2 Cells and NKT Cells1

      PubMed Central

      Jin, Niyun; Roark, Christina L.; Miyahara, Nobuaki; Taube, Christian; Aydintug, M. Kemal; Wands, JM; Huang, Yafei; Hahn, Youn-Soo; Gelfand, Erwin W.; O’Brien, Rebecca L.; Born, Willi K.

      2008-01-01

      Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like iNKT cells, develops under the influence of enhancing and inhibitory γδ T cells. The AHR-enhancing cells belong to the Vγ1+ γδ T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR-enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSAhi maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-γ, TNFRp75 or IL-4 did not produce these AHR-enhancing γδ T cells, but in the absence of IFN-γ, their spontaneous development was restored by adoptive transfer of IFN-γ competent dendritic cells from untreated donors. Intra-peritoneal injection of OVA/alum restored development of the AHR-enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-γ or IL-4 in order to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing γδ T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR. PMID:19201853

    6. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

      PubMed

      Huang, T J; MacAry, P A; Eynott, P; Moussavi, A; Daniel, K C; Askenase, P W; Kemeny, D M; Chung, K F

      2001-01-01

      Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.

    7. Th9 cells: differentiation and disease

      PubMed Central

      Kaplan, Mark H.

      2014-01-01

      Summary CD4+ T-helper cells regulate immunity and inflammation through the acquisition of potential to secrete specific cytokines. The acquisition of cytokine-secreting potential, in a process termed T-helper cell differentiation, is a response to multiple environmental signals including the cytokine milieu. The most recently defined subset of T-helper cells are termed Th9 and are identified by the potent production of interleukin-9 (IL-9). Given the pleiotropic functions of IL-9, Th9 cells might be involved in pathogen immunity and immune-mediated disease. In this review, I focus on recent developments in understanding the signals that promote Th9 differentiation, the transcription factors that regulate IL-9 expression, and finally the potential roles for Th9 cells in immunity in vivo. PMID:23405898

    8. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection.

      PubMed

      Abo-Aziza, Faten A M; Hendawy, Seham H M; Namaky, Amira H El; Ashry, Heba M

      2017-06-01

      The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done concerning Th1/Th2 balance and cross-reactivity of S

    9. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection

      PubMed Central

      Abo-Aziza, Faten A. M.; Hendawy, Seham H. M.; Namaky, Amira H. El; Ashry, Heba M.

      2017-01-01

      Aim:: The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. Materials and Methods:: A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). Results:: The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Conclusion:: Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done

    10. Performance simulation of a detector for 4th generation photon sources: The AGIPD

      NASA Astrophysics Data System (ADS)

      Potdevin, G.; Trunk, U.; Graafsma, H.; Agipd Consortium

      2009-08-01

      Future 4th generation photon sources, such as the European XFEL based in Hamburg, will deliver around 1012 X-ray photons in less than 100 fs with full lateral coherence. These new sources will offer unprecedented possibilities in photon science. The high peak brilliance, combined with a 5 MHz repetition rate poses very high demands for the 2D detectors. In order to provide appropriate detectors during XFEL startup, three dedicated development projects have been initiated, one of them being the Adaptive Gain Integrating Pixel Detector (AGIPD) project which is a collaborative effort between DESY, PSI, University of Bonn, and University of Hamburg. An essential part of the AGIPD project is the development of a simulation tool for the complete detection system. The simulation tool as well as preliminary simulations of the detector characteristics is presented.

    11. European Code against Cancer 4th Edition: Process of reviewing the scientific evidence and revising the recommendations.

      PubMed

      Minozzi, Silvia; Armaroli, Paola; Espina, Carolina; Villain, Patricia; Wiseman, Martin; Schüz, Joachim; Segnan, Nereo

      2015-12-01

      The European Code Against Cancer is a set of recommendations to give advice on cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003. Working Groups of independent experts from different fields of cancer prevention were appointed to review the recommendations, supported by a Literature Group to provide scientific and technical support in the assessment of the scientific evidence, through systematic reviews of the literature. Common procedures were developed to guide the experts in identifying, retrieving, assessing, interpreting and summarizing the scientific evidence in order to revise the recommendations. The Code strictly followed the concept of providing advice to European Union citizens based on the current best available science. The advice, if followed, would be expected to reduce cancer risk, referring both to avoiding or reducing exposure to carcinogenic agents or changing behaviour related to cancer risk and to participating in medical interventions able to avert specific cancers or their consequences. The information sources and procedures for the review of the scientific evidence are described here in detail. The 12 recommendations of the 4th edition of the European Code Against Cancer were ultimately approved by a Scientific Committee of leading European cancer and public health experts. Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.

    12. Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice

      PubMed Central

      Feng, Yu; Tian, Jijing; Xie, Heidi Qunhui; She, Jianwen; Xu, Sherry Li; Xu, Tuan; Tian, Wenjing; Fu, Hualing; Li, Shuaizhang; Tao, Wuqun; Wang, Lingyun; Chen, Yangsheng; Zhang, Songyan; Zhang, Wanglong; Guo, Tai L.; Zhao, Bin

      2016-01-01

      Background: Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. Objectives: We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. Methods: Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). Results: Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. Conclusions: To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. Citation: Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y

    13. PREFACE: 4th International Hadron Physics Conference (TROIA'14)

      NASA Astrophysics Data System (ADS)

      Dağ, Hüseyin; Erkol, Güray; Küçükarslan, Ayşe; Özpineci, Altuğ

      2014-11-01

      The 4th International Conference on Hadron Physics, TROIA'14, was held at Canakkale, Turkey on 1-5 July 2014. Ozyegin University, Middle East Technical University, Canakkale Onsekiz Mart University, Turkish Atomic Energy Authority and HadronPhysics2 Consortium sponsored the conference. It aimed at bringing together the experts and the young scientists working on experimental and theoretical hadron physics. About 50 participants from 10 countries attended the conference. The topics covered included: . Chiral Perturbation Theory . QCD Sum Rules . Effective Field Theory . Exotic Hadrons . Hadron Properties from Lattice QCD . Experimental Results and Future Perspectives . Hadronic Distribution Amplitudes The conference presentations were organized such that the morning sessions contained invited talks and afternoon sessions were devoted to contributed talks. The speakers of the invited talks were: C. Alexandrou, A. Gal, L. Tolos, J.R. Pelaez and M. Schindler. We had also guest speakers D. A. Demir and T. Senger. The conference venue was a resort hotel around Canakkale. As a social program, a guided full-day excursion to the excavation site of the ancient Troia town and Assos was organized. We believe that this conference provided a medium for young scientists and experts in the field to effectively communicate and share ideas. We would like to express our sincere thanks to supporting agencies and to all participants for their contributions and stimulating discussions. We are also grateful to the Scientific Secretary, Bora Işıldak, and all other members of the Organizing Committee for their patience and efforts. 30.10.2014 The Editors

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

      PubMed

      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 < 0.05). After EA intervention, the increased DAI score and the ratio of Th 17/CD⁸⁺ T cells and the decreased Treg/CD⁴⁺ T cells were reversed (P < 0.05), and the inflammatory cell infiltration degree of the colon tissue was attenuated. EA intervention can improve the, UC rats' symptoms of activity state, bloody or viscidity stool and colonic inflammation, probably by regulating the balance between the spleenic Treg and Th 17 lymphocytes.

    15. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, volume 1

      NASA Technical Reports Server (NTRS)

      Krishen, Kumar (Editor); Burnham, Calvin (Editor)

      1995-01-01

      The papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held at the Marriott Orlando World Center, Orlando, Florida, are contained in this document and encompass the research, technology, applications, funding, political, and social aspects of superconductivity. Specifically, the areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges, and power and energy applications.

    16. Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients.

      PubMed

      Libetta, C; Rampino, T; Dal Canton, A

      2001-08-01

      T-helper (Th) lymphocytes consist of Th1 and Th2 subsets. Th1 cells are effectors of cell-mediated immunity and secrete interferon-gamma (IFN-gamma), which recruits new Th1 cells in cooperation with interleukin-12 (IL-12; produced by monocytes) and inhibits Th2 differentiation. Th2 cells produce IL-4 and IL-10, which inhibit IFN-gamma secretion and cell immunity. We investigated whether the impaired immune response in uremia is associated with an altered balance of Th1/Th2. Peripheral-blood mononuclear cells (PBMCs) were collected from patients with chronic renal failure (CRF) on conservative treatment (CRF patients), patients with end-stage renal disease (ESRD) on regular hemodialysis therapy (ESRD-HD patients), and healthy controls (CON). CD4(+) cells were isolated from PBMCs by negative selection using a magnetic labeling system. PBMCs and purified CD4(+) cells were cultured in Iscove's medium and Iscove's medium plus mitogens (phytohemagglutinin and lipopolysaccharide). IFN-gamma, IL-12, IL-4, and IL-10 were measured in supernatant. The constitutive release of IL-4 and IL-10 by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was increased by five to eight times in comparison with CON (P < 0.001). Constitutive IFN-gamma release by PBMCs of ESRD-HD patients was undetectable, although they secreted an increased amount of IL-12. Mitogen-stimulated release of IFN-gamma by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was blunted (average PBMCs: CON, 115.8 pg/2 x10(6) cells; CRF, 81.8 pg/2 x10(6) cells; ESRD-HD, 9.3 pg/2 x10(6) cells; CD4(+) cells: CON, 358.0 pg/5 x 10(5) cells; CRF, 165.4 pg/5 x 10(5) cells; ESRD-HD, 43.5 pg/5 x 10(5) cells). The ability of PBMCs of ESRD-HD patients to secrete IFN-gamma was recovered after IL-4 and IL-10 neutralization. Uremia is associated with a prevalence of Th1 over Th2 cells and a configuration of cytokine network that depresses cell-mediated immunity.

    17. Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders.

      PubMed

      Szodoray, Peter; Nakken, Britt; Barath, Sandor; Csipo, Istvan; Nagy, Gabor; El-Hage, Fadi; Osnes, Liv T; Szegedi, Gyula; Bodolay, Edit

      2013-12-01

      A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3 years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4(+)CD25(bright)FoxP3(+); nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

    18. Magnolol Attenuates Concanavalin A-induced Hepatic Fibrosis, Inhibits CD4+ T Helper 17 (Th17) Cell Differentiation and Suppresses Hepatic Stellate Cell Activation: Blockade of Smad3/Smad4 Signalling.

      PubMed

      Zhang, Hongjun; Ju, Baoling; Zhang, Xiaoli; Zhu, Yanfei; Nie, Ying; Xu, Yuanhong; Lei, Qiuxia

      2017-06-01

      Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo. In response to ConA stimulation, the CD4 + T cells preferred to polarizing towards CD4 + T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA-treated liver in addition to suppressing interleukin (IL)-17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α-SMA) and desmin. More transforming growth factor (TGF)-β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro, the recombinant IL-17A plus TGF-β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up-regulated phospho-Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell-mediated fibrosis. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

    19. Autism: Proceedings of Annual Meeting of the National Society for Autistic Children (4th, June 22-24, 1972, Flint Michigan).

      ERIC Educational Resources Information Center

      National Society for Autistic Children, Syracuse, NY.

      Presented are proceedings of the 4th annual (1972) meeting of the National Society for Autistic Children including 11 papers given at the meeting. Listed are officers and board members of the society, the convention committee members, and recipients of citations and awards. The president's report notes past goals, accomplishments, and future…

    20. A global perspective for managing obesity and improving health: conventional treatment and surgical options: 4th Annual Obesity Summit, London, April 2016.

