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  1. The TIMS Data User's Workshop

    NASA Technical Reports Server (NTRS)

    Kahle, Anne B. (Editor); Abbott, Elsa (Editor)

    1986-01-01

    A workshop was held to bring together all users of data from NASA's airborne Thermal Infrared Multispectral Scanner (TIMS). The purpose was to allow users to compare results, data processing algorithms, and problems encountered; to update the users on the latest instrument changes and idiosyncracies, including distribution of the TIMS investigation guide; to inform the users of the wide range of problems that are currently being tackled by other TIMS investigators; to explore ways to expand the user community; to discuss current areas where more basic research is required; and to discuss the future directions of NASA's thermal infrared remote sensing programs. Also discussed were: geology, land use, archeology; and data processing and noise research.

  2. Interaction of Tim23 with Tim50 Is essential for protein translocation by the mitochondrial TIM23 complex.

    PubMed

    Gevorkyan-Airapetov, Lada; Zohary, Keren; Popov-Celeketic, Dusan; Mapa, Koyeli; Hell, Kai; Neupert, Walter; Azem, Abdussalam; Mokranjac, Dejana

    2009-02-20

    The TIM23 complex is the major translocase of the mitochondrial inner membrane responsible for the import of essentially all matrix proteins and a number of inner membrane proteins. Tim23 and Tim50, two essential proteins of the complex, expose conserved domains into the intermembrane space that interact with each other. Here, we describe in vitro reconstitution of this interaction using recombinantly expressed and purified intermembrane space domains of Tim50 and Tim23. We established two independent methods, chemical cross-linking and surface plasmon resonance, to track their interaction. In addition, we identified mutations in Tim23 that abolish its interaction with Tim50 in vitro. These mutations also destabilized the interaction between the two proteins in vivo, leading to defective import of preproteins via the TIM23 complex and to cell death at higher temperatures. This is the first study to describe the reconstitution of the Tim50-Tim23 interaction in vitro and to identify specific residues of Tim23 that are vital for the interaction with Tim50.

  3. Corner Office: EBSCO's Tim Collins

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2008-01-01

    This article presents an interview with Tim Collins, president of EBSCO Publishing. The amiable Collins put EBSCO Publishing (EP) on the map through a combination of first-rate search and user-friendly interfaces, a long list of strategic acquisitions, and a dedicated, stable staff. Now, the company Collins has nurtured for over two decades ranks…

  4. Tim-3 and Tim-4 as the potential targets for antitumor therapy.

    PubMed

    Cheng, Lin; Ruan, Zhihua

    2015-01-01

    Both Tim-3 and Tim-4 belong to the T-cell immunoglobulin and mucin domain (Tim) gene family, which plays a critical role in immunoregulation. Tim-3 has been suggested as a negative regulator of anti-tumor immunity due to its function on inducing T cells exhaustion in cancer. In addition to its expression on exhausted T cells, Tim-3 also has been reported to up-regulate on nature killer (NK) cells and promote NK cells functionally exhausted in cancer. While Tim-3 selectively expression on most types of leukemia stem cells, it promotes the progression of acute myeloid leukemia. Recently, data from experimental models of tumor discovered that Tim-3 and Tim-4 up-regulation on tumor associated dendritic cells and macrophages attenuated the anti-tumor effects of cancer vaccines and chemotherapy. Moreover, co-blockage of Tim-3 and PD-1, Tim-3 and CD137, Tim-3 and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) could enhance cell-mediated immunity in advanced tumor, and combined treatment with anti-Tim-3 and anti-Tim-4 mAbs further increase the efficacy of cancer vaccines. The therapeutic manipulation of TIM-3 and TIM-4 may provide a novel strategy to improve the clinical efficacy of cancer immunotherapy.

  5. Expression of TIM-3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of rheumatoid arthritis.

    PubMed

    Li, Shufeng; Peng, Dayong; He, Yeteng; Zhang, Hu; Sun, Huaqiang; Shan, Shiying; Song, Yuanlin; Zhang, Shuzhen; Xiao, Hong; Song, Haihan; Zhang, Ming

    2014-10-01

    Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.

  6. Application of TIMS data in stratigraphic analysis

    NASA Technical Reports Server (NTRS)

    Lang, H. R.

    1986-01-01

    An in-progress study demonstrates the utility of Thermal Infrared Multispectral Scanner (TIMS) data for unraveling the stratigraphic sequence of a western interior, North American foreland basin. The TIMS data can be used to determine the stratigraphic distribution of minerals that are diagnostic of specific depositional distribution. The thematic mapper (TM) and TIMS data were acquired in the Wind River/Bighorn area of central Wyoming in November 1982, and July 1983, respectively. Combined image processing, photogeologic, and spectral analysis methods were used to: map strata; construct stratigraphic columns; correlate data; and identify mineralogical facies.

  7. A geologic atlas of TIMS data

    NASA Technical Reports Server (NTRS)

    Abbott, Elsa

    1986-01-01

    In the three years since the first data were taken, it was well demonstrated that the Thermal Infrared Multispectral Scanner (TIMS), properly used, can be a most valuable tool for the geologist. Compilation of the TIMS data into a geological atlas was felt to be useful. Several data sets were extensively studied to establish TIMS as a geologic tool and to explore the optimum enhancement techniques. It was found that a decorrelation stretch of bands 1, 3, and 5 enhance the data to a form that is very useful and this enhancement will be used in the geologic atlas along with an accompanying geologic map and description. Many data sets are well published and familiar to TIMS users, but there are some sets that, for lack of time and funds, were not thoroughly studied or published. A short description of these least studied sets of data is presented. The images presented along with the many previously studied and published TIMS images constitute an enormously useful set of information for the geologist in the 8 to 10 micron range.

  8. HST PSF simulation using Tiny Tim

    NASA Technical Reports Server (NTRS)

    Krist, J. E.

    1992-01-01

    Tiny Tim is a program which simulates Hubble Space Telescope imaging camera PSF's. It is portable (written and distributed in C) and is reasonably fast. It can model the WFPC, WFPC 2, FOC, and COSTAR corrected FOC cameras. In addition to aberrations such as defocus and spherical, it also includes WFPC obscuration shifting, mirror zonal error maps, and jitter. The program has been used at a number of sites for deconvolving HST images. Tiny Tim is available via anonymous ftp on stsci.edu in the directory software/tinytim.

  9. Essential Roles of TIM-1 and TIM-4 Homologs in Adaptive Humoral Immunity in a Zebrafish Model.

    PubMed

    Xu, Xiao-Gang; Hu, Jing-Fang; Ma, Jun-Xia; Nie, Li; Shao, Tong; Xiang, Li-Xin; Shao, Jian-Zhong

    2016-02-15

    TIM-1 and TIM-4 proteins have become increasingly attractive for their critical functions in immune modulation, particularly in CD4(+) Th2 cell activation. Thus, these proteins were hypothesized to regulate adaptive humoral immunity. However, further evidence is needed to validate this hypothesis. This study describes the molecular and functional characteristics of TIM-1 and TIM-4 homologs from a zebrafish (Danio rerio) model (D. rerio TIM [DrTIM]-1 and DrTIM-4). DrTIM-1 and DrTIM-4 were predominantly expressed in CD4(+) T cells and MHC class II(+) APCs under the induction of Ag stimulation. Blockade or knockdown of both DrTIM-1 and DrTIM-4 significantly decreased Ag-specific CD4(+) T cell activation, B cell proliferation, Ab production, and vaccinated immunoprotection against bacterial infection. This result suggests that DrTIM-1 and DrTIM-4 serve as costimulatory molecules required for the full activation of adaptive humoral immunity. DrTIM-1 was detected to be a trafficking protein located in the cytoplasm of CD4(+) T cells. It can translocate onto the cell surface under stimulation by TIM-4-expressing APCs, which might be a precise regulatory strategy for CD4(+) T cells to avoid self-activation before APCs stimulation. Furthermore, a unique alternatively spliced soluble DrTIM-4 variant was identified to exert a negative regulatory effect on the proliferation of CD4(+) T cells. The above findings highlight a novel costimulatory mechanism underlying adaptive immunity. This study enriches the current knowledge on TIM-mediated immunity and provides a cross-species understanding of the evolutionary history of costimulatory systems throughout vertebrate evolution.

  10. The structure of Tim50(164–361) suggests the mechanism by which Tim50 receives mitochondrial presequences

    SciTech Connect

    Li, Jingzhi; Sha, Bingdong

    2015-08-25

    The Tim50 crystal structure indicates that the IMS domain of Tim50 exhibits significant structural plasticity within the putative presequence-binding groove. Mitochondrial preproteins are transported through the translocase of the outer membrane (TOM) complex. Tim50 and Tim23 then transfer preproteins with N-terminal targeting presequences through the intermembrane space (IMS) across the inner membrane. The crystal structure of the IMS domain of Tim50 [Tim50(164–361)] has previously been determined to 1.83 Å resolution. Here, the crystal structure of Tim50(164–361) at 2.67 Å resolution that was crystallized using a different condition is reported. Compared with the previously determined Tim50(164–361) structure, significant conformational changes occur within the protruding β-hairpin of Tim50 and the nearby helix A2. These findings indicate that the IMS domain of Tim50 exhibits significant structural plasticity within the putative presequence-binding groove, which may play important roles in the function of Tim50 as a receptor protein in the TIM complex that interacts with the presequence and multiple other proteins. More interestingly, the crystal packing indicates that helix A1 from the neighboring monomer docks into the putative presequence-binding groove of Tim50(164–361), which may mimic the scenario of Tim50 and the presequence complex. Tim50 may recognize and bind the presequence helix by utilizing the inner side of the protruding β-hairpin through hydrophobic interactions. Therefore, the protruding β-hairpin of Tim50 may play critical roles in receiving the presequence and recruiting Tim23 for subsequent protein translocations.

  11. Intramolecular Disulfide Bond of Tim22 Protein Maintains Integrity of the TIM22 Complex in the Mitochondrial Inner Membrane*

    PubMed Central

    Okamoto, Hiroaki; Miyagawa, Akiko; Shiota, Takuya; Tamura, Yasushi; Endo, Toshiya

    2014-01-01

    Mitochondrial proteins require protein machineries called translocators in the outer and inner membranes for import into and sorting to their destination submitochondrial compartments. Among them, the TIM22 complex mediates insertion of polytopic membrane proteins into the inner membrane, and Tim22 constitutes its central insertion channel. Here we report that the conserved Cys residues of Tim22 form an intramolecular disulfide bond. By comparison of Tim22 Cys → Ser mutants with wild-type Tim22, we show that the disulfide bond of Tim22 stabilizes Tim22 especially at elevated temperature through interactions with Tim18, which are also important for the stability of the TIM22 complex. We also show that lack of the disulfide bond in Tim22 impairs the assembly of TIM22 pathway substrate proteins into the inner membrane especially when the TIM22 complex handles excess amounts of substrate proteins. Our findings provide a new insight into the mechanism of the maintenance of the structural and functional integrity of the TIM22 complex. PMID:24385427

  12. Immune Regulation and Antitumor Effect of TIM-1

    PubMed Central

    Du, Peng; Xiong, Ruihua; Li, Xiaodong; Jiang, Jingting

    2016-01-01

    T cells play an important role in antitumor immunity, and the T cell immunoglobulin domain and the mucin domain protein-1 (TIM-1) on its surface, as a costimulatory molecule, has a strong regulatory effect on T cells. TIM-1 can regulate and enhance type 1 immune response of tumor association. Therefore, TIM-1 costimulatory pathways may be a promising therapeutic target in future tumor immunotherapy. This review describes the immune regulation and antitumor effect of TIM-1. PMID:27413764

  13. Tim Horton Camps: Spotlight on Onondaga Farms.

    ERIC Educational Resources Information Center

    Evanson, Jason

    2003-01-01

    Tim Horton Children's Foundation operates camps for disadvantaged children that build their self-confidence. The newest camp, Onondaga Farms in Ontario, is also a year-round outdoor education center. Its five program streams--environmental education, creative arts, agriculture, adventure, and recreation--all have direct links to Ontario's…

  14. Tim Rollins + K.O.S.

    ERIC Educational Resources Information Center

    Klawans, Stuart

    1990-01-01

    Explains how artist, Tim Rollins, worked with Kids of Survival, a group of secondary school students in the South Bronx area of New York City, to create large scale art works inspired by Franz Kafka's book, "Amerika." Describes scale, materials used, use of contrasts, and inspiration for these artworks. Suggests similar art activities…

  15. TIM-3 Regulates Distinct Functions in Macrophages

    PubMed Central

    Ocaña-Guzman, Ranferi; Torre-Bouscoulet, Luis; Sada-Ovalle, Isabel

    2016-01-01

    The transmembrane protein TIM-3 is a type I protein expressed by sub-types of lymphoid cells, such as lymphocytes Th1, Th17, Tc1, NK, as well as in myeloid cells. Scientific evidence indicates that this molecule acts as a negative regulator of T lymphocyte activation and that its expression is modified in viral infections or autoimmune diseases. In addition to evidence from lymphoid cells, the function of TIM-3 has been investigated in myeloid cells, such as monocytes, macrophages, and dendritic cells (DC), where studies have demonstrated that it can regulate cytokine production, cell activation, and the capture of apoptotic bodies. Despite these advances, the function of TIM-3 in myeloid cells and the molecular mechanisms that this protein regulates are not yet fully understood. This review examines the most recent evidence concerning the function of TIM-3 when expressed in myeloid cells, primarily macrophages, and the potential impact of that function on the field of basic immunology. PMID:27379093

  16. Thermal Infrared Multispectral Scanner (TIMS): An investigator's guide to TIMS data

    NASA Technical Reports Server (NTRS)

    Palluconi, F. D.; Meeks, G. R.

    1985-01-01

    The Thermal Infrared Multispectral Scanner (TIMS) is a NASA aircraft scanner providing six channel spectral capability in the thermal infrared region of the electromagnetic spectrum. Operating in the atmospheric window region (8 to 12 micrometers) with a channel sensitivity of approximately 0.1 C, TIMS may be used whenever an accurate measure of the Earth's surface is needed. A description of this scanner is provided as well as a discussion of data acquisition and reduction.

  17. Plasma soluble Tim-3 emerges as an inhibitor in sepsis: sepsis contrary to membrane Tim-3 on monocytes.

    PubMed

    Ren, F; Li, J; Jiang, X; Xiao, K; Zhang, D; Zhao, Z; Ai, J; Hou, C; Jia, Y; Han, G; Xie, L

    2015-11-01

    Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim-3 was detected by enzyme-linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) - ADAM10 and ADAM17 were assessed. The Tim-3 and HLA-DR on the monocytes decreased with increasing sepsis severity. The sTim-3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA-DR. sTim-3 levels were negatively correlated with IL-12 and TNF-α. ADAM10 and ADAM17, sheddases of Tim-3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim-3 was involved in the development of sepsis. The homeostasis-promoting role of the Tim-3 on the monocytes was disrupted, while the inhibitory role of sTim-3 emerged during sepsis-induced immunosuppression.

  18. Lithologic mapping of silicate rocks using TIMS

    NASA Technical Reports Server (NTRS)

    Gillespie, A. R.

    1986-01-01

    Common rock-forming minerals have thermal infrared spectral features that are measured in the laboratory to infer composition. An airborne Daedalus scanner (TIMS) that collects six channels of thermal infrared radiance data (8 to 12 microns), may be used to measure these same features for rock identification. Previously, false-color composite pictures made from channels 1, 3, and 5 and emittance spectra for small areas on these images were used to make lithologic maps. Central wavelength, standard deviation, and amplitude of normal curves regressed on the emittance spectra are related to compositional information for crystalline igneous silicate rocks. As expected, the central wavelength varies systematically with silica content and with modal quartz content. Standard deviation is less sensitive to compositional changes, but large values may result from mixed admixture of vegetation. Compression of the six TIMS channels to three image channels made from the regressed parameters may be effective in improving geologic mapping from TIMS data, and these synthetic images may form a basis for the remote assessment of rock composition.

  19. Novel insights into Tim-4 function in autoimmune diseases.

    PubMed

    Fang, Xin-Yu; Xu, Wang-Dong; Pan, Hai-Feng; Leng, Rui-Xue; Ye, Dong-Qing

    2015-06-01

    T-cell immunoglobulin domain and mucin domain-4 (Tim-4) was first recognized as a costimulatory molecule regulating T-cell activation. Dysregulation of Tim-4 has been found in some autoimmune conditions, particularly in the immune cells. Recently, Tim-4 was found to be critical for regulating T cells, with the ability of inhibiting naïve CD4(+) T cells and Th17 cells, increasing Th2 cell development. Tim-4 can also enhance T cell expansion via linker for activation of T cells, extracellular signal-regulated kinase (ERK) and Protein kinase B (PKB, also known as Akt) signaling pathways. Moreover, the Tim-4 signaling pathway may affect multiple molecular processes in autoimmune diseases. A number of previous studies have demonstrated that Tim-4 influences chronic autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus. In addition, an association between Tim-4 polymorphisms and susceptibility to several autoimmune diseases have been identified, such as RA. Taken together, recent works have indicated that Tim-4 may represent a novel target for the treatment of autoimmune diseases. In this article, we will discuss the Tim-4 function and the therapeutic potential of modulating the Tim-4 in autoimmune diseases.