      PubMed

      Ahmad, Adeel Nazir; Edwards, Kimberley L

      2016-12-01

      4th Annual Obesity Summit, London, 12-14 April 2016 There are more than 1.9 billion overweight people worldwide, culminating in high rates of Type 2 diabetes; and cardiovascular, digestive and other health problems. This makes obesity a startling phenomenon and a significant global health epidemic. To address this, The 2016 Obesity Summit, 4th in the series of obesity-related annual events organized by EuroSciCon, was held from 12 to 14 April 2016 at Cineworld, The O2 in London. This conference set the stage for three days of stimulating high-quality presentations on the advancements in obesity in an informal academic setting. Approximately 156 delegates including students, researchers, healthcare professionals and scientists from 36 countries around the world attended the event. This meeting report summarizes some of the most outstanding presentations.

    1. Local expression of vaginal Th1 and Th2 cytokines in murine vaginal candidiasis under different immunity conditions.

      PubMed

      Chen, Shanjuan; Li, Shaohua; Wu, Yan; Liu, Zhixiang; Li, Jiawen

      2008-08-01

      To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 (IL-2)/Th2 (IL-4, IL-10, TGF-beta1) cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-beta1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-beta1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans (C. albicans), and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.

    2. PREFACE: 9th World Congress on Computational Mechanics and 4th Asian Pacific Congress on Computational Mechanics

      NASA Astrophysics Data System (ADS)

      Khalili, N.; Valliappan, S.; Li, Q.; Russell, A.

      2010-07-01

      The use for mathematical models of natural phenomena has underpinned science and engineering for centuries, but until the advent of modern computers and computational methods, the full utility of most of these models remained outside the reach of the engineering communities. Since World War II, advances in computational methods have transformed the way engineering and science is undertaken throughout the world. Today, theories of mechanics of solids and fluids, electromagnetism, heat transfer, plasma physics, and other scientific disciplines are implemented through computational methods in engineering analysis, design, manufacturing, and in studying broad classes of physical phenomena. The discipline concerned with the application of computational methods is now a key area of research, education, and application throughout the world. In the early 1980's, the International Association for Computational Mechanics (IACM) was founded to promote activities related to computational mechanics and has made impressive progress. The most important scientific event of IACM is the World Congress on Computational Mechanics. The first was held in Austin (USA) in 1986 and then in Stuttgart (Germany) in 1990, Chiba (Japan) in 1994, Buenos Aires (Argentina) in 1998, Vienna (Austria) in 2002, Beijing (China) in 2004, Los Angeles (USA) in 2006 and Venice, Italy; in 2008. The 9th World Congress on Computational Mechanics is held in conjunction with the 4th Asian Pacific Congress on Computational Mechanics under the auspices of Australian Association for Computational Mechanics (AACM), Asian Pacific Association for Computational Mechanics (APACM) and International Association for Computational Mechanics (IACM). The 1st Asian Pacific Congress was in Sydney (Australia) in 2001, then in Beijing (China) in 2004 and Kyoto (Japan) in 2007. The WCCM/APCOM 2010 publications consist of a printed book of abstracts given to delegates, along with 247 full length peer reviewed papers published with

    3. Characterization of the Oxidation State of 229 Th Recoils Implanted in MgF2 for the Search of the Low-lying 229 Th Isomeric State

      NASA Astrophysics Data System (ADS)

      Barker, Beau; Meyer, Edmund; Schacht, Mike; Collins, Lee; Wilkerson, Marianne; Zhao, Xinxin

      2016-05-01

      The low-lying (7.8 eV) isomeric state in 229 Th has the potential to become a nuclear frequency standard. 229 Th recoils from 233 U decays have been collected in MgF2 for use in the direct search of the transition. Of interest is the oxidation state of the implanted 229 Th atoms as this can have an influence on the decay mechanisms and photon emission rate. Too determine the oxidation state of the implanted 229 Th recoils we have employed laser induced florescence (LIF), and plan-wave pseudopotential DFT calculations to search for emission from thorium ions in oxidation states less than + 4. Our search focused on detecting emission from Th3+ ions. The DFT calculations predicted the Th3+ state to be the most likely to be present in the crystal after Th4+. We also calculated the band structure for the Th3+ doped MgF2 crystal. For LIF spectra a number of excitation wavelengths were employed, emission spectra in the visible to near-IR were recorded along with time-resolved emission spectra. We have found no evidence for Th3+ in the MgF2 plates. We also analyzed the detection limit of our apprentice and found that the minimum number of Th3+ atoms that we could detect is quite small compared to the number of implanted 229 Th recoils. The number of implanted 229 Th recoils was derived from a γ-ray spectrum by monitoring emission from the daughters of 228 Th. These were present in the MgF2 plates due to a 232 U impurity, which decays to 228 Th, in the source. LA-UR-16-20442.

    4. Towards a 4{sup th} generation storage ring at the Canadian Light Source

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Dallin, Les; Wurtz, Ward

      2016-07-27

      Demands from beamline scientists for more brilliant sources of synchrotron radiation have resulted in the emergence of 4{sup th} generation (diffraction-limited) storage rings. The practical development of the multi-bend achromat (MBA) concept by MAX IV lab has spurred many synchrotron light sources around the world to develop similar machines. For existing facilities two options are available: upgrading existing machines or building a new structure. The Canadian Light Source (CLS) has explored both options. For a new low emittance source in the existing CLS tunnel a decrease in electron energy would be required. A machine similar to the ALS upgrade couldmore » be contemplated. To achieve low emittance at our present energy of 2.9 GeV a new storage ring is desirable. Several options have been investigated. These designs use extremely strong focusing magnets to achieve extremely low emittances in compact lattice achromats.« less

    5. Self-reported reasons for vaping among 8th, 10th, and 12th graders in the US: Nationally-representative results.

      PubMed

      Patrick, Megan E; Miech, Richard A; Carlier, Carola; O'Malley, Patrick M; Johnston, Lloyd D; Schulenberg, John E

      2016-08-01

      The study describes the most common reasons for using vaporizers (such as e-cigarettes) among US adolescents and investigates how reasons for use differ by grade, lifetime cigarette use, frequency of vaporizer use, gender, race/ethnicity, and parent education. Data were collected from 4066 students in the 8th, 10th, and 12th grades in 2015 as part of the Monitoring the Future study, a cross-sectional and nationally representative US survey. Common reasons for vaporizer use reported by respondents who had ever used a vaporizer were experimentation (53.0%), taste (37.2%), boredom (23.5%), having a good time (22.4%), and relaxation (21.6%). Reasons differed little across grades or parent education; reasons differed by lifetime use of regular cigarettes, frequency of vaping, gender, and race/ethnicity. Overall, results suggest that decisions to vape are based on curiosity, taste, and pleasure, rather than for reasons such as quitting regular cigarettes or substituting for regular cigarette smoking. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

    6. Arthrodesis of the proximal interphalangeal joint of the 4th and 5th finger using an interlocking screw device to treat severe recurrence of Dupuytren's disease.

      PubMed

      Novoa-Parra, C D; Montaner-Alonso, D; Pérez-Correa, J I; Morales-Rodríguez, J; Rodrigo-Pérez, J L; Morales-Suarez-Varela, M

      To assess the radiological and functional outcome of arthrodesis of the 4th and 5th finger using the APEX™ (Extremity Medical, Parsippany,NJ)intermedullary interlocking screw system in patients with severe recurrence of Dupuytren's disease. The DASH questionnaire and the VAS scale were used to assess the clinical outcomes. The angle of arthrodesis, fusion time and implant fixation were evaluated on x-rays. The patients were monitored for complications during surgery and the follow-up period. The sample comprised 6 patients. Mean follow up was 19.6 months. All of the patients presented clinical and radiological evidence of fusion at 8 weeks, with fusion angles of 30° (3) and 45° (3). There were no complications and none of the implants had to be removed. The functional outcomes in these patients were poor. The system offers a reliable method for IPJ arthrodesis at a precise angle. It promotes stable fixation that does not require prolonged immobilisation. It can be used together with other procedures on the hand with severe recurrence of DD. The functional outcomes for this group of patients using this device were poor. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

    7. Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice.

      PubMed

      Ma, Chun-Hua; Ma, Zhan-Qiang; Fu, Qiang; Ma, Shi-Ping

      2014-05-01

      Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM). This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells. These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

    8. Th17 cells in human disease

      PubMed Central

      Tesmer, Laura A.; Lundy, Steven K.; Sarkar, Sujata; Fox, David A.

      2012-01-01

      Summary Our understanding of the role of T cells in human disease is undergoing revision as a result of the discovery of T-helper 17 (Th17) cells, a unique CD4+ T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine with robust effects on stromal cells in many tissues. Recent data in humans and mice suggest that Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Initial reports also propose a role for Th17 cells in tumorigenesis and transplant rejection. Important differences, as well as many similarities, are emerging when the biology of Th17 cells in the mouse is compared with corresponding phenomena in humans. As our understanding of human Th17 biology grows, the mechanisms underlying many diseases are becoming more apparent, resulting in a new appreciation for both previously known and more recently discovered cytokines, chemokines, and feedback mechanisms. Given the strong association between excessive Th17 activity and human disease, new therapeutic approaches targeting Th17 cells are highly promising, but the potential safety of such treatments may be limited by the role of these cells in normal host defenses against infection. PMID:18613831

    9. Comparison of Values in 5th, 6th, 7th and 8th Grade Primary Education Music Class Students'? Workbooks According to Rokeach?s and Akbas's Value Classifications

      ERIC Educational Resources Information Center

      Çakirer, H. Serdar

      2014-01-01

      The aim of the present study is to compare the values in the songs of 5th, 6th, 7th and 8th grade primary education music classes students? workbooks according to the value categorizations proposed by Rockeach and Akbas and which values among the categories mentioned are taught to the students in the 5th, 6th, 7th and 8th grade primary education…

    10. Subcutaneous packing in royal Egyptian mummies dated from 18th to 20th dynasties.

      PubMed

      Saleem, Sahar N; Hawass, Zahi

      2015-01-01

      It has been widely disseminated in the literature that subcutaneous packing, as part of mummification, was not usually done until the 21st dynasty. We aimed to study by computed tomography (CT) if subcutaneous packing was part of mummification of royal Egyptians dated to 18th to 20th dynasties. We analyzed the 2- and 3-dimensional CT images of 13 royal mummies dated to circa 1550 to 1153 BC for presence of subcutaneous embalming materials. Among the studied mummies were Amenhotep III, Tutankhamun, Seti I, and Ramesses II. We reported the CT characters of any detected subcutaneous embalming materials and noted their impact on the morphology of the involved body part. We correlated the CT findings with the archeological literature. Computed tomographic images showed subcutaneous packing in 12 (92.3%) mummies; whereas the mummy that was previously known as "Thutmose I" showed no such evidence. Subcutaneous packing involved the faces (n = 11), necks (n = 4), torsos (n = 5), and/or extremities (n = 4) of the mummies. Subcutaneous filling materials showed variation in homogeneity and CT densities and they were likely composed of resin, bits of linen with resin, or other substances. Subcutaneous packing procedure succeeded in providing uniform full contour of the involved body regions without causing significant tissue damages. Subcutaneous packing procedure was used as part of mummification of royal Ancient Egyptians dated to 18th to 20th dynasties earlier than what was believed in archaeology. The Ancient Egyptian embalmers must have been skilled in dissection and possessed surgical tools that enabled them to perform this fine procedure.