  20. TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

    PubMed

    Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

    2017-01-15

    Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope.

  1. Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability

    PubMed Central

    Kang, Yilin; Baker, Michael James; Liem, Michael; Louber, Jade; McKenzie, Matthew; Atukorala, Ishara; Ang, Ching-Seng; Keerthikumar, Shivakumar; Mathivanan, Suresh; Stojanovski, Diana

    2016-01-01

    The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it’s C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms. DOI: http://dx.doi.org/10.7554/eLife.17463.001 PMID:27554484

  2. BOREAS Level-0 TIMS Imagery: Digital Counts in BIL Format

    NASA Technical Reports Server (NTRS)

    Newcomer, Jeffrey A.; Dominquez, Roseanne; Hall, Forrest G. (Editor)

    2000-01-01

    For BOREAS, the TIMS imagery, along with the other remotely sensed images, was collected to provide spatially extensive information over the primary study areas. The level-0 TIMS images cover the time periods of 16-Apr-1994 to 20-Apr-1994 and 06-Sep-1994 to 17-Sep-1994. The images are available in their original uncalibrated format.

  3. Cutting edge: inhibition of T cell activation by TIM-2.

    PubMed

    Knickelbein, Jared E; de Souza, Anjali J; Tosti, Richard; Narayan, Preeti; Kane, Lawrence P

    2006-10-15

    T cell Ig and mucin domain protein 2 (TIM-2) has been shown to regulate T cell activation in vitro and T cell-mediated disease in vivo. However, it is still not clear whether TIM-2 acts mainly to augment T cell function or to inhibit it. We have directly examined the function of TIM-2 in murine and human T cell lines. Our results indicate that expression of TIM-2 significantly impairs the induction of NFAT and AP-1 transcriptional reporters by not only TCR ligation but also by the pharmacological stimuli PMA and ionomycin. This does not appear to be due to a general effect on cell viability, and the block in NFAT activation can be bypassed by expression of activated alleles of Ras or calcineurin, or MEK kinase, in the case of AP-1. Thus, our data are consistent with a model whereby TIM-2 inhibits T cell activation.

  4. Project TIMS (Teaching Integrated Math/Science)

    NASA Technical Reports Server (NTRS)

    Edwards, Leo, Jr.

    1993-01-01

    The goal of this project is to increase the scientific knowledge and appreciation bases and skills of pre-service and in-service middle school teachers, so as to impact positively on teaching, learning, and student retention. This report lists the objectives and summarizes the progress thus far. Included is the working draft of the TIMS (Teaching Integrated Math/Science) curriculum outline. Seven of the eight instructional subject-oriented modules are also included. The modules include informative materials and corresponding questions and educational activities in a textbook format. The subjects included here are the universe and stars; the sun and its place in the universe; our solar system; astronomical instruments and scientific measurements; the moon and eclipses; the earth's atmosphere: its nature and composition; and the earth: directions, time, and seasons. The module not included regards winds and circulation.

  5. Validation of the Glory TIM and a Ground-Based SORCE TIM (Invited)

    NASA Astrophysics Data System (ADS)

    Harber, D.; Heuerman, K.; Kopp, G.

    2010-12-01

    The total solar irradiance (TSI) climate data record is essential for detecting potential long-term solar variability and estimating climate sensitivity to solar forcing. This data record currently relies on measurements from over 10 different spaceborne radiometers. Because differences between instruments exceed the stated individual instrument uncertainties, the data record to date has depended on overlapping measurements to adjust for offsets in order to generate a single continuous record. This technique is only possible with continuous and overlapping measurements. The risk of loss of continuity in this 32-year record drives the need for a strategy that is robust to a loss of continuity via improved absolute accuracies. Such an approach requires instruments with <0.01% uncertainty on an absolute scale. The TSI Radiometer Facility (TRF) was recently created to perform end-to-end irradiance calibrations of TSI instruments at full solar power with accuracies approaching this level. The first such facility in the world, the TRF allows direct irradiance comparisons between a TSI instrument under test and a NIST-calibrated reference cryogenic radiometer viewing the same uniform input light beam in a common vacuum system. The NASA Glory mission’s Total Irradiance Monitor (TIM), a TSI instrument that is planned for launch in 2010 with a design similar to the SORCE TIM, was validated in the TRF in March-April 2010, and a ground-based SORCE TIM has been similarly validated. Results of these inter-comparisons will be presented.

  6. Expression of Tim-1 in primary CNS lymphoma.

    PubMed

    Kishimoto, Wataru; Nishikori, Momoko; Arima, Hiroshi; Miyoshi, Hiroaki; Sasaki, Yuya; Kitawaki, Toshio; Shirakawa, Kotaro; Kato, Takeharu; Imaizumi, Yoshitaka; Ishikawa, Takayuki; Ohno, Hitoshi; Haga, Hironori; Ohshima, Koichi; Takaori-Kondo, Akifumi

    2016-11-01

    Primary central nervous system lymphoma (PCNSL) is a distinct subtype of extranodal lymphoma with aggressive clinical course and poor outcome. As increased IL-10/IL-6 ratio is recognized in the cerebrospinal fluid (CSF) of PCNSL patients, we hypothesized that PCNSL might originate from a population of B cells with high IL-10-producing capacity, an equivalent of "regulatory B cells" in mice. We intended in this study to clarify whether Tim-1, a molecule known as a marker for regulatory B cells in mice, is expressed in PCNSL. By immunohistochemical analysis, Tim-1 was shown to be positive in as high as 54.2% of PCNSL (26 of 58 samples), while it was positive in 19.1% of systemic diffuse large B-cell lymphoma (DLBCL) samples (17 of 89 samples; P < 0.001). Tim-1 expression positively correlated with IL-10 expression in PCNSL (Cramer's V = 0.55, P < 0.001), and forced expression of Tim-1 in a PCNSL cell line resulted in increased IL-10 secretion, suggesting that Tim-1 is functionally linked with IL-10 production in PCNSL. Moreover, soluble Tim-1 was detectable in the CSF of PCNSL patients, and was suggested to parallel disease activity. In summary, PCNSL is characterized by frequent Tim-1 expression, and its soluble form in CSF may become a useful biomarker for PCNSL.

  7. TIM-1 signaling in B cells regulates antibody production

    SciTech Connect

    Ma, Juan; Usui, Yoshihiko; Takeda, Kazuyoshi; Harada, Norihiro; Yagita, Hideo; Okumura, Ko; Akiba, Hisaya

    2011-03-11

    Highlights: {yields} TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. {yields} Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. {yields} TIM-1 signaling regulates Ab production by response to TI-2 and TD antigens in vivo. -- Abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressed on B cells and inducible on anti-CD3{sup +} anti-CD28-stimulated CD4{sup +} T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.

  8. WFPC2 photometry from subtraction of TinyTim PSFs

    NASA Technical Reports Server (NTRS)

    Remy, M.; Surdej, J.; Baggett, S.; Wiggs, M.

    1997-01-01

    Based upon the subtraction of TinyTim Point Spread Function (PSFs) from Principle Component Image (PC1) point-like objects, a method has been developed to determine the optimal values for the telescope jitter and the Z4 relative focus during calibration or science observations. Using these jitter and focus values, an optimal TinyTim PSF, computed over a resampled grid, is then iteratively fitted to the object, yielding an improvement in the PSF centering, more accurate photometric results and a better detection of underlying structures. Preliminary results seem to indicate that appropriate synthetic TinyTim PSFs perform as well as observed PSFs.

  9. Meet EPA Scientist Tim Shafer, Ph.D.

    EPA Pesticide Factsheets

    Tim Shafer earned his bachelor’s degree in biology and chemistry from Hope College in Holland, MI, in 1986 and his Ph.D. in pharmacology and environmental toxicology from Michigan State University in 1991.

  10. ISS Update: NBL Orion Flight Lead Tim Goddard

    NASA Video Gallery

    NASA Public Affairs Officer Brandi Dean talks with Tim Goddard, Neutral Buoyancy Laboratory (NBL) Orion Flight Lead, about how the NBL is used to train rescue and recovery personnel for future Orio...

  11. 27. YCC CREW THAT REBUILT PIMA POINT TRAILS. TIM BEALE, ...