    11. Nation and Language: Modern Aspects of Socio-Linguistic Development. Proceedings of the 4th International Conference (Lithuania, October 21-22, 2010)

      ERIC Educational Resources Information Center

      Online Submission, 2010

      2010-01-01

      The 4th international conference "Nation and Language: Modern Aspects of Socio-Linguistic Development" continues an eight-year old tradition. The conference is organized by Kaunas University of Technology Panevezys Institute and aims to bring scientists and researchers together for a general scientific discussion on new trends in…

    12. An ecological study of food desert prevalence and 4th grade academic achievement in new york state school districts.

      PubMed

      Frndak, Seth E

      2014-12-02

      This ecological study examines the relationship between food desert prevalence and academic achievement at the school district level. Sample included 232 suburban and urban school districts in New York State. Multiple open-source databases were merged to obtain: 4(th) grade science, English and math scores, school district demographic composition (NYS Report Card), regional socioeconomic indicators (American Community Survey), school district quality (US Common Core of Data), and food desert data (USDA Food Desert Atlas). Multiple regression models assessed the percentage of variation in achievement scores explained by food desert variables, after controlling for additional predictors. The proportion of individuals living in food deserts significantly explained 4th grade achievement scores, after accounting for additional predictors. School districts with higher proportions of individuals living in food desert regions demonstrated lower 4th grade achievement across science, English and math. Food deserts appear to be related to academic achievement at the school district level among urban and suburban regions. Further research is needed to better understand how food access is associated with academic achievement at the individual level. Significance for public healthThe prevalence of food deserts in the United States is of national concern. As poor nutrition in United States children continues to spark debate, food deserts are being evaluated as potential sources of low fruit and vegetable intake and high obesity rates. Cognitive development and IQ have been linked to nutrition patterns, suggesting that children in food desert regions may have a disadvantage academically. This research evaluates if an ecological relationship between food desert prevalence and academic achievement at the school district level can be demonstrated. Results suggest that food desert prevalence may relate to poor academic performance at the school district level. Significant variation in

    13. A Chemistry Course for High Ability 8th, 9th, and 10th Graders.

      ERIC Educational Resources Information Center

      Kilker, Richard, Jr.

      1985-01-01

      Describes a chemistry course designed, in cooperation with local public school districts, to intellectually challenge a group of 8th, 9th, and 10th grade students. Organic chemistry and biochemistry are integrated into the course (titled Chemistry and Everyday Life) to emphasize practical applications of chemistry. The course syllabus is included.…

    14. An Analysis of the Implementation of the Standard Accounting, Budgeting and Reporting System (SABRS) in the 4th Marine Division.

      DTIC Science & Technology

      1980-12-01

      REPOR DOCUMENTATION PAGE - 33703 COMPLZT!Nc PORN I.RPRNUM69M L. GOV"T ACCESSION NO. I. RECIPIEN4TS CATALOG NUNS9R a. TITLE (mds ume An Anaiysi s of th...wagging the dog ." The development schedule for SABRS envisions the three phases of concept formulation, Automated Data Systems (ADS) development and

    15. Examining Differentiation and Utilization of iPads across Content Areas in an Independent, PreK-4th Grade Elementary School

      ERIC Educational Resources Information Center

      Milman, Natalie B.; Carlson-Bancroft, Angela; Vanden Boogart, Amy

      2014-01-01

      This mixed methods case study examined the implementation of a 1:1 iPad initiative in a suburban, co-educational, independent, preK-4th grade elementary school in the United States. This article focuses on how teachers used iPads to differentiate instruction and across multiple content areas. Findings show the processes by which teachers employed…

    16. Transcription factor ThWRKY4 binds to a novel WLS motif and a RAV1A element in addition to the W-box to regulate gene expression.

      PubMed

      Xu, Hongyun; Shi, Xinxin; Wang, Zhibo; Gao, Caiqiu; Wang, Chao; Wang, Yucheng

      2017-08-01

      WRKY transcription factors play important roles in many biological processes, and mainly bind to the W-box element to regulate gene expression. Previously, we characterized a WRKY gene from Tamarix hispida, ThWRKY4, in response to abiotic stress, and showed that it bound to the W-box motif. However, whether ThWRKY4 could bind to other motifs remains unknown. In this study, we employed a Transcription Factor-Centered Yeast one Hybrid (TF-Centered Y1H) screen to study the motifs recognized by ThWRKY4. In addition to the W-box core cis-element (termed W-box), we identified that ThWRKY4 could bind to two other motifs: the RAV1A element (CAACA) and a novel motif with sequence of GTCTA (W-box like sequence, WLS). The distributions of these motifs were screened in the promoter regions of genes regulated by some WRKYs. The results showed that the W-box, RAV1A, and WLS motifs were all present in high numbers, suggesting that they play key roles in gene expression mediated by WRKYs. Furthermore, five WRKY proteins from different WRKY subfamilies in Arabidopsis thaliana were selected and confirmed to bind to the RAV1A and WLS motifs, indicating that they are recognized commonly by WRKYs. These findings will help to further reveal the functions of WRKY proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

    17. Nicotine evokes kinetic tremor by activating the inferior olive via α7 nicotinic acetylcholine receptors.

      PubMed

      Kunisawa, Naofumi; Iha, Higor A; Shimizu, Saki; Tokudome, Kentaro; Mukai, Takahiro; Kinboshi, Masato; Serikawa, Tadao; Ohno, Yukihiro

      2016-11-01

      Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and immunohistochemical studies using mice and rats to elucidate the mechanisms underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5-2mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the nACh receptor antagonist mecamylamine (MEC). The specific α7 nACh receptor antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor, whereas the α4β2 nACh antagonist dihydro-β-erythroidine (DHβE) or the peripheral α3β4 nACh antagonist hexamethonium showed no effects. Mapping analysis of Fos protein expression, a biological marker of neural excitation, revealed that a tremorgenic dose (1mg/kg) of nicotine region-specifically elevated Fos expression in the piriform cortex (PirC), medial habenula, solitary nucleus and inferior olive (IO) among 44 brain regions examined. In addition, similarly to the tremor responses, nicotine-induced Fos expression in the PirC and IO was selectively antagonized by MLA, but not by DHβE. Furthermore, an electrical lesioning of the IO, but not the PirC, significantly suppressed the induction of nicotine tremor. The present results suggest that nicotine elicits kinetic tremor in rodents by activating the IO neurons via α7 nACh receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

    18. Combined 4-component and relativistic pseudopotential study of ThO for the electron electric dipole moment search.

      PubMed

      Skripnikov, L V

      2016-12-07

      A precise theoretical study of the electronic structure of heavy atom diatomic molecules is of key importance to interpret the experiments in the search for violation of time-reversal (T) and spatial-parity (P) symmetries of fundamental interactions in terms of the electron electric dipole moment, eEDM, and dimensionless constant, k T,P , characterizing the strength of the T,P-odd pseudoscalar-scalar electron-nucleus neutral current interaction. The ACME collaboration has recently improved limits on these quantities using a beam of ThO molecules in the electronic H 3 Δ 1 state [J. Baron et al., Science 343, 269 (2014)]. We apply the combined direct relativistic 4-component and two-step relativistic pseudopotential/restoration approaches to a benchmark calculation of the effective electric field, E eff , parameter of the T,P-odd pseudoscalar-scalar interaction, W T,P , and hyperfine structure constant in Δ13 state of the ThO molecule. The first two parameters are required to interpret the experimental data in terms of the eEDM and k T,P constant. We have investigated the electron correlation for all of the 98 electrons of ThO simultaneously up to the level of the coupled cluster with single, double, and noniterative triple amplitudes, CCSD(T), theory. Contributions from iterative triple and noniterative quadruple cluster amplitudes for the valence electrons have been also treated. The obtained values are E eff = 79.9 GV/cm, W T,P = 113.1 kHz. The theoretical uncertainty of these values is estimated to be about two times smaller than that of our previous study [L. V. Skripnikov and A. V. Titov, J. Chem. Phys., 142, 024301 (2015)]. It was found that the correlation of the inner- and outer-core electrons contributes 9% to the effective electric field. The values of the molecule frame dipole moment of the Δ13 state and the H 3 Δ 1 →X 1 Σ + transition energy of ThO calculated within the same methods are in a very good agreement with the experiment.

    19. 4th annual primary care ethics conference: ethics education and lifelong learning

      PubMed Central

      Spicer, John; McKenzie-Edwards, Emma; Misselbrook, David

      2014-01-01

      Primary care ethics is a field of study that has recently found new life, with calls to establish the relevance of ethical discussion in general practice, to gather a body of literature and to carve out an intellectual space for primary care on the academic landscape of bioethics. In this report, we reflect on the key strands of the 4th primary care ethics conference held at the Royal Society of Medicine, on a theme of ethics education and lifelong learning: first, to produce insights that have relevance for policy and practice; and second, to illustrate the idea that not only is ethics relevant in primary care, but primary care is relevant in medical ethics. Core themes included the advantages and disadvantages of prescriptive ways of doing ethics in education, ethical reflection and potential risk to professional status, the need to deal with societal change and to take on board the insights gained from empirical work, whether this is about different kinds of fatherhood, or work on the causes of moral distress in healthcare workers. PMID:25949739

    20. Th17 Cells Coordinate with Th22 Cells in Maintaining Homeostasis of Intestinal Tissues and both are Depleted in SIV-Infected Macaques.

      PubMed

      Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S

      2014-05-01

      Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection.

    1. Th17 Cells Coordinate with Th22 Cells in Maintaining Homeostasis of Intestinal Tissues and both are Depleted in SIV-Infected Macaques

      PubMed Central

      Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

      2014-01-01

      Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection. PMID:25364618

    2. STO-2: Support for 4th Year Operations, Recovery, and Science ASU Co-I

      NASA Astrophysics Data System (ADS)

      Groppi, Christopher

      This is a Co-Investigator proposal for "STO-2: Support for 4th Year Operations, Recovery, and Science" with Prof. Christopher K. Walker (University of Arizona) as PI. As a participant in the STO-2 mission, ASU will participate in instrument design and construction, mission I&T, flight operations and data analysis. ASU has unique capabilities in the field of direct metal micromachining, which it will bring to bear on the STO-2 cold optical assembly, flight mixers and LO hardware. In addition, our extensive experience with receiver integration and test will supplement the capabilities of the PI institution during the I&T phase at the University of Arizona, CSBF (Palestine, TX) and in Antarctica. Both the ASU PI and student will also participate in data analysis and publication after the flight.

    3. Structure and Binding of Ionic Clusters in Th and Zr Chloride Melts

      NASA Astrophysics Data System (ADS)

      Akdeniz, Z.; Tosi, M. P.

      2001-11-01

      We discuss microscopic ionic models for the structure and the binding of small clusters which may exist as structural units in molten ThCl4 and ZrCl4 and in their mixtures with alkali halides according to Raman scattering studies of Photiadis and Papatheodorou. The models are adjusted to the two isolated tetrahedral molecules. Appreciably higher ionicity is found for ThCl4 than for ZrCl4, and this fact underlies the strikingly different behaviour of the two systems in the dense liquid state -in particular, a molecular-type structure for molten ZrCl4 against a structure including charged oligomers in molten ThCl4.

    4. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4.