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

    27. YCC CREW THAT REBUILT PIMA POINT TRAILS. TIM BEALE, NPS TRAILS, FRONT ROW RIGHT; BERNIE PONYAH, NPS YCC SUPERVISOR, BACK ROW RIGHT. - West Rim Drive, Between Grand Canyon Village & Hermit Rest, Grand Canyon, Coconino County, AZ

  12. Targeting Tim-1 to Circumvent Immune Tolerance in Prostate Cancer

    DTIC Science & Technology

    2011-07-01

    Tim-1. We additionally demonstrate that its effect is maintained in humanized HLA- A2.1 transgenic mice when these mice are immunized with peptides ...evidence that manipulating Tim1 with an agonist antibody at time of vaccination strengthens cytotoxic responses to mouse and human prostate tumor...in clinical tria ls that robust anti-tum or immune responses can be generated throug h vaccination , and that inhibitory immune checkpoint receptors

  13. TIM29 is a subunit of the human carrier translocase required for protein transport.

    PubMed

    Callegari, Sylvie; Richter, Frank; Chojnacka, Katarzyna; Jans, Daniel C; Lorenzi, Isotta; Pacheu-Grau, David; Jakobs, Stefan; Lenz, Christof; Urlaub, Henning; Dudek, Jan; Chacinska, Agnieszka; Rehling, Peter

    2016-12-01

    Hydrophobic inner mitochondrial membrane proteins with internal targeting signals, such as the metabolite carriers, use the carrier translocase (TIM22 complex) for transport into the inner membrane. Defects in this transport pathway have been associated with neurodegenerative disorders. While the TIM22 complex is well studied in baker's yeast, very little is known about the mammalian TIM22 complex. Using immunoprecipitation, we purified the human carrier translocase and identified a mitochondrial inner membrane protein TIM29 as a novel component, specific to metazoa. We show that TIM29 is a constituent of the 440 kDa TIM22 complex and interacts with oxidized TIM22. Our analyses demonstrate that TIM29 is required for the structural integrity of the TIM22 complex and for import of substrate proteins by the carrier translocase.

  14. Analysis of TIMS performance subjected to simulated wind blast

    NASA Technical Reports Server (NTRS)

    Jaggi, S.; Kuo, S.

    1992-01-01

    The results of the performance of the Thermal Infrared Multispectral Scanner (TIMS) when it is subjected to various wind conditions in the laboratory are described. Various wind conditions were simulated using a 24 inch fan or combinations of air jet streams blowing toward either or both of the blackbody surfaces. The fan was used to simulate a large volume of air flow at moderate speeds (up to 30 mph). The small diameter air jets were used to probe TIMS system response in reaction to localized wind perturbations. The maximum nozzle speed of the air jet was 60 mph. A range of wind directions and speeds were set up in the laboratory during the test. The majority of the wind tests were conducted under ambient conditions with the room temperature fluctuating no more than 2 C. The temperature of the high speed air jet was determined to be within 1 C of the room temperature. TIMS response was recorded on analog tape. Additional thermistor readouts of the blackbody temperatures and thermocouple readout of the ambient temperature were recorded manually to be compared with the housekeeping data recorded on the tape. Additional tests were conducted under conditions of elevated and cooled room temperatures. The room temperature was varied between 19.5 to 25.5 C in these tests. The calibration parameters needed for quantitative analysis of TIMS data were first plotted on a scanline-by-scanline basis. These parameters are the low and high blackbody temperature readings as recorded by the TIMS and their corresponding digitized count values. Using these values, the system transfer equations were calculated. This equation allows us to compute the flux for any video count by computing the slope and intercept of the straight line that relates the flux to the digital count. The actual video of the target (the lab floor in this case) was then compared with a simulated target. This simulated target was assumed to be a blackbody at emissivity of .95 degrees and the temperature was

  15. The regulation of TIM-3 transcription in T cells involves c-Jun binding but not CpG methylation at the TIM-3 promoter.

    PubMed

    Yun, Su Jin; Jun, Ka-Jung; Komori, Kuniharu; Lee, Mi Jin; Kwon, Myung-Hee; Chwae, Yong-Joon; Kim, Kyongmin; Shin, Ho-Joon; Park, Sun

    2016-07-01

    Tim-3 is an immunomodulatory protein that is expressed constitutively on monocytes but is induced in activated T cells. The mechanisms involved in the regulation of TIM-3 transcription are poorly understood. In the present study, we investigated whether methylation of the TIM-3 promoter is involved in regulatingTIM-3 transcription in T cells, and identified a transcription factor that regulates TIM-3 transcription by associating with the TIM-3 minimal promoter region. Pyrosequencing of the TIM-3 promoter up to -1440bp revealed 11 hypermethylated CpG sites and 4 hypomethylated CpG sites in human CD4(+) T cells as well as in CD11b(+) cells. Dimethylation of histone H3 lysine 4 (H3K4), a mark of transcriptional activation, was predominantly found in the proximal TIM-3 promoter -954 to -34bp region, whereas trimethylation of H3K9 and H3K27, which are markers of transcriptional suppression, were mostly observed in the distal promoter -1549 to -1048bp region in human CD4(+) T cells and CD11b(+) cells. However, no change in the methylation status of CpG sites and the histone H3 in the TIM-3 promoter was found during induction of TIM-3 transcription in T cells. Finally, AP-1 involvement in TIM-3 transcription was shown in relation with the TIM-3 minimal promoter -146 to +144bp region. The present study defines the minimal TIM-3 promoter region and demonstrates its interaction with c-Jun during TIM-3 transcription in CD4(+) T cells.

  16. Up-regulation of Tim-3 is associated with poor prognosis of patients with colon cancer.

    PubMed

    Zhou, Encheng; Huang, Qing; Wang, Ji; Fang, Chengfeng; Yang, Leilei; Zhu, Min; Chen, Jianhui; Chen, Lihua; Dong, Milian

    2015-01-01

    Tim-3 (T cell immunoglobulin and mucin domain 3), belonging to the member of the novel Tim family, has been confirmed that it plays a critical negative role in regulating the immune responses against viral infection and carcinoma. Recently, it has also been reported that the over-expression of Tim-3 is associated with poor prognosis in solid tumors. However, the role of Tim-3 in colorectal cancer remains largely unknown. In the current study, we aim to investigate the expression of Tim-3 in colorectal carcinoma and discuss the relationship between Tim-3 expression and colon cancer prognosis, thus speculating the possible role of Tim-3 in colon cancer progression. Colon cancer tissues and paired normal tissue were obtained from 201 patients with colon cancer for preparation of tissue microarray. Tim-3 expression was evaluated by immunohistochemical staining. The Tim-3 expression level was evaluated by q-RT-PCR, western blot and immunocytochemistry in four colon cancer cell lines (HT-29, HCT116, LoVo, SW620). Tim-3 was expressed in 92.5% tumor tissue samples and 86.5% corresponding normal tissue samples. Expression of Tim-3 was significantly higher in tumor tissues than in normal tissues (P < 0.0001). Tim-3 expression in colon cancer tissues is in correlation with colon cancer lymphatic metastasis and TNM (P < 0.0001). Multivariate analysis demonstrated that Tim-3 expression could be a potential independent prognostic factor for colon cancer patients (P < 0.0001). Kaplan-Meier survival analysis result showed that patients with higher Tim-3 expression had a significantly shorter survival time than those with lower Tim-3 expression patients. Our results indicated that Tim-3 might participate in the tumorgenesis of colon cancer and Tim-3 expression might be a potential independent prognostic factor for patients with colorectal cancer.

  17. Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer.

    PubMed

    Kang, Chiao-Wen; Dutta, Avijit; Chang, Li-Yuan; Mahalingam, Jayashri; Lin, Yung-Chang; Chiang, Jy-Ming; Hsu, Chen-Yu; Huang, Ching-Tai; Su, Wan-Ting; Chu, Yu-Yi; Lin, Chun-Yen

    2015-10-23

    TIM-3 functions to enforce CD8+ T cell exhaustion, a dysfunctional state associated with the tolerization of tumor microenvironment. Here we report apoptosis of IFN-γ competent TIM-3+ population of tumor-infiltrating CD8+ T cells in colon cancer. In humans suffering from colorectal cancer, TIM-3+ population is higher in cancer tissue-resident relative to peripheral blood CD8+ T cells. Both the TIM-3+ and TIM-3- cancer tissue-resident CD8+ T cells secrete IFN-γ of comparable levels, although apoptotic cells are more in TIM-3+ compared to TIM-3- population. In mouse CT26 colon tumor model, majority of tumor-infiltrating CD8+ T cells express TIM-3 and execute cytolysis function with higher effector cytokine secretion and apoptosis in TIM-3+ compared to TIM-3- population. The tumor cells secrete galectin-9, which increases apoptosis of tumor-infiltrating CD8+ T cells. Galectin-9/TIM-3 signaling blockade with anti-TIM-3 antibody reduces the apoptosis and in addition, inhibits tumor growth in mice. The blockade increases therapeutic efficacy of cyclophosphamide to treat tumor in mice as well. These results reveal a previously unexplored role of TIM-3 on tumor-infiltrating CD8+ T cells in vivo.

  18. Activation of TIM1 induces colon cancer cell apoptosis via modulating Fas ligand expression.

    PubMed

    Wang, Hao; Zhang, Xueyan; Sun, Wenjing; Hu, Xiaocui; Li, Xiaolin; Fu, Songbin; Liu, Chen

    2016-04-29

    The pathogenesis of colon cancer is unclear. It is proposed that TIM1 has an association with human cancer. The present study aims to investigate the role of TIM1 activation in the inhibition of human colon cancer cells. In this study, human colon cancer cell line, HT29 and T84 cells were cultured. The expression of TIM1 was assessed by real time RT-PCR and Western blotting. The TIM1 on the cancer cells was activated in the culture by adding recombinant TIM4. The chromatin structure at the FasL promoter locus was assessed by chromatin immunoprecipitation. The apoptosis of the cancer cells was assessed by flow cytometry. The results showed that human colon cancer cell lines, HT29 cells and T84 cells, expressed TIM1. Activation of TIM1 by exposing the cells to TIM4 significantly increased the frequency of apoptotic colon cancer cells. The expression of FasL was increased in the cancer cells after treating by TIM4. Blocking Fas or FasL abolished the exposure to TIM4-induced T84 cell apoptosis. In conclusion, HT29 cells and T84 cells express TIM1; activation TIM1 can induce the cancer cell apoptosis. TIM1 may be a novel therapeutic target of colon cancer.

  19. TIM Version 3.0 beta - Technical Description and User's Guidance

    EPA Pesticide Factsheets

    Provides technical information on version 3.0 of the Terrestrial Investigation Model (TIM v.3.0). Describes how TIM derives joint distributions of exposure and toxicity to calculate the risk of mortality to birds.

  20. Wise Leadership for Student Success: An Interview with Tim White

    ERIC Educational Resources Information Center

    Kezar, Adrianna

    2015-01-01

    Adrianna Kezar recently sat down with Chancellor Tim White of the California State University system to discuss, among many other things, the newly released California State Graduation Initiative and what it will take to enact it. The key commitments of the initiative are: (1) hire more tenure-track faculty; (2) develop engaged advising; (3) solve…

  1. TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection.

    PubMed

    Jayaraman, Pushpa; Jacques, Miye K; Zhu, Chen; Steblenko, Katherine M; Stowell, Britni L; Madi, Asaf; Anderson, Ana C; Kuchroo, Vijay K; Behar, Samuel M

    2016-03-01

    While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis.

  2. Association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with multiple sclerosis in Isfahan population.

    PubMed

    Mazrouei, F; Ganjalikhani-Hakemi, M; Salehi, R; Alesahebfosoul, F; Etemadifar, M; Pouladian, M; Meshkat, R; Nekoueian, Sh; Zarkesh-Esfahani, H; Ziyaee-Ghahnaviyeh, M

    2016-06-01

    Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system, affecting about 2.5 million people around the world. Probable involvement of two newly identified immunoregulator molecules, TIM-1 and TIM-3, has been reported in autoimmune diseases. In this study, for the first time, the association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with MS in an Iranian population was considered. The results of our study showed that there is no significant association between TIM-1 5383-5397ins/del and MS (P = 0.38); however, the frequency of CT genotype of TIM-3 -1541C>T in patient group was significantly higher than the control group, and there was a significant association between CT genotype and MS (P = 0.009, OR = 4.08).

  3. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma.

    PubMed

    Xu, Liyun; Huang, Yanyan; Tan, Linlin; Yu, Wei; Chen, Dongdong; Lu, ChangChang; He, Jianying; Wu, Guoqing; Liu, Xiaoguang; Zhang, Yongkui

    2015-12-01

    T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56+ cells (P<0.05) and CD3-CD56(dim) cells (P<0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P<0.05) or with tumor stage T3-T4 (P<0.05). Tim-3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size ≥3cm (P<0.05), or LNM (P<0.05) or with tumor stage T3-T4 (P<0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56+ NK cells and CD56(dim) NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P=0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-γ production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy.

  4. DNA demethylation of the TIM-3 promoter is critical for its stable expression on T cells.

    PubMed

    Chou, F-C; Kuo, C-C; Chen, H-Y; Chen, H-H; Sytwu, H-K

    2016-04-01

    The T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is selectively expressed on terminally differentiated T helper 1 (Th1) cells and acts as a negative regulator that terminates Th1 responses. The dysregulation of TIM-3 expression on T cells is associated with several autoimmune phenotypes and with chronic viral infections; however, the mechanism of this regulation is unclear. In this study, we investigated the effect of DNA methylation on the expression of TIM-3. By analyzing the sequences of TIM-3 promoter regions in human and mouse, we identified a CpG island within the TIM-3 promoter and demonstrated that the promoter activity was controlled by DNA methylation. Furthermore, treatment with 5-aza-2'-deoxycytidine enhanced TIM-3 expression on mouse primary CD4(+) T cells under Th0-, Th1- or Th2-polarizing conditions. Finally, pyrosequencing analysis revealed that the methylation level of the TIM-3 promoter gradually decreased after each round of T-cell polarization, and this decrease was inversely correlated with TIM-3 expression. These data suggest that the DNA methylation of the TIM-3 promoter cooperates with lineage-specific transcription factors in the control of Th-cell development. In conclusion, DNA methylation-based regulation of TIM-3 may provide novel insights into understanding the dysregulation of TIM-3 expression under pathogenic conditions.

  5. Preliminary crystallographic studies of yeast mitochondrial peripheral membrane protein Tim44p

    SciTech Connect

    Josyula, Ratnakar; Jin, Zhongmin; McCombs, Deborah; DeLucas, Lawrence; Sha, Bingdong

    2006-02-01

    Tim44p is an essential mitochondrial peripheral membrane protein. To investigate the mechanism by which Tim44p functions in the TIM23 translocon to deliver the mitochondrial protein precursors, the yeast Tim44p has been crystallized. Protein translocations across mitochondrial membranes play critical roles in mitochondrion biogenesis. Protein transport from the cell cytosol to the mitochondrial matrix is carried out by the translocase of the outer membrane (TOM) complex and the translocase of the inner membrane (TIM) complexes. Tim44p is an essential mitochondrial peripheral membrane protein and a major component of the TIM23 translocon. To investigate the mechanism by which Tim44p functions in the TIM23 translocon to deliver the mitochondrial protein precursors, the yeast Tim44p was crystallized. The crystals diffract to 3.2 Å using a synchrotron X-ray source and belong to space group P6{sub 3}22, with unit-cell parameters a = 124.25, c = 77.83 Å. There is one Tim44p molecule in one asymmetric unit, which corresponds to a solvent content of approximately 43%. Structure determination by MAD methods is under way.

  6. Inspiring pupils in STEM through Tim Peake's Principia Mission

    NASA Astrophysics Data System (ADS)

    Grant, Stephanie

    2016-04-01

    This poster looks at a particular case study of how a science programme with a lot of media attention can be embedded into schools to inspire pupils in STEM subjects. In this case, the UK has become very excited about their first publicly funded British astronaut, Tim Peake, visiting the International Space Station between December 2015 and June 2016. Tim is particularly keen to dedicate a lot of his time to education initiatives including undertaking a live radio contact with a handful of UK schools so that pupils can ask him their questions. A group of schools in Norfolk have won this opportunity and will host a live radio contact in February 2015. As part of this initiative, local schools (primary and secondary) are being encouraged to embed the mission into their curriculum in various ways using many excellent resources developed by a number of agencies. The range of these and our proposed methods for judging their efficacies are explored in this poster.

  7. Techniques for noise removal and registration of TIMS data

    USGS Publications Warehouse

    Hummer-Miller, S.