      PubMed

      Im, S H; Barchan, D; Maiti, P K; Fuchs, S; Souroujon, M C

      2001-06-01

      Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-dependent Ab-mediated autoimmune disorders, in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1-type cells and costimulatory factors such as CD40 ligand (CD40L) contribute to disease pathogenesis by producing proinflammatory cytokines and by activating autoreactive B cells. In this study we demonstrate the capacity of CD40L blockade to modulate EAMG, and analyze the mechanism underlying this disease suppression. Anti-CD40L Abs given to rats at the chronic stage of EAMG suppress the clinical progression of the autoimmune process and lead to a decrease in the AChR-specific humoral response and delayed-type hypersensitivity. The cytokine profile of treated rats suggests that the underlying mechanism involves down-regulation of AChR-specific Th1-regulated responses with no significant effect on Th2- and Th3-regulated AChR-specific responses. EAMG suppression is also accompanied by a significant up-regulation of CTLA-4, whereas a series of costimulatory factors remain unchanged. Adoptive transfer of splenocytes from anti-CD40L-treated rats does not protect recipient rats against subsequently induced EAMG. Thus it seems that the suppressed progression of chronic EAMG by anti-CD40L treatment does not induce a switch from Th1 to Th2/Th3 regulation of the AChR-specific immune response and does not induce generation of regulatory cells. The ability of anti-CD40L treatment to suppress ongoing chronic EAMG suggests that blockade of CD40L may serve as a potential approach for the immunotherapy of MG and other Ab-mediated autoimmune diseases.

    5. U-Th-Pb isotope data indicate phanerozoic age for oxidation of the 3.4 Ga Apex Basalt

      NASA Astrophysics Data System (ADS)

      Li, Weiqiang; Johnson, Clark M.; Beard, Brian L.

      2012-02-01

      The occurrence of ferric oxides in Archean rocks has played an important role in discussions on the amount of free oxygen in the atmosphere of the ancient Earth. Recognizing that post-Archean weathering may also produce oxide minerals, drill cores have been used to obtain samples beneath the depth of Phanerozoic weathering. The first core of the Archean Biosphere Drilling Project (ABDP-1) documented hematite as alteration products in 3.4 Ga basalts from the Marble Bar area of the Pilbara Craton, NW Australia, and this has been used to infer the presence of an O2-bearing atmosphere in the Archean. It is possible, however, that despite recovery of samples from > 100 m depth, oxidation of the basalts occurred much younger than the depositional age. In this study, the age of oxidation of the Apex Basalt from the ABDP-1 drill core at Marble Bar is constrained by U-Th-Pb geochronology. Lead and U concentrations of the basalts from the ABDP-1 drill core vary greatly, between < 1-58 ppm and 0.08-1.04 ppm, respectively, whereas Th contents are more restricted (0.24-0.71 ppm). 206Pb/204Pb ratios are non-radiogenic and vary from 12.44 to 14.69. The linear array in terms of 206Pb/204Pb-207Pb/204Pb variations does not reflect an age but reflects two-component mixing between a non-radiogenic "ore lead" end member and a radiogenic "basalt lead" end member. The samples do not form isochrons on 238U/204Pb-206Pb/204Pb, 235U/204Pb-207Pb/204Pb, or 232Th/204Pb-208Pb/204Pb diagrams, indicating post-formation U and Pb addition. Comparison of measured U/Th ratios with "model" U/Th ratios calculated based on 208Pb/204Pb-206Pb/204Pb variations indicates that U enrichment most likely occurred in the last 200 Ma. The degree of U enrichment in the samples is correlated with Fe(III)/FeTotal ratios, indicating that U addition and oxidation were related, most likely reflecting penetration of oxygenated surface waters in the Phanerozoic along bedding planes and shear zones. These results

    6. 54th Yearbook of the National Reading Conference (San Antonio, Texas, December 1-4, 2004)

      ERIC Educational Resources Information Center

      Maloch, Beth, Ed.; Hoffman, James V., Ed.; Schallert, Diane L., Ed.; Fairbanks, Colleen M., Ed.; Worthy, Jo, Ed.

      2005-01-01

      This volume presents the 54th Yearbook of the National Reading Conference (NRC). The 2004 NRC conference, set in San Antonio, took place against a political backdrop in which the nature and substance of literacy research has become suspect. Given the current state of politically-driven research agendas, the focus of the 54th annual NRC…

    7. Th9 Cells: Probable players in ulcerative colitis pathogenesis.

      PubMed

      Shohan, Mojtaba; Elahi, Shokrollah; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud; Bagheri, Nader; Soltani, Emad

      2018-04-19

      T lymphocytes represent an important part of adaptive immune system undertaking different functions to regulate immune responses. CD4+ T cells are the most important activator cells in inflammatory conditions. Depending on the type of induced cells and inflamed sites, expression and activity of different subtypes of helper T cells are changed. Recent studies have confirmed the existence of a new subset of helper T lymphocytes called Th9. Naive T cells can differentiate into Th9 subtypes if they are exposed simultaneously by interleukin (IL) 4 and transforming growth factor β and also secondary activation of a complicated network of transcription factors such as interferon regulatory factor 4 (IRF4) and Smads which are essential for adequate induction of this phenotype. Th9 cells specifically produce interleukin 9 and their probable roles in promoting intestinal inflammation are being investigated in human subjects and experimental models of ulcerative colitis (UC). Recently, infiltration of Th9 cells, overexpression of IL-9, and certain genes associated with Th9 differentiation have been demonstrated in inflammatory microenvironment of UC. Intestinal oversecretion of IL-9 protein is likely to break down epithelial barriers and compromise tolerance to certain commensal microorganisms which leads to inflammation. Th9 pathogenicity has not yet been adequately explored in UC and they are far from being considered as inflammatory cells in this milieu, therefore precise understanding the role of these newly identified cells in particular their potential role in gut pathogenesis may enable us to develop novel therapeutic approaches for inflammatory bowel disease. So, this article tries to discuss the latest knowledge on the above-mentioned field.

    8. Activation of mixed glia by Abeta-specific Th1 and Th17 cells and its regulation by Th2 cells.

      PubMed

      McQuillan, K; Lynch, Marina A; Mills, Kingston H G

      2010-05-01

      Microglia are innate immune cells of the CNS, that act as antigen-presenting cells (APC) for antigen-specific T cells and respond to inflammatory stimuli, such as amyloid-beta (Abeta), resulting in the release of neurotoxic factors and pro-inflammatory cytokines. Astrocytes can also act as APC and modulate the function of microglia. However, the role of distinct T cell subtypes, in particular Th17 cells, in glial activation and subsequent modulatory effects of Th2 cells are poorly understood. Here, we generated Abeta-specific Th1, Th2, and Th17 cells and examined their role in modulating Abeta-induced activation of microglia in a mixed glial culture, a preparation which mimics the complex APC types in the brain. We demonstrated that mixed glia acted as an effective APC for Abeta-specific Th1 and Th17 cells. Addition of Abeta-specific Th2 cells suppressed the Abeta-induced IFN-gamma production by Th1 cells and IL-17 production by Th17 cells with glia as the APC. Co-culture of Abeta-specific Th1 or Th17 cells with glia markedly enhanced Abeta-induced pro-inflammatory cytokine production and expression of MHC class II and co-stimulatory molecules on the microglia. Addition of Abeta-specific Th2 cells inhibited Th17 cell-induced IL-1beta and IL-6 production by mixed glia and attenuated Th1 cell-induced CD86 and CD40 expression on microglia. The modest enhancement of MHC class II and CD86 expression on astrocytes by Abeta-specific Th1 and Th17 was not attenuated by Th2 cells. These data indicate that Abeta-specific Th1 and Th17 cells induce inflammatory activation of glia, and that this is in part regulated by Th2 cells. Copyright 2010 Elsevier Inc. All rights reserved.

    9. The shortest Th-Th distance from a new type of quadruple bond.

      PubMed

      Hu, Han-Shi; Kaltsoyannis, Nikolas

      2017-02-15

      Compounds featuring unsupported metal-metal bonds between actinide elements remain highly sought after yet confined experimentally to inert gas matrix studies. Notwithstanding this paucity, actinide-actinide bonding has been the subject of extensive computational research. In this contribution, high level quantum chemical calculations at both the scalar and spin-orbit levels are used to probe the Th-Th bonding in a range of zero valent systems of general formula LThThL. Several of these compounds have very short Th-Th bonds arising from a new type of Th-Th quadruple bond with a previously unreported electronic configuration featuring two unpaired electrons in 6d-based δ bonding orbitals. H 3 AsThThAsH 3 is found to have the shortest Th-Th bond yet reported (2.590 Å). The Th 2 unit is a highly sensitive probe of ligand electron donor/acceptor ability; we can tune the Th-Th bond from quadruple to triple, double and single by judicious choice of the L group, up to 2.888 Å for singly-bonded ONThThNO.

    10. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.

      1991-03-01

      Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less

    11. Identity and Diversity of Human Peripheral Th and T Regulatory Cells Defined by Single-Cell Mass Cytometry.

      PubMed

      Kunicki, Matthew A; Amaya Hernandez, Laura C; Davis, Kara L; Bacchetta, Rosa; Roncarolo, Maria-Grazia

      2018-01-01

      Human CD3 + CD4 + Th cells, FOXP3 + T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3 + CD4 + T cell compartment remains questionable. In this study, we examined CD3 + CD4 + T cell populations by single-cell mass cytometry. We characterize the CD3 + CD4 + Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell-associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3 + CD4 + Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4) + FOXP3 + Treg and CD183 (CXCR3) + T-bet + Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3 + CD4 + T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1-Th2-Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3 + CD4 + T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies. Copyright © 2017 by The American Association of Immunologists, Inc.

    12. [Impact on serum 5-HT and TH1/TH2 in patients of depressive disorder at acute stage treated with acupuncture and western medication].

      PubMed

      Liu, Yi; Feng, Hui; Mao, Hongjing; Mo, Yali; Yin, Yan; Liu, Wenjuan; Song, Mingfen; Wang, Shengdong

      2015-06-01

      To compare the difference in depression relief in the treatment of depressive disorder at the acute stage between the combined therapy of acupuncture and 5-HT (5-hydroxytryptamine) selective serotonini reuptake inhibitors (SSRIs) and the single application of SSRIs and explore the impact on the imbalance of 5-HT and TH1/TH2. Ninety cases of depressive disorder at the acute stage were randomized into a combined therapy group and a medication group, 45 cases in each one. In the medication group, SSRIs were prescribed forl oral administration, once or twice a day, continuously for 4 weeks. In the combined therapy group, on the basis of treatment as the medication group, acupuncture was combined. The main acupoints were Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), Fengchi (GB 20), Dazhui (GV 14) and Sishencong (EX-HN 1), once every two. days, continuously for 4 weeks. Before treatment, and after the 1st, 2nd and 4th weeks of treatment, the Hamilton depression scale (HAMD) was used to evaluate the depression severity. Separately, before and after the 4 weeks of treatment, the levels of serum 5-HT, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-10 (IL-10) were determined and compared with those in 45 cases of the healthy group. HAMD score was reduced in the 1st, 2nd and 4th weeks of treatment as compared with that before treatment in the combined therapy group (all P<0 01). HAMD score was reduced in the 2nd and 4th weeks of treatment as compared with that before treatment in the medication group (all P<0. 01). HAMD scores in the combined therapy group were lower than those in the medication group in the 1st, 2nd and 4th weeks of treatment (all P< 0. 01). Before treatment, in the combined therapy group and the medication group, the levels of serum 5-HT, IL-4 and IL-10 were all lower than those in the healthy group (all P<0. 01); the levels of IL-1β and IL-6 were higher than those in the healthy group (all P<0. 01). In the

    13. Seismic Waves, 4th order accurate

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      2013-08-16

      SW4 is a program for simulating seismic wave propagation on parallel computers. SW4 colves the seismic wave equations in Cartesian corrdinates. It is therefore appropriate for regional simulations, where the curvature of the earth can be neglected. SW4 implements a free surface boundary condition on a realistic topography, absorbing super-grid conditions on the far-field boundaries, and a kinematic source model consisting of point force and/or point moment tensor source terms. SW4 supports a fully 3-D heterogeneous material model that can be specified in several formats. SW4 can output synthetic seismograms in an ASCII test format, or in the SAC finarymore » format. It can also present simulation information as GMT scripts, whixh can be used to create annotated maps. Furthermore, SW4 can output the solution as well as the material model along 2-D grid planes.« less

    14. A comprehensive allometric analysis of 2nd digit length to 4th digit length in humans.

      PubMed

      Lolli, Lorenzo; Batterham, Alan M; Kratochvíl, Lukáš; Flegr, Jaroslav; Weston, Kathryn L; Atkinson, Greg

      2017-06-28

      It has been widely reported that men have a lower ratio of the 2nd and 4th human finger lengths (2D : 4D). Size-scaling ratios, however, have the seldom-appreciated potential for providing biased estimates. Using an information-theoretic approach, we compared 12 candidate models, with different assumptions and error structures, for scaling untransformed 2D to 4D lengths from 154 men and 262 women. In each hand, the two-parameter power function and the straight line with intercept models, both with normal, homoscedastic error, were superior to the other models and essentially equivalent to each other for normalizing 2D to 4D lengths. The conventional 2D : 4D ratio biased relative 2D length low for the generally bigger hands of men, and vice versa for women, thereby leading to an artefactual indication that mean relative 2D length is lower in men than women. Conversely, use of the more appropriate allometric or linear regression models revealed that mean relative 2D length was, in fact, greater in men than women. We conclude that 2D does not vary in direct proportion to 4D for both men and women, rendering the use of the simple 2D : 4D ratio inappropriate for size-scaling purposes and intergroup comparisons. © 2017 The Author(s).

    15. Meeting Materials for the 4th NRC Meeting on the Guidance for and the Review of EPA's Toxicological Assessment of Inorganic Arsenic

      EPA Science Inventory

      On December 2-3, 2015, the National Research Council (NRC) hosted the 4th meeting of the committee formed to peer review the draft IRIS assessment of inorganic arsenic. EPA presented background and overview materials during the public session on December 2nd. This information co...

    16. Ustekinumab in der Therapie der Pustulosis palmoplantaris - Eine Fallserie mit neun Patienten.

      PubMed

      Buder, Valeska; Herberger, Katharina; Jacobi, Arnd; Augustin, Matthias; Radtke, Marc Alexander

      2016-11-01

      Die Pustulosis palmoplantaris ist eine chronisch entzündliche Hauterkrankung, die mit bedeutenden Einschränkungen der Lebensqualität und der Belastbarkeit einhergeht. Aufgrund von Zulassungsbeschränkungen und einem häufig therapierefraktären Verlauf sind die Behandlungsmöglichkeiten limitiert. Nach zuvor frustranen Therapien erhielten 9 Patienten mit Pustulosis palmoplantaris nach Ausschluss einer latenten Tuberkulose Ustekinumab (45 mg Ustekinumab bei < 100 kg Körpergewicht [KG], 90 mg Ustekinumab > 100 kg KG) in Woche 0, 4, 12 und 24. Reguläre Visiten erfolgten nach 4 und 12 Wochen, im weiteren Verlauf alle 12 Wochen. Das Durchschnittsalter bei Therapiebeginn betrug 48 Jahre. Drei Patienten waren männlich. Bei n  =  4 Patienten (44,4 %) wurde eine Verbesserung um 75 % des Palmoplantar-Psoriasis-Area-Severity-Index (PPPASI) erreicht. Insgesamt verbesserte sich der PPPASI nach 24 Wochen durchschnittlich um 71,6 %. Eine komplette Abheilung zeigte sich bei n  =  2 Patienten nach 24 Wochen. Bis auf lokale Injektionsreaktionen und leichte Infekte wurden keine unerwünschten Wirkungen beobachtet. Die Fallserie ist ein weiterer Beleg für die Wirksamkeit und Verträglichkeit von Ustekinumab in der Therapie der Pustulosis palmoplantaris. Zur Beurteilung der Langzeitwirkung und -sicherheit sowie der Wirksamkeit einer intermittierenden Therapie sind kontrollierte Studiendaten sowie Beobachtungen im Rahmen von Patientenregistern notwendig. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

    17. Glycogen Synthase Kinase-3 Is an Early Determinant in the Differentiation of Pathogenic Th17 Cells

      PubMed Central

      Beurel, Eléonore; Yeh, Wen-I; Michalek, Suzanne M.; Harrington, Laurie E.; Jope, Richard S.

      2011-01-01

      CD4+ T cells are critical for host defense but are also major drivers of immune-mediated diseases. The classical view of Th1 and Th2 subtypes of CD4+ T cells was recently revised by the identification of the Th17 lineage of CD4+ T cells that produce IL-17, which have been found to be critical in the pathogenesis of autoimmune and other diseases. Mechanisms controlling the differentiation of Th17 cells have been well described, but few feasible targets for therapeutically reducing Th17 cells are known. The generation of Th17 cells requires IL-6 and activation of STAT3. During polarization of CD4+ T cells to Th17 cells, we found that inhibition of glycogen synthase kinase-3 (GSK3) blocked IL-6 production, STAT3 activation, and polarization to Th17 cells. Polarization of CD4+ T cells to Th17 cells increased by 10-fold the expression of GSK3β protein levels in Th17 cells, whereas GSK3β was unaltered in regulatory T cells. Diminishing GSK3 activity either pharmacologically or molecularly blocked Th17 cell production, and increasing GSK3 activity promoted polarization to Th17 cells. In vivo inhibition of GSK3 in mice depleted constitutive Th17 cells in intestinal mucosa, blocked Th17 cell generation in the lung after Francisella tularensis infection, and inhibited the increase in spinal cord Th17 cells and disease symptoms in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. These findings identify GSK3 as a critical mediator of Th17 cell production and indicate that GSK3 inhibitors provide a potential therapeutic intervention to control Th17-mediated diseases. PMID:21191064

    18. [Analysis of the 4th generation outer space bred Angelica dahurica by FTIR spectroscopy].

      PubMed

      Zhu, Yan-ying; Wu, Peng-le; Liu, Mei-yi; Wang, Zhi-zhou; Guo, Xi-hua; Guan, Ying

      2012-03-01

      The major components of the 4th generation outer space bred angelica and the ground group were determined and analyzed by Fourier transform infrared spectroscopy (FTIR) and second derivative spectrum, considering the large mutation of the plants with space mutagenesis. The results show that the content of the coumarin (1741 cm(-1)), which is the main active components of the space angelica dahurica increased, and the content of the protein (1 459, 1 419 cm(-1)) and the fat (930 cm(-1)) increased slightly, whereas the content of the starch and the dietary fiber reduced drastically. There are obvious differences between the peak values of the second derivative spectra of the plants, revealing that the outer space angelica dahurica contained amine component at 1 279 cm(-1). Space mutation breeding is favor of breeding angelica with better idiosyncrasy.

    19. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

      PubMed

      Qin, Xia; Guo, Bingshi T; Wan, Bing; Fang, Lei; Lu, Limin; Wu, Lili; Zang, Ying Qin; Zhang, Jingwu Z

      2010-08-01

      Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

    20. The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients.

      PubMed

      Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin

      2016-05-31

      The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence.

    1. Correlation consistent basis sets for actinides. I. The Th and U atoms.

      PubMed

      Peterson, Kirk A

      2015-02-21

      New correlation consistent basis sets based on both pseudopotential (PP) and all-electron Douglas-Kroll-Hess (DKH) Hamiltonians have been developed from double- to quadruple-zeta quality for the actinide atoms thorium and uranium. Sets for valence electron correlation (5f6s6p6d), cc - pV nZ - PP and cc - pV nZ - DK3, as well as outer-core correlation (valence + 5s5p5d), cc - pwCV nZ - PP and cc - pwCV nZ - DK3, are reported (n = D, T, Q). The -PP sets are constructed in conjunction with small-core, 60-electron PPs, while the -DK3 sets utilized the 3rd-order Douglas-Kroll-Hess scalar relativistic Hamiltonian. Both series of basis sets show systematic convergence towards the complete basis set limit, both at the Hartree-Fock and correlated levels of theory, making them amenable to standard basis set extrapolation techniques. To assess the utility of the new basis sets, extensive coupled cluster composite thermochemistry calculations of ThFn (n = 2 - 4), ThO2, and UFn (n = 4 - 6) have been carried out. After accurately accounting for valence and outer-core correlation, spin-orbit coupling, and even Lamb shift effects, the final 298 K atomization enthalpies of ThF4, ThF3, ThF2, and ThO2 are all within their experimental uncertainties. Bond dissociation energies of ThF4 and ThF3, as well as UF6 and UF5, were similarly accurate. The derived enthalpies of formation for these species also showed a very satisfactory agreement with experiment, demonstrating that the new basis sets allow for the use of accurate composite schemes just as in molecular systems composed only of lighter atoms. The differences between the PP and DK3 approaches were found to increase with the change in formal oxidation state on the actinide atom, approaching 5-6 kcal/mol for the atomization enthalpies of ThF4 and ThO2. The DKH3 atomization energy of ThO2 was calculated to be smaller than the DKH2 value by ∼1 kcal/mol.

    2. In vitro Comparative Evaluation of Tensile Bond Strength of 6(th), 7(th) and 8(th) Generation Dentin Bonding Agents.

      PubMed

      Kamble, Suresh S; Kandasamy, Baburajan; Thillaigovindan, Ranjani; Goyal, Nitin Kumar; Talukdar, Pratim; Seal, Mukut

      2015-05-01

      Newer dentin bonding agents were developed to improve the quality of composite restoration and to reduce time consumption in its application. The aim of the present study was to evaluate tensile bond strength of 6(th), 7(th) and 8(th) generation bonding agents by in vitro method. Selected 60 permanent teeth were assigned into 20 in each group (Group I: 6(th) generation bonding agent-Adper SE plus 3M ESPE, Group II: 7(th) generation bonding agent-G-Bond GC Corp Japan and Group III: 8(th) generation dentin adhesives-FuturaBond, DC, Voco, Germany). With high-speed diamond disc, coronal dentin was exposed, and selected dentin bonding agents were applied, followed by composite restoration. All samples were saved in saline for 24 h and tensile bond strength testing was done using a universal testing machine. The obtained data were tabulated and statistically analyzed using ANOVA test. The tensile bond strength readings for 6(th) generation bonding agent was 32.2465, for 7(th) generation was 31.6734, and for 8(th)-generation dentine bonding agent was 34.74431. The highest tensile bond strength was seen in 8(th) generation bonding agent compared to 6(th) and 7(th) generation bonding agents. From the present study it can be conclude that 8(th) generation dentine adhesive (Futura DC, Voco, Germany) resulted in highest tensile bond strength compared to 6(th) (Adper SE plus, 3M ESPE) and 7(th) generation (G-Bond) dentin bonding agents.

    3. Abstracts for the 4th Annual Congress on Medicine & Science in Ultra-Endurance Sports, May 30, 2017, Denver, Colorado.

      PubMed

      2017-04-01

      The 4th Annual Congress on Medicine & Science in Ultra-Endurance Sports will be held on May 30, 2017, in Denver, Colorado. While prior meetings have been multiple-day events, the 2017 Congress will be an intense 1-day preconference to the American College of Sports Medicine annual meeting. Details of this Congress, as well as past and future meetings, can be found at the Ultra Sports Science Foundation Web site: http://ultrasportsscience.us.