    1990-01-01

    Extracting subtle differences from highly correlated thermal infrared aircraft data is possible with appropriate noise filters, constructed and applied in the spatial frequency domain. This paper discusses a heuristic approach to designing noise filters for removing high- and low-spatial frequency striping and banding. Techniques for registering thermal infrared aircraft data to a topographic base using Thematic Mapper data are presented. The noise removal and registration techniques are applied to TIMS thermal infrared aircraft data. -Author

  8. Application of split window technique to TIMS data

    NASA Technical Reports Server (NTRS)

    Matsunaga, Tsuneo; Rokugawa, Shuichi; Ishii, Yoshinori

    1992-01-01

    Absorptions by the atmosphere in thermal infrared region are mainly due to water vapor, carbon dioxide, and ozone. As the content of water vapor in the atmosphere greatly changes according to weather conditions, it is important to know its amount between the sensor and the ground for atmospheric corrections of thermal Infrared Multispectral Scanner (TIMS) data (i.e. radiosonde). On the other hand, various atmospheric correction techniques were already developed for sea surface temperature estimations from satellites. Among such techniques, Split Window technique, now widely used for AVHRR (Advanced Very High Resolution Radiometer), uses no radiosonde or any kind of supplementary data but a difference between observed brightness temperatures in two channels for estimating atmospheric effects. Applications of Split Window technique to TIMS data are discussed because availability of atmospheric profile data is not clear when ASTER operates. After these theoretical discussions, the technique is experimentally applied to TIMS data at three ground targets and results are compared with atmospherically corrected data using LOWTRAN 7 with radiosonde data.

  9. Dr TIM: Ray-tracer TIM, with additional specialist scientific capabilities

    NASA Astrophysics Data System (ADS)

    Oxburgh, Stephen; Tyc, Tomáš; Courtial, Johannes

    2014-03-01

    We describe several extensions to TIM, a raytracing program for ray-optics research. These include relativistic raytracing; simulation of the external appearance of Eaton lenses, Luneburg lenses and generalised focusing gradient-index lens (GGRIN) lenses, which are types of perfect imaging devices; raytracing through interfaces between spaces with different optical metrics; and refraction with generalised confocal lenslet arrays, which are particularly versatile METATOYs. Catalogue identifier: AEKY_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKY_v2_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licencing provisions: GNU General Public License No. of lines in distributed program, including test data, etc.: 106905 No. of bytes in distributed program, including test data, etc.: 6327715 Distribution format: tar.gz Programming language: Java. Computer: Any computer capable of running the Java Virtual Machine (JVM) 1.6. Operating system: Any, developed under Mac OS X Version 10.6 and 10.8.3. RAM: Typically 130 MB (interactive version running under Mac OS X Version 10.8.3) Classification: 14, 18. Catalogue identifier of previous version: AEKY_v1_0 Journal reference of previous version: Comput. Phys. Comm. 183(2012)711 External routines: JAMA [1] (source code included) Does the new version supersede the previous version?: Yes Nature of problem: Visualisation of scenes that include scene objects that create wave-optically forbidden light-ray fields. Solution method: Ray tracing. Reasons for new version: Significant extension of the capabilities (see Summary of revisions), as demanded by our research. Summary of revisions: Added capabilities include the simulation of different types of camera moving at relativistic speeds relative to the scene; visualisation of the external appearance of generalised focusing gradient-index (GGRIN) lenses, including Maxwell fisheye, Eaton and Luneburg lenses; calculation of

  10. TIM-4 is expressed on invariant NKT cells but dispensable for their development and function.

    PubMed

    Zhang, Xilin; Gu, Jun; Zhou, Li; Mi, Qing-Sheng

    2016-11-01

    T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes. Using TIM-4-deficient mice, we found that lack of TIM-4 did not disturb iNKT cell development, maturation, peripheral homeostasis and cytokine secretion. Moreover, TIM-4 deficiency did not alter the polarization of iNKT sublineages, including NKT1, NKT2 and NKT17. Finally, the mixed bone marrow transfer experiments further confirmed normal iNKT cell development and function from TIM-4-deficient bone marrow. In conclusion, our data suggest that TIM-4 is expressed on iNKT cells but dispensable for their development and function.

  11. TIM-1 signaling is required for maintenance and induction of regulatory B cells.

    PubMed

    Yeung, M Y; Ding, Q; Brooks, C R; Xiao, S; Workman, C J; Vignali, D A A; Ueno, T; Padera, R F; Kuchroo, V K; Najafian, N; Rothstein, D M

    2015-04-01

    Apart from their role in humoral immunity, B cells can exhibit IL-10-dependent regulatory activity (Bregs). These regulatory subpopulations have been shown to inhibit inflammation and allograft rejection. However, our understanding of Bregs has been hampered by their rarity, lack of a specific marker, and poor insight into their induction and maintenance. We previously demonstrated that T cell immunoglobulin mucin domain-1 (TIM-1) identifies over 70% of IL-10-producing B cells, irrespective of other markers. We now show that TIM-1 is the primary receptor responsible for Breg induction by apoptotic cells (ACs). However, B cells that express a mutant form of TIM-1 lacking the mucin domain (TIM-1(Δmucin) ) exhibit decreased phosphatidylserine binding and are unable to produce IL-10 in response to ACs or by specific ligation with anti-TIM-1. TIM-1(Δmucin) mice also exhibit accelerated allograft rejection, which appears to be due in part to their defect in both baseline and induced IL-10(+) Bregs, since a single transfer of WT TIM-1(+) B cells can restore long-term graft survival. These data suggest that TIM-1 signaling plays a direct role in Breg maintenance and induction both under physiological conditions (in response to ACs) and in response to therapy through TIM-1 ligation. Moreover, they directly demonstrate that the mucin domain regulates TIM-1 signaling.

  12. TIM-4 is expressed on invariant NKT cells but dispensable for their development and function

    PubMed Central

    Zhang, Xilin; Gu, Jun; Zhou, Li; Mi, Qing-Sheng

    2016-01-01

    T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes. Using TIM-4-deficient mice, we found that lack of TIM-4 did not disturb iNKT cell development, maturation, peripheral homeostasis and cytokine secretion. Moreover, TIM-4 deficiency did not alter the polarization of iNKT sublineages, including NKT1, NKT2 and NKT17. Finally, the mixed bone marrow transfer experiments further confirmed normal iNKT cell development and function from TIM-4-deficient bone marrow. In conclusion, our data suggest that TIM-4 is expressed on iNKT cells but dispensable for their development and function. PMID:27662666

  13. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9

    SciTech Connect

    Weyer, Philipp S. van de; Muehlfeit, Michael; Klose, Christoph; Bonventre, Joseph V.; Walz, Gerd; Kuehn, E. Wolfgang . E-mail: wolfgang.kuehn@uniklinik-freiburg.de

    2006-12-15

    Tim-3 is a member of the TIM family of proteins (T-cell immunoglobulin mucin) involved in the regulation of CD4+ T-cells. Tim-3 is a T{sub H}1-specific type 1 membrane protein and regulates T{sub H}1 proliferation and the development of tolerance. Binding of galectin-9 to the extracellular domain of Tim-3 results in apoptosis of T{sub H}1 cells, but the intracellular pathways involved in the regulatory function of Tim-3 are unknown. Unlike Tim-1, which is expressed in renal epithelia and cancer, Tim-3 has not been described in cells other than neuronal or T-cells. Using RT-PCR we demonstrate that Tim-3 is expressed in malignant and non-malignant epithelial tissues. We have cloned Tim-3 from an immortalized liver cell carcinoma line and identified a highly conserved tyrosine in the intracellular tail of Tim-3 (Y265). We demonstrate that Y265 is specifically phosphorylated in vivo by the interleukin inducible T cell kinase (ITK), a kinase which is located in close proximity of the TIM genes on the allergy susceptibility locus 5q33.3. Stimulation of Tim-3 by its ligand galectin-9 results in increased phosphorylation of Y265, suggesting that this tyrosine residue plays an important role in downstream signalling events regulating T-cell fate. Given the role of TIM proteins in autoimmunity and cancer, the conserved SH2 binding domain surrounding Y265 could represent a possible target site for pharmacological intervention.

  14. The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells

    PubMed Central

    Gonçalves Silva, Isabel; Rüegg, Laura; Gibbs, Bernhard F.; Bardelli, Marco; Fruehwirth, Alexander; Varani, Luca; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

    2016-01-01

    ABSTRACT The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells. PMID:27622049

  15. The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells.

    PubMed

    Gonçalves Silva, Isabel; Rüegg, Laura; Gibbs, Bernhard F; Bardelli, Marco; Fruehwirth, Alexander; Varani, Luca; Berger, Steffen M; Fasler-Kan, Elizaveta; Sumbayev, Vadim V

    2016-07-01

    The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells.

  16. Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria.