    4. Spectroscopic investigations of ThF and ThF+.

      PubMed

      Barker, Beau J; Antonov, Ivan O; Heaven, Michael C; Peterson, Kirk A

      2012-03-14

      The electronic spectra of ThF and ThF(+) have been examined using laser induced fluorescence and resonant two-photon ionization techniques. The results from high-level ab initio calculations have been used to guide the assignment of these data. Spectra for ThF show that the molecule has an X (2)Δ(3/2) ground state. The upper spin-orbit component, X (2)Δ(5/2) was found at an energy of 2575(15) cm(-1). The low-lying states of ThF(+) were probed using dispersed fluorescence and pulsed field ionization-zero kinetic energy (PFI-ZEKE) photoelectron spectroscopy. Vibronic progressions belonging to four electronic states were identified. The lowest energy states were clearly (1)Σ(+) and (3)Δ(1). Although the energy ordering could not be rigorously determined, the evidence favors assignment of (1)Σ(+) as the ground state. The (3)Δ(1) state, of interest for investigation of the electron electric dipole moment, is just 315.0(5) cm(-1) above the ground state. The PFI-ZEKE measurements for ThF yielded an ionization energy of 51 581(3) cm(-1). Molecular constants show that the vibrational constant increases and the bond length shortens on ionization. This is consistent with removal of a non-bonding Th-centered 6d or 7s electron. Laser excitation of ThF(+) was used to probe electronically excited states in the range of 19,000-21,500 cm(-1).

    5. Influence of Skip Patterns on Item Non-Response in a Substance Use Survey of 7th to 12th Grade Students

      ERIC Educational Resources Information Center

      Ding, Kele; Olds, R. Scott; Thombs, Dennis L.

      2009-01-01

      This retrospective case study assessed the influence of item non-response error on subsequent response to questionnaire items assessing adolescent alcohol and marijuana use. Post-hoc analyses were conducted on survey results obtained from 4,371 7th to 12th grade students in Ohio in 2005. A skip pattern design in a conventional questionnaire…

    6. The role of Th1 and Th17 cells in glomerulonephritis.

      PubMed

      Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

      2015-04-01

      T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.

    7. Evidence of human-induced morphodynamic changes along the Campania coastal areas (southern Italy) since the 3rd-4th cent. AD

      NASA Astrophysics Data System (ADS)

      Russo Ermolli, Elda; Romano, Paola; Liuzza, Viviana; Amato, Vincenzo; Ruello, Maria Rosaria; Di Donato, Valentino

      2014-05-01

      Campania has always offered suitable climatic and physiographic conditions for human settlements since prehistoric times. In particular, many Graeco-Roman towns developed along its coasts starting from the 7th-6th cent. BC. In the last decade, geoarchaelogical surveys have been carried out in the archaeological excavations of Neapolis, Paestum and Elea-Velia allowing the main steps of the landscape evolution around these towns to be defined in detail. The greek town of Neapolis rose in the late 6th cent. BC [1] on a terrace overlooking a low-relief rocky coast surrounded by volcanic hills. Port activities developed in a protected bay facing the town from the 4th-2nd cent. BC up to the 4th cent. AD, as testified by the discovery of structures and shipwrecks [2, 3, 4]. Starting from the 3rd cent. AD a spit bar formed at the bay entrance causing the progressive establishment of a lagoon which was gradually filled up by alluvial inputs and completely closed in the 5th cent. AD. During the same period, episodes of increased alluvial inputs were also recorded further west along the coast, where a narrow sandy beach formed at the cliff toe. The greek town of Poseidonia, renamed Paestum by the Romans, was founded in the 540 BC on a travertine terrace facing the sandy littoral of a prograding coastal plain [5]. In front of the main town door, a coastal lagoon developed thanks to the growth of a dune ridge and was probably used for harbor activities [5]. After this period the shoreline shifted seawards, another dune ridge formed and the back-ridge depression was filled with fluvial-marshy deposits, slowly drying up. Phases of travertine deposition, which characterized the SE sector of the plain all along the Holocene, were recorded in the northern and southern quarters of the town in historical times and were connected to the abandonment of the town in the early Medieval times. The greek colony of Elea-Velia was located on top of a siliciclastic promontory where the ruins of

    8. Laser-Ablation (U-Th)/He Geochronology

      NASA Astrophysics Data System (ADS)

      Hodges, K.; Boyce, J.

      2003-12-01

      Over the past decade, ultraviolet laser microprobes have revolutionized the field of 40Ar/39Ar geochronology. They provide unprecedented information about Ar isotopic zoning in natural crystals, permit high-resolution characterization of Ar diffusion profiles produced during laboratory experiments, and enable targeted dating of multiple generations of minerals in thin section. We have modified the analytical protocols used for 40Ar/39Ar laser microanalysis for use in (U-Th)/He geochronologic studies. Part of the success of the 40Ar/39Ar laser microprobe stems from fact that measurements of Ar isotopic ratios alone are sufficient for the calculation of a date. In contrast, the (U-Th)/He method requires separate analysis of U+Th and 4He. Our method employs two separate laser microprobes for this process. A target mineral grain is placed in an ultrahigh vacuum chamber fitted with a window of appropriate composition to transmit ultraviolet radiation. A focused ArF (193 nm) excimer laser is used to ablate tapered cylindrical pits on the surface of the target. The liberated material is scrubbed with a series of getters in a fashion similar to that used for 40Ar/39Ar geochronology, and the 4He abundance is determined using a quadrupole mass spectrometer with well-calibrated sensitivity. A key requirement for calculation of the 4He abundance in the target is a precise knowledge of the volume of the ablation pit. This is the principal reason why we employ the ArF excimer for 4He analysis rather than a less-expensive frequency-multiplied Nd-YAG laser; the excimer creates tapered cylindrical pits with extremely reproducible and easily characterized geometry. After 4He analysis, U and Th are measured on the same sample surface using the more familiar technique of laser-ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Our early experiments have been done using a frequency-quintupled Nd-YAG microprobe (213nm), While the need to analyze U+Th and He in separate

    9. Interaction between U and Th on their uptake, distribution, and toxicity in V S. alfredii based on the phytoremediation of U and Th.

      PubMed

      Huang, Zhenling; Tang, Siqun; Zhang, Lu; Ma, Lijian; Ding, Songdong; Du, Liang; Zhang, Dong; Jin, Yongdong; Wang, Ruibing; Huang, Chao; Xia, Chuanqin

      2017-01-01

      Variant Sedum alfredii Hance (V S. alfredii) could simultaneously take up U and Th from water with the highest concentrations recorded as 1.84 × 10 4 and 6.72 × 10 3  mg/kg in the roots, respectively. Th stimulated U uptake by V S. alfredii roots at Th 10 (10 μM of Th), however, the opposite was observed at Th 100 (100 μM of Th). A similar result was found in the effect of U on the uptake of Th by V S. alfredii. Subcellular fractionation studies of V S. alfredii indicated that U and Th were mainly stored in cell wall fraction, and much less was found in organelle and soluble fractions. Chemical form examination results showed that water-soluble U and Th were the predominant chemical forms in this plant. Addition of the other radionuclide in aqueous solutions altered the concentration and percentage of U or Th in cell wall fraction and in water-soluble form, resulting in the change of the uptake capacity of U or Th by V S. alfredii roots. Comparing with single U or Th treatment, the plant cells revealed more swollen chloroplasts and enhanced thickening in cell walls under the U 100  + Th 100 treatment, as observed by TEM. Those results collectively displayed that V S. alfredii may be utilized as a potential plant to simultaneously remove U and Th from aqueous solutions (rhizofiltration).

    10. [Comments on the seven clinical questions & answers in Japanese gastric treatment guidelines of the 4th edition].

      PubMed

      Xu, J M

      2017-03-23

      Japanese gastric cancer treatment guidelines of the 4th Edition proposed solutions to 7 clinically contentious questions. However, the solutions to question 1-3 are not complete and may cause ambiguity. In order to avoid the wrong choice of surgical resection, the solutions to question 1-3 should be clearly defined. For question 1-3, we suggest provisos be added such as patients with resectable M1 disease and without any other non-curable factors, after whose status and tumor biological behavior being fully understood and being fully discussed by a multidisciplinary team, can be recommended to receive comprehensive treatment including surgical resection.

    11. Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection.

      PubMed

      Licona-Limón, Paula; Henao-Mejia, Jorge; Temann, Angela U; Gagliani, Nicola; Licona-Limón, Ileana; Ishigame, Harumichi; Hao, Liming; Herbert, De'broski R; Flavell, Richard A

      2013-10-17

      Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4⁺ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection. Copyright © 2013 Elsevier Inc. All rights reserved.

    12. The Reich Wreckers: An Analysis of the 306th Bomb Group During World War II

      DTIC Science & Technology

      1998-04-01

      1983), 179-80. 12 Notes 4 Russell A. Strong, First Over Germany : The Story of the 306th Bombardment Group, (Winston-Salem, NC: Hunter Printing Co...306th Bombardment Group (H), GP-306-HI, in USAF Collection, AFHRA, 4. 7 Russell A. Strong, First Over Germany : The Story of the 306th Bombardment...306th Bomb Group Association, 1994), cover. 9 Russell A. Strong, First Over Germany : The Story of the 306th Bombardment Group, (Winston-Salem, NC: Hunter

    13. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

      PubMed

      Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

      2016-01-01

      Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

    14. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161+Th1 Cells) to CD161+Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients

      PubMed Central

      Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

      2016-01-01

      Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase. PMID:27123445

    15. Climatic changes and social transformations in the Near East and North Africa during the 'long' 4th millennium BC: A comparative study of environmental and archaeological evidence

      NASA Astrophysics Data System (ADS)

      Clarke, Joanne; Brooks, Nick; Banning, Edward B.; Bar-Matthews, Miryam; Campbell, Stuart; Clare, Lee; Cremaschi, Mauro; di Lernia, Savino; Drake, Nick; Gallinaro, Marina; Manning, Sturt; Nicoll, Kathleen; Philip, Graham; Rosen, Steve; Schoop, Ulf-Dietrich; Tafuri, Mary Anne; Weninger, Bernhard; Zerboni, Andrea

      2016-03-01

      This paper explores the possible links between rapid climate change (RCC) and social change in the Near East and surrounding regions (Anatolia, central Syria, southern Israel, Mesopotamia, Cyprus and eastern and central Sahara) during the 'long' 4th millennium (∼4500-3000) BC. Twenty terrestrial and 20 marine climate proxies are used to identify long-term trends in humidity involving transitions from humid to arid conditions and vice versa. The frequency distribution of episodes of relative aridity across these records is calculated for the period 6300-2000 BC, so that the results may be interpreted in the context of the established arid episodes associated with RCC around 6200 and 2200 BC (the 8.2 and 4.2 kyr events). We identify two distinct episodes of heightened aridity in the early-mid 4th, and late 4th millennium BC. These episodes cluster strongly at 3600-3700 and 3100-3300 BC. There is also evidence of localised aridity spikes in the 5th and 6th millennia BC. These results are used as context for the interpretation of regional and local archaeological records with a particular focus on case studies from western Syria, the middle Euphrates, southern Israel and Cyprus. Interpretation of the records involves the construction of plausible narratives of human-climate interaction informed by concepts of adaptation and resilience from the literature on contemporary (i.e. 21st century) climate change and adaptation. The results are presented alongside well-documented examples of climatically-influenced societal change in the central and eastern Sahara, where detailed geomorphological studies of ancient environments have been undertaken in tandem with archaeological research. While the narratives for the Near East and Eastern Mediterranean remain somewhat speculative, the use of resilience and adaptation frameworks allows for a more nuanced treatment of human-climate interactions and recognises the diversity and context-specificity of human responses to climatic

    16. CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells.

      PubMed

      Restorick, S M; Durant, L; Kalra, S; Hassan-Smith, G; Rathbone, E; Douglas, M R; Curnow, S J

      2017-08-01

      Considerable attention has been given to CCR6 + IL-17-secreting CD4 + T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6 + cells in MS CSF. Here we identify the dominant CCR6 + T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

    17. dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses

      PubMed Central

      Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

      2017-01-01

      German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma. PMID:28775364

    18. dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

      PubMed

      Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

      2017-08-04

      German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

    19. The 4th annual European League Against Rheumatism congress in Lisbon: a personal perspective

      PubMed Central

      Wollheim, Frank A

      2004-01-01

      The 4th annual European League Against Rheumatism congress, held in Lisbon, 18–21 June 2003, had a record turnout of more than 8600 delegates and the abstract submissions increased to 2600. A heat wave and a somewhat substandard venue hampered some of the activities, notably the poster sessions. The scientific program was comprehensive and of a high class, and it was organized in 10–12 parallel sessions. The European League Against Rheumatism standing committees are expanding their activities and stimulating European cooperation (e.g. by creating databases and guidelines, and by starting research programs). The standing committees presented several areas where European cooperative work is in progress. Advances in drug therapy were a prominent theme and were well presented. Commercialism remains a problem for this meeting as for other similar large meetings, where satellite symposia surround the scientific program of the congress and often duplicate this. PMID:14979931

    20. 4th Stage Transvaginal omental herniation during VBAC complicated by shoulder dystocia: a unique presentation of uterine rupture

      PubMed Central

      2013-01-01

      Background Uterine rupture is a common complication in women attempting their first virginal birth after caesarean section (VBAC) but the risk diminishes with subsequent VBACs. It occurs in rates of 0.5-9% and is influenced by various factors. Case presentation A unique case of uterine rupture in a Kenyan woman of African descent during a repeat VBAC complicated by shoulder dystocia was discovered during the 4th stage of labour when omentum was noted protruding through the vagina. She had delivered 4 years earlier by caesarean section. Conclusion It is not common to experience uterine rupture among women attempting repeat VBAC. When it occurs, it may not always follow the known pattern intra-partum and is often associated with poor foetal outcome. PMID:23521920

    1. 9th Caribbean Geological Conference

      NASA Astrophysics Data System (ADS)

      Draper, Gren

      The ninth in a series of Caribbean Geological Conferences, which are held every 3 or 4 years, took place in Santo Domingo, capital of the Dominican Republic, from the 15th to 26th of August 1980. The conference, which was sponsored by the government of the Dominican Republic and the Universidad Catolica Madre y Maestra, was preceded by 2 days of field trips and was opened by President Antonio Guzman on the evening of the 17th of August. Generous support was provided by Alcoa Exploration Co., Falconbridge Dominicana, and Rosario Dominicana.Geologists and geophysicists from 25 countries presented about 130 papers on a wide variety of topics ranging from geophysics to paleontology. While the whole Caribbean area was discussed, there was special emphasis on the northern Caribbean and Hispaniola, as befitted the site of the conference. The contribution of workers from the Dirección General de Mineriá was particularly notable.

    2. Th9 and other IL-9-producing cells in allergic asthma.

      PubMed

      Koch, Sonja; Sopel, Nina; Finotto, Susetta

      2017-01-01

      Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4 + T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease. Regarding Th9 cells, it is known that naïve T cells develop into IL-9-producing cells in the presence of interleukin-4 (IL-4) and transforming growth factor beta (TGFβ). Downstream of IL-4, several transcription factors like signal transducer and activator of transcription 6 (STAT6), interferon regulatory factor 4 (IRF4), GATA binding protein 3 (GATA3), basic leucine zipper transcription factor, ATF-like (BATF) and nuclear factor of activated T cells (NFAT) are activated. Additionally, the transcription factor PU.1, which is downstream of TGFβ signaling, also seems to be crucial in the development of Th9 cells. IL-9 is a pleiotropic cytokine that influences various distinct functions of different target cells such as T cells, B cells, mast cells and airway epithelial cells by activating STAT1, STAT3 and STAT5. Because of its pleiotropic functions, IL-9 has been demonstrated to be involved in several diseases, such as cancer, autoimmunity and other pathogen-mediated immune-regulated diseases. In this review, we focus on the role of Th9 and IL-9-producing cells in allergic asthma.

    3. The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients

      PubMed Central

      Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin

      2016-01-01

      Objective The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. Methods In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. Results The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Conclusion Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence. PMID:27121425

    4. The imbalance of Th17/Treg in patients with uterine cervical cancer.

      PubMed

      Zhang, Yan; Ma, Daoxin; Zhang, Yong; Tian, Yongju; Wang, Xuping; Qiao, Yunbo; Cui, Baoxia

      2011-05-12

      Th17/Treg was reported to play critical roles in immunoregulation, and its imbalance may lead to autoimmune diseases and allergic reactions. Information on Th17/Treg in cancer bearing hosts is still limited. We examined the expression of IL-17, Foxp3 and IL-10 in uterine cervical cancer (UCC) patients, cervical intraepithelial neoplasia (CIN) patients and healthy controls by flow cytometry and enzyme-linked immunosorbent assay. Interleukin (IL)-17-producing CD4+ cells as Th17 and CD4+CD25+Foxp3+ cells as Treg were expressed as a percentage of the total CD4+ cells. Compared with controls, patients with UCC or CIN had a higher proportion of Th17 cells. UCC patients also revealed a significant increase in Treg number and IL-17 and IL-10 concentrations in plasma, while CIN patients did not. Notably, in UCC patients, the increased Th17 prevalence was associated with clinical stage, lymph node metastases and vasoinvasion, while the increased Treg frequency was associated with tumor differentiation. Remarkably, an attractive imbalance of Th17/Treg was observed in UUC and CIN patients. Furthermore, in UCC patients with lymph node metastases or vasoinvasion, the ratio of Th17/Treg was significantly higher than that in negative patients respectively. Our results indicated a possible role of Th17 in UCC patients correlated to Treg cells, and the imbalance of Th17/Treg may be involved in the development and progression of UCC. Copyright © 2011 Elsevier B.V. All rights reserved.

    5. Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation.

      PubMed

      Fang, Difeng; Cui, Kairong; Hu, Gangqing; Gurram, Rama Krishna; Zhong, Chao; Oler, Andrew J; Yagi, Ryoji; Zhao, Ming; Sharma, Suveena; Liu, Pentao; Sun, Bing; Zhao, Keji; Zhu, Jinfang

      2018-05-07

      GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they colocalize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5, and IL-13, is up-regulated in Bcl11b -deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3 dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

    6. Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells

      PubMed Central

      Bengtsson, Å; Lundberg, M; Avila-Cariño, J; Jacobsson, G; Holmgren, A; Scheynius, A

      2001-01-01

      The thiol antioxidant N-acetyl-l-cysteine (NAC), known as a precursor of glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC are known to enhance T cell proliferation, production of IL-2 and up-regulation of the IL-2 receptor. The 120-kD CD30 surface antigen belongs to the tumour necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper (Th) cells and its expression is sustained in Th2 cells. We have analysed the effect of GSH and NAC on the cytokine profile and CD30 expression on human allergen-specific T cell clones (TCC). TCC were stimulated with anti-CD3 antibodies in the presence of different concentrations of GSH and NAC. Both thiols caused a dose dependent down-regulation of IL-4, IL-5 and IFN-γ levels in Th0 and Th2 clones, with the most pronounced decrease of IL-4. Furthermore, they down-regulated the surface expression of CD30, and the levels of soluble CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface expression of CD28 or CD40 ligand (CD40L) was not significantly changed after treatment with 20 mm NAC. These results indicate that GSH and NAC favour a Th1 response by a preferential down-regulation of IL-4. In addition, the expression of CD30 was down regulated by GSH and NAC, suggesting that CD30 expression is dependent on IL-4, or modified by NAC. In the likely event that CD30 and its soluble counterpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the treatment of these diseases. PMID:11298119

    7. The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses.

      PubMed

      Durán-Aniotz, Claudia; Segal, Gabriela; Salazar, Lorena; Pereda, Cristián; Falcón, Cristián; Tempio, Fabián; Aguilera, Raquel; González, Rodrigo; Pérez, Claudio; Tittarelli, Andrés; Catalán, Diego; Nervi, Bruno; Larrondo, Milton; Salazar-Onfray, Flavio; López, Mercedes N

      2013-04-01

      Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH(+) with respect to DTH(-) unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Healthy donors and melanoma patient's lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4(+) TGF-β(+)) regulatory T lymphocytes compared with healthy donors. Notably, DTH(+) patients showed a threefold reduction of Th3 cells compared with DTH(-) patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH(+) with respect to DTH(-) patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.

    8. High surface area ThO.sub.2 catalyst and method of preparing it

      DOEpatents

      Colmenares, Carlos A.; Somorjai, Gabor A.; Maj, Joseph J.

      1985-01-01

      A ThO.sub.2 catalyst having a high surface area of about 80-125 m.sup.2 /g is synthesized. The compound is synthesized by simultaneously mixing an aqueous solution of ThNO.sub.3 (NO.sub.3).sub.4.4H.sub.2 O with an aqueous solution of Na.sub.2 CO.sub.3.H.sub.2 O, to produce a solution and solid ThOCO.sub.3. The solid ThOCO.sub.3 is separated from the solution, and then calcined at a temperature of about 225.degree.-300.degree. C. for about 40-55 hours to produce ThO.sub.2. The ThO.sub.2 catalyst produced includes Na present as a substitutional cation in an amount equal to about 5-10 atom percent.

    9. The Effect of the Conceptual Change Oriented Instruction through Cooperative Learning on 4th Grade Students' Understanding of Earth and Sky Concepts

      ERIC Educational Resources Information Center

      Celikten, Oksan; Ipekcioglu, Sevgi; Ertepinar, Hamide; Geban, Omer

      2012-01-01

      The purpose of this study was to compare the effectiveness of the conceptual change oriented instruction through cooperative learning (CCICL) and traditional science instruction (TI) on 4th grade students' understanding of earth and sky concepts and their attitudes toward earth and sky concepts. In this study, 56 fourth grade students from the…

    10. Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

      PubMed Central

      Zhou, X; Paulsson, G; Stemme, S; Hansson, G K

      1998-01-01

      Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the

    11. Bullous pemphigoid followed by pustular psoriasis showing Th1, Th2, Treg and Th17 immunological changes.

      PubMed

      Yasukawa, Shinsuke; Dainichi, Teruki; Kokuba, Hisashi; Moroi, Yoichi; Urabe, Kazunori; Hashimoto, Takashi; Furue, Masutaka

      2009-01-01

      Psoriasis vulgaris is occasionally accompanied by autoimmune bullous diseases, but the opposite is very rare. We document here the first reported case of generalized pustular psoriasis that appeared during steroid therapy for bullous pemphigoid. The serum cytokine levels and the results of an immunohistochemical study over the disease course suggest that the immunological state was consistent with a shift from Th2-dominance to Th1-dominance. IL-17-producing cells appeared in the skin lesions when each disease was most exacerbated and disappeared after remission. Thus, the present case demonstrated a dynamic immunological state in which the appearances of Th1 and Th2 as well as Th17 varied during the course of the disease.