    PubMed

    Mokranjac, Dejana; Sichting, Martin; Popov-Celeketić, Dusan; Mapa, Koyeli; Gevorkyan-Airapetov, Lada; Zohary, Keren; Hell, Kai; Azem, Abdussalam; Neupert, Walter

    2009-03-01

    Transport of essentially all matrix and a number of inner membrane proteins is governed, entirely or in part, by N-terminal presequences and requires a coordinated action of the translocases of outer and inner mitochondrial membranes (TOM and TIM23 complexes). Here, we have analyzed Tim50, a subunit of the TIM23 complex that is implicated in transfer of precursors from TOM to TIM23. Tim50 is recruited to the TIM23 complex via Tim23 in an interaction that is essentially independent of the rest of the translocase. We find Tim50 in close proximity to the intermembrane space side of the TOM complex where it recognizes both types of TIM23 substrates, those that are to be transported into the matrix and those destined to the inner membrane, suggesting that Tim50 recognizes presequences. This function of Tim50 depends on its association with TIM23. We conclude that the efficient transfer of precursors between TOM and TIM23 complexes requires the concerted action of Tim50 with Tim23.

  17. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms as possible risk factor for rheumatoid arthritis: relation to activity and severity.

    PubMed

    Mosaad, Y M; El-Bassiony, S R; El-Ghaweet, A E; Elhindawy, M M; El-Deek, B S; Sultan, W A

    2015-08-01

    This study was aimed to evaluate the impact of both TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 polymorphisms on susceptibility to rheumatoid arthritis (RA) in a cohort of Egyptian population and to evaluate for the first time their relation to activity, severity, disease-related disability and erosion. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms were typed by RFLP for 128 patients with RA and 125 healthy controls. The A allele, A-containing genotypes (GA and AA) of the TIM-4 and GA haplotype were present with significant higher frequency in patients with RA than healthy controls (Pc  < 0.001). These findings suggest that the A allele, A-containing genotypes (GA and AA) and GA haplotype may be a susceptibility risk factor for RA [OR = 5.83 (3.6-9.4), OR = 9.41 (5.0-17.6) and OR = 4.21 (1.07-19.2), respectively]. No associations were found between TIM genotypes and disease activity, severity or presence of erosion. However, the RA patients with GA genotype of TIM-4 have higher grade of rheumatoid factor (RF) positivity (P = 0.018), and have worse disease-related disability (P = 0.007) and worse pain (0.025). TIM-4 rs7700944 and not TIM-1 rs41297579 G>A (-1454) is associated with RA in the present cohort of Egyptian and may be a risk factor for development of RA in Egyptian. Both SNPs have no effect on disease activity, severity or erosion. However, TIM-4 GA genotype is associated with higher grade of RF positivity and worse disease-related disability and pain.

  18. Distinct role of Tim-3 in systemic lupus erythematosus and clear cell renal cell carcinoma.

    PubMed

    Zheng, Hongying; Guo, Xingqing; Tian, Qingwu; Li, Hui; Zhu, Yuanqi

    2015-01-01

    Tim-3 is considered as one of the T-cell immunoglobulin mucin (TIM) gene family members, which contributes to the activating or silencing genes, but the mechanism of Tim-3 function in mediating SLE or tumor metastasis has not been well explored. Here, we reported Tim-3 was high expressed in the peripheral blood mononuclear cells (PBMCs) of patients with SLE, detected by RT-PCR, significantly, GATA-3 mRNA expression also increased in patients with SLE, compared with the healthy control groups. The bioinformatics used to detect the TCGA database indicated the abnormal expression of Tim-3 was involved in several different cancer types. Further, the higher expression of Tim-3 in kidney renal clear cell carcinoma TCGA database indicated it was a marker for worse 5-year survival. The high expression of Tim-3 in different ccRCC cell lines was detected in both RNA level and protein level. Further, two kinds of relative Tim-3 siRNAs in ccRCC cell lines inhibit cell migration and invasion in vitro, However, the inhibition could be partially rescued by the additional GATA3 knockdown. Further, the down regulation in the RNA and protein levels of GATA3, and the negative correlation between Tim-3 and GATA3 implied that suppression of downstream GATA3 was an important mechanism by which Tim-3 triggered metastasis in ccRCC cell lines. Together, our experiments reveal the role for Tim-3 in facilitating SLE or invasive potential of ccRCC cells by either activating GATA3 or inhibiting GATA3, suggesting that Tim-3 might be a potential therapeutic target for treating SLE or clear cell renal cell carcinoma.

  19. Tim-3 identifies exhausted follicular helper T cells in breast cancer patients.

    PubMed

    Zhu, Shiguang; Lin, Jun; Qiao, Guangdong; Wang, Xingmiao; Xu, Yanping

    2016-09-01

    Breast cancer is the most common cancer diagnosed in women worldwide. Although a series of treatment options have improved the overall 5-year survival rate to 90%, individual responses still vary from patient to patient. New evidence suggested that the infiltration of CXCL13-expressing CD4(+) follicular helper cells (Tfh) in breast tumor predicted better survival. Here, we examined the regulation of Tfh function in breast cancer patients in depth. We found that the frequencies of circulating Tfh cells were not altered in breast cancer patients compared to healthy controls. However, the expression of PD-1 and Tim-3 in Tfh cells was significantly elevated in breast cancer patients. Interestingly, we observed a preferential upregulation of PD-1 in Tim-3(+) Tfh cells compared to Tim-3(-) Tfh cells. Coexpression of PD-1 and Tim-3 is typically a hallmark of functional exhaustion in chronic virus infections and tumor. To examine whether Tim-3(+) identifies exhausted Tfh cells, we stimulated Tfh cells with anti-CD3/CD28, and found that Tim-3(+) T cells expressed reduced frequencies of chemokine CXCL13 and cytokine interleukin 21 (IL-21), and contained fewer proliferating cells, than Tim-3(-) Tfh cells. Compared to those cocultured with Tim-3(-) Tfh cells, naive B cells cocultured with Tim-3(+) Tfh cells resulted in significantly less IgM, IgG and IgA production after 12 day incubation, demonstrating a reduction in Tim-3(+) Tfh-mediated B cell help. Moreover, the frequencies of Tim-3(+) Tfh cells in resected breast tumor were further upregulated than autologous blood, suggesting a participation of Tim-3(+) Tfh cells in tumor physiology. Overall, the data presented here provided new insight in the regulation of Tfh cells in breast cancer patients.

  20. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection

    PubMed Central

    Gorman, Jacob V.; Starbeck-Miller, Gabriel; Pham, Nhat-Long L.; Traver, Geri L.; Rothman, Paul B.; Harty, John T.; Colgan, John D.

    2014-01-01

    Tim-3 is a surface molecule expressed throughout the immune system that can mediate both stimulatory and inhibitory effects. Previous studies have provided evidence that Tim-3 functions to enforce CD8 T cell exhaustion, a dysfunctional state associated with chronic stimulation. In contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute and transient stimulation remains undefined. To address this knowledge gap, we examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes (LM) infection. Analysis of wild-type (WT) mice infected with LM revealed that Tim-3 was transiently expressed by activated CD8 T cells and was associated primarily with acquisition of an effector phenotype. Comparison of responses to LM by WT and Tim-3 KO mice showed that the absence of Tim-3 significantly reduced the magnitudes of both primary and secondary CD8 T cell responses, which correlated with decreased IFN-γ production and degranulation by Tim-3 KO cells stimulated with peptide antigen ex vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to LM infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following adoptive transfer into a shared WT host. In this setting, the accumulation of CD8 T cells and the generation of cytokine-producing cells were significantly reduced by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8 T cell function. Combined, our results suggest that Tim-3 can mediate a stimulatory effect on CD8 T cell responses to an acute infection. PMID:24567532

  1. Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation.

    PubMed

    Phong, Binh L; Avery, Lyndsay; Sumpter, Tina L; Gorman, Jacob V; Watkins, Simon C; Colgan, John D; Kane, Lawrence P

    2015-12-14

    T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

  2. Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.

    PubMed

    Gautron, Anne-Sophie; Dominguez-Villar, Margarita; de Marcken, Marine; Hafler, David A

    2014-09-01

    T-cell immunoglobulin and mucin domain 3 (TIM-3) is an Ig-superfamily member expressed on IFN-γ-secreting Th1 and Tc1 cells and was identified as a negative regulator of immune tolerance. TIM-3 is expressed by a subset of activated CD4(+) T cells, and anti-CD3/anti-CD28 stimulation increases both the level of expression and the number of TIM-3(+) T cells. In mice, TIM-3 is constitutively expressed on natural regulatory T (Treg) cells and has been identified as a regulatory molecule of alloimmunity through its ability to modulate CD4(+) T-cell differentiation. Here, we examined TIM-3 expression on human Treg cells to determine its role in T-cell suppression. In contrast to mice, TIM-3 is not expressed on Treg cells ex vivo but is upregulated after activation. While TIM-3(+) Treg cells with increased gene expression of LAG3, CTLA4, and FOXP3 are highly efficient suppressors of effector T (Teff) cells, TIM-3(-) Treg cells poorly suppressed Th17 cells as compared with their suppression of Th1 cells; this decreased suppression ability was associated with decreased STAT-3 expression and phosphorylation and reduced gene expression of IL10, EBI3, GZMB, PRF1, IL1Rα, and CCR6. Thus, our results suggest that TIM-3 expression on Treg cells identifies a population highly effective in inhibiting pathogenic Th1- and Th17-cell responses.