    12. Changes of serum cytokines-related Th1/Th2/Th17 concentration in patients with postmenopausal osteoporosis.

      PubMed

      Zhang, Jing; Fu, Qin; Ren, Zhaozhou; Wang, Yanjun; Wang, Chenchen; Shen, Tao; Wang, Guangbin; Wu, Lina

      2015-03-01

      Postmenopausal osteoporosis is now hypothetically considered to be an autoimmune and inflammatory process in which many pro-inflammatory and T cell-derived cytokines play important roles in the loss of bone mass. For instance, interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) secreted by Th1 and IL-6, IL-4, and IL-10 secreted by Th2 have been shown to be involved in the pathogenesis of osteoporosis. Interleukin-17 (IL-17) is a characteristic cytokine secreted by Th17 cells of the CD4 + subgroup. Although IL-17 has been shown to enhance bone resorption in ovariectomized mouse model, bone cells and genetic research, human-related studies of IL-17 are few. According to WHO classification of osteoporosis by the T scores of BMD, the subjects were divided into the postmenopausal osteoporosis group (T scores≤-2.5), the postmenopausal osteopenia group (-2.5 < T scores<-1), and the postmenopausal normal BMD group (T scores≥-1); 30 subjects in each group. Cytometric bead array (CBA) technique was employed for serum determination of the primary indexes including IL-17A, IL-2, IFN-γ, TNF-α, IL-6, IL-4, and IL-10 concentrations in the 90 volunteers. In the meantime, serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were also determined in the patients. One-way analysis of variance (one-way ANOVA) was employed in data analysis to determine whether the testing results of various parameters had significant differences. The bivariate correlation was tested with the Pearson correlation coefficient. When p < 0.05, the difference was considered to have statistical significance. Serum IL-17A concentration was significantly higher in the postmenopausal osteoporosis group than in the postmenopausal osteopenia group and the postmenopausal normal BMD group, but the difference between the postmenopausal osteopenia group and the postmenopausal normal BMD group had no statistical significance. IL-17A was

    13. Correlation consistent basis sets for actinides. I. The Th and U atoms

      DOE Office of Scientific and Technical Information (OSTI.GOV)

      Peterson, Kirk A., E-mail: kipeters@wsu.edu

      New correlation consistent basis sets based on both pseudopotential (PP) and all-electron Douglas-Kroll-Hess (DKH) Hamiltonians have been developed from double- to quadruple-zeta quality for the actinide atoms thorium and uranium. Sets for valence electron correlation (5f6s6p6d), cc − pV nZ − PP and cc − pV nZ − DK3, as well as outer-core correlation (valence + 5s5p5d), cc − pwCV nZ − PP and cc − pwCV nZ − DK3, are reported (n = D, T, Q). The -PP sets are constructed in conjunction with small-core, 60-electron PPs, while the -DK3 sets utilized the 3rd-order Douglas-Kroll-Hess scalar relativistic Hamiltonian. Bothmore » series of basis sets show systematic convergence towards the complete basis set limit, both at the Hartree-Fock and correlated levels of theory, making them amenable to standard basis set extrapolation techniques. To assess the utility of the new basis sets, extensive coupled cluster composite thermochemistry calculations of ThF{sub n} (n = 2 − 4), ThO{sub 2}, and UF{sub n} (n = 4 − 6) have been carried out. After accurately accounting for valence and outer-core correlation, spin-orbit coupling, and even Lamb shift effects, the final 298 K atomization enthalpies of ThF{sub 4}, ThF{sub 3}, ThF{sub 2}, and ThO{sub 2} are all within their experimental uncertainties. Bond dissociation energies of ThF{sub 4} and ThF{sub 3}, as well as UF{sub 6} and UF{sub 5}, were similarly accurate. The derived enthalpies of formation for these species also showed a very satisfactory agreement with experiment, demonstrating that the new basis sets allow for the use of accurate composite schemes just as in molecular systems composed only of lighter atoms. The differences between the PP and DK3 approaches were found to increase with the change in formal oxidation state on the actinide atom, approaching 5-6 kcal/mol for the atomization enthalpies of ThF{sub 4} and ThO{sub 2}. The DKH3 atomization energy of ThO{sub 2} was calculated to be smaller than

    14. Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson's disease (PD): historical overview and future prospects.

      PubMed

      Nagatsu, Toshiharu; Nagatsu, Ikuko

      2016-11-01

      Tyrosine hydroxylase (TH), which was discovered at the National Institutes of Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines (CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of dopamine and noradrenaline in the brain stem, caused by neurodegeneration of dopamine and noradrenaline neurons, are mainly related to non-motor and motor symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1); aromatic L-amino acid decarboxylase (AADC); dopamine β-hydroxylase (DBH); and phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD in postmortem brains from PD patients, patients with CA-related genetic diseases, mice with genetically engineered CA neurons, and animal models of PD. We purified all human CA-synthesizing enzymes, produced their antibodies for immunohistochemistry and immunoassay, and cloned all human genes, especially the human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of TH. This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.

    15. Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling

      PubMed Central

      Kim, Kyu Sik; Pham, Thanh Nhan Nguyen; Jin, Chun-Ji; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

      2011-01-01

      Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. DC might be a potential target for URC. We demonstrate that URC activates human DC as documented by phenotypic and functional maturation, and altered cytokine production. The expression of CD1a, CD38, CD40, CD54, CD80, CD83, CD86, HLA-DR and CCR7 on URC-primed DC was enhanced. The production of IL-12p70 by URC-primed DC was higher than that of lipopolysaccharide (LPS)-primed DC. The production of IL-12p70 by URC-primed DC was inhibited by the anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb), but partially abolished by anti-TLR2 mAb. mRNA coding for TLR2 and TLR4 was expressed in URC-primed DC. URC-primed DC induced the NF-κB transcription factor. Naïve T cells co-cultured with URC-primed DC turned into typical Th1 cells that produced large quantities of IFN-γ depending on IL-12 secretion. URC enhanced the T cell stimulatory capacity in an allo MLR. In the cytotoxic T-lymphocyte assay (CTL) assay, DNA fragmentation assay and 51Cr release on URC-primed DC were more augmented than that of TNF-α-primed DC. DC matured with URC had an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that URC modulates DC function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR4 signaling, and may be used on DC-based vaccine for cancer immunotherapy. PMID:21499439

    16. Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling.

      PubMed

      Kim, Kyu Sik; Pham, Thanh Nhan Nguyen; Jin, Chun-Ji; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

      2011-02-28

      Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. DC might be a potential target for URC. We demonstrate that URC activates human DC as documented by phenotypic and functional maturation, and altered cytokine production. The expression of CD1a, CD38, CD40, CD54, CD80, CD83, CD86, HLA-DR and CCR7 on URC-primed DC was enhanced. The production of IL-12p70 by URC-primed DC was higher than that of lipopolysaccharide (LPS)-primed DC. The production of IL-12p70 by URC-primed DC was inhibited by the anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb), but partially abolished by anti-TLR2 mAb. mRNA coding for TLR2 and TLR4 was expressed in URC-primed DC. URC-primed DC induced the NF-κB transcription factor. Naïve T cells co-cultured with URC-primed DC turned into typical Th1 cells that produced large quantities of IFN-γ depending on IL-12 secretion. URC enhanced the T cell stimulatory capacity in an allo MLR. In the cytotoxic T-lymphocyte assay (CTL) assay, DNA fragmentation assay and (51)Cr release on URC-primed DC were more augmented than that of TNF-α-primed DC. DC matured with URC had an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that URC modulates DC function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR4 signaling, and may be used on DC-based vaccine for cancer immunotherapy.

    17. Interleukin-4 production by Follicular Helper T cells requires the conserved Il4 enhancer HS V

      PubMed Central

      Vijayanand, Pandurangan; Seumois, Grégory; Simpson, Laura J.; Abdul-Wajid, Sarah; Baumjohann, Dirk; Panduro, Marisella; Huang, Xiaozhu; Interlandi, Jeneen; Djuretic, Ivana M.; Brown, Daniel R.; Sharpe, Arlene H.; Rao, Anjana; Ansel, K. Mark

      2012-01-01

      SUMMARY Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that HS V (also known as CNS2), a 3’ enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in Th2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation, and increased accessibility of the Il4 promoter. Thus Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of Th2 mediated allergic diseases. PMID:22326582

    18. [Effects of shoutai pills on expression of Th1/Th2 cytokine in maternal-fetal interface and pregnancy outcome].

      PubMed

      Lai, Maohua; You, Zhaoling; Ma, Hongxia; Lei, Lei; Lu, Fangguo; He, Dongmei; Liu, Huiping; Yin, Sheng

      2010-11-01

      To evaluate its mechanism of inducing the maternal-fetal immune tolerance by studying the effects of Shoutai pills on the expression of Th1/Th2 cytokine and pregnancy in maternal-fetal interface of mice with recurrent spontaneous abortion (RSA). The normal pregnancy and RSA model were respectively induced with CBA/J x BALB/c and CBA/J x DBA/2. The mice with RSA were randomly divided into model group and low, middle and high dose groups of Shoutai pills. The mice were killed in 14 days after administration and embryo resorption rate was counted and their decidual and placental tissues were co-cultured to detect the expressions of IL-4, IL-10, IFN-gamma and TNF-alpha with ELISA. The embryo resorption rate of the model group was significantly higher than the normal pregnancy, middle and high dose groups of Shoutai pills could decreased the embryo resorption rate of the mice with RSA (P < 0.05). All the doses in 3 groups of Shoutai pills could decreased the expression of IFN-gamma and TNF-alpha (P < 0. 05) and there was no obvious difference between normal pregnancy group and all groups of Shoutai pills. Middle and high doses of Shoutai pills could increased the expression of IL-4 and IL-10 (P < 0.05) and there was no obvious differences between normal pregnancy and high dose group of Shoutai pills. The mechanism about Shoutai pills can change Th1 /Th2 cytokine towards Th2 bias, which induced the maternal-fetal immune tolerance.

    19. Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response.

      PubMed

      Choi, Dae Woon; Kwon, Da-Ae; Jung, Sung Keun; See, Hye-Jeong; Jung, Sun Young; Shon, Dong-Hwa; Shin, Hee Soon

      2018-05-26

      Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1β and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.

    20. Intravaginal Chlamydia trachomatis Challenge Infection Elicits TH1 and TH17 Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract Damage

      PubMed Central

      Quispe Calla, Nirk E.; Pavelko, Stephen D.; Cherpes, Thomas L.

      2016-01-01

      While ascension of Chlamydia trachomatis into the upper genital tract of women can cause pelvic inflammatory disease and Fallopian tube damage, most infections elicit no symptoms or overt upper genital tract pathology. Consistent with this asymptomatic clinical presentation, genital C. trachomatis infection of women generates robust TH2 immunity. As an animal model that modeled this response would be invaluable for delineating bacterial pathogenesis and human host defenses, herein we explored if pathogen-specific TH2 immunity is similarly elicited by intravaginal (ivag) infection of mice with oculogenital C. trachomatis serovars. Analogous to clinical infection, ascension of primary C. trachomatis infection into the mouse upper genital tract produced no obvious tissue damage. Clearance of ivag challenge infection was mediated by interferon (IFN)-γ-producing CD4+ T cells, while IFN-γ signaling blockade concomitant with a single ivag challenge promoted tissue damage by enhancing Chlamydia-specific TH17 immunity. Likewise, IFN-γ and IL-17 signaling blockade or CD4+ T cell depletion eliminated the genital pathology produced in untreated controls by multiple ivag challenge infections. Conversely, we were unable to detect formation of pathogen-specific TH2 immunity in C. trachomatis-infected mice. Together, our work revealed C. trachomatis infection of mice generates TH1 and TH17 immune responses that promote pathogen clearance and immunopathological tissue damage. Absence of Chlamydia-specific TH2 immunity in these mice newly highlights the need to identify experimental models of C. trachomatis genital infection that more closely recapitulate the human host response. PMID:27606424

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