  3. Interaction of the Intermembrane Space Domain of Tim23 Protein with Mitochondrial Membranes*

    PubMed Central

    Bajaj, Rakhi; Munari, Francesca; Becker, Stefan; Zweckstetter, Markus

    2014-01-01

    Tim23 mediates protein translocation into mitochondria. Although inserted into the inner membrane, the dynamic association of its intermembrane space (IMS) domain with the outer membrane promotes protein import. However, little is known about the molecular basis of this interaction. Here, we demonstrate that the IMS domain of Tim23 tightly associates with both inner and outer mitochondrial membrane-like membranes through a hydrophobic anchor at its N terminus. The structure of membrane-bound Tim23IMS is highly dynamic, allowing recognition of both the incoming presequence and other translocase components at the translocation contact. Cardiolipin enhances Tim23 membrane attachment, suggesting that cardiolipin can influence preprotein import. PMID:25349212

  4. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    PubMed

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  5. Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

    PubMed Central

    Phong, Binh L.; Avery, Lyndsay; Sumpter, Tina L.; Gorman, Jacob V.; Watkins, Simon C.; Colgan, John D.

    2015-01-01

    T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation. PMID:26598760

  6. The Role of Tim50 in Chemoresistance and Oncogenesis of Breast Cancer

    DTIC Science & Technology

    2011-02-01

    R175H and R273H in H1299 cells. The p53 mutants, R175H and R273H, upregulated luciferase activity approximately 2.5 and 3 fold respectively, but...Tim50 Figure 3. Mutant p53 up-regulates Tim50 promoter activity. (A) H1299 cells were transfected with a plasmid containing the Tim50 promoter region...expressed at low levels in MCF-10A cells and to determine if induction of WT p53 could alter Tim50 protein expression, we employed H1299 Figure 4

  7. Infrared spectroscopy for geologic interpretation of TIMS data

    NASA Technical Reports Server (NTRS)

    Bartholomew, Mary Jane

    1986-01-01

    The Portable Field Emission Spectrometer (PFES) was designed to collect meaningful spectra in the field under climatic, thermal, and sky conditions that approximate those at the time of the overflight. The specifications and procedures of PFES are discussed. Laboratory reflectance measurements of rocks and minerals were examined for the purpose of interpreting Thermal Infrared Multispectral Scanner (TIMS) data. The capability is currently being developed to perform direct laboratory measurement of the normal spectral radiance of Earth surface materials at low temperatures (20 to 30 C) at the Jet Propulsion Laboratory.

  8. Tim-3 induces Th2-biased immunity and alternative macrophage activation during Schistosoma japonicum infection.

    PubMed

    Hou, Nan; Piao, Xianyu; Liu, Shuai; Wu, Chuang; Chen, Qijun

    2015-08-01

    T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4(+) and CD8(+) T cells, NK1.1(+) cells, and CD11b(+) cells from the livers of S. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8(+) T cells or CD11b(+) cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbers in vitro and in vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b(+) cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection.

  9. Down-regulated expression of Tim-3 promotes invasion and metastasis of colorectal cancer cells.

    PubMed

    Sun, Q Y; Qu, C H; Liu, J Q; Zhang, P; Yao, J

    2017-01-01

    To explore how Tim-3 is expressed and how its expression influences invasion and metastasis of colorectal cancer (CRC) cells. A total of 188 CRC patients were prospectively collected for this study. Meanwhile, 135 normal controls were incorporated during the same period. Intestinal samples of the CRC radical cancerous tissues, paracancerous tissues ( 5.0 cm beyond the cancer tissue) were collected for the following experiment. Furthermore, peripheral venous blood samples (10 ml) were collected from each subject. Immunohistochemical analysis, quantitative real-time polymerase chain reaction (RT-qPCR) and western blot were performed for the detection of Tim-3 in different tissues. The immunohistochemical staining results showed that a positive Tim-3 signal was localized in the cytoplasm and nucleus, observed as yellow or brown granules. Tim-3 was largely expressed in colon carcinoma tissues and normal colon mucosa tissues but was rarely expressed in the cell membrane. RT-qPCR results indicated that Tim-3 mRNA levels were significantly lower in CRC tissues than in paracancerous tissues and normal colon mucosa tissues. A trend of decreased Tim-3 mRNA levels was also found in the paracancerous tissues compared with the normal colon mucosa tissues (all P < 0.05). Western blot results revealed reduced Tim-3 protein expression in CRC tissues compared with normal colon mucosa tissues and paracancerous tissues, and Tim-3 protein expression was much lower in the paracancerous tissues than in the normal colon mucosa tissues (all P < 0.05). Furthermore, obviously lower Tim-3 mRNA levels were found in the poorly differentiated CRC patients and in those with lymph node metastasis and distant metastasis (all P < 0.05). Collectively, Tim-3 expression was mainly located in the cytoplasm and nucleus, showing down-regulated expression in colon carcinoma tissues compared with normal and paracancerous tissues. Reduced Tim-3 expression may promote CRC invasion and metastasis providing a

  10. Tim-3 Induces Th2-Biased Immunity and Alternative Macrophage Activation during Schistosoma japonicum Infection

    PubMed Central

    Hou, Nan; Piao, Xianyu; Liu, Shuai; Wu, Chuang

    2015-01-01

    T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4+ and CD8+ T cells, NK1.1+ cells, and CD11b+ cells from the livers of S. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8+ T cells or CD11b+ cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbers in vitro and in vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b+ cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection. PMID:25987707

  11. Characterization of the mitochondrial inner membrane protein translocator Tim17 from Trypanosoma brucei

    PubMed Central

    Singha, Ujjal K.; Peprah, Emmanuel; Williams, Shuntae; Walker, Robert; Saha, Lipi; Chaudhuri, Minu

    2010-01-01

    Mitochondrial protein translocation machinery in the kinetoplastid parasites, like Trypanosoma brucei, has been characterized poorly. In T. brucei genome data base, one homolog for a protein translocator of mitochondrial inner membrane (Tim) has been found, which is closely related to Tim17 from other species. The T. brucei Tim17 (TbTim17) has a molecular mass 16.2 kDa and it possesses four characteristic transmembrane domains. The protein is localized in the mitochondrial inner membrane. The level of TbTim17 protein is 6–7 fold higher in the procyclic form that has a fully active mitochondrion, than in the mammalian bloodstream form of T. brucei, where many of the mitochondrial activities are suppressed. Knockdown of TbTim17 expression by RNAi caused a cessation of cell growth in the procyclic form and reduced growth rate in the bloodstream form. Depletion of TbTim17 decreased mitochondrial membrane potential more in the procyclic than bloodstream form. However, TbTim17 knockdown reduced the expression level of several nuclear encoded mitochondrial proteins in both the forms. Furthermore, import of presequence containing nuclear encoded mitochondrial proteins was significantly reduced in TbTim17 depleted mitochondria of the procyclic as well as the bloodstream form, confirming that TbTim17 is critical for mitochondrial protein import in both developmental forms. Together, these show that TbTim17 is the translocator of nuclear encoded mitochondrial proteins and its expression is regulated according to mitochondrial activities in T. brucei. PMID:18325611

  12. Space Solar Power Technical Interchange Meeting 2: SSP TIM 2

    NASA Technical Reports Server (NTRS)

    Sanders, Jim; Hawk, Clark W.

    1998-01-01

    The 2nd Space Solar Power Technical Interchange Meeting (SSP TIM 2) was conducted September 21st through 24th with the first part consisting of a Plenary session. The summary results of this Plenary session are contained in part one of this report. The attendees were then organized into Working Breakout Sessions and Integrated Product Team (IPT) Sessions for the purpose of conducting in-depth discussions in specific topic areas and developing a consensus as to appropriate study plans and actions to be taken. The Second part covers the Plenary Summary Session, which contains the summary results of the Working Breakout Sessions and IPT Sessions. The appendix contains the list of attendees. The ob'jective was to provide an update for the study teams and develop plans for subsequent study activities. This SSP TIM 2 was initiated and the results reported electronically over the Internet. The International Space Station (ISS) could provide the following opportunities for conducting research and technology (R&T) which are applicable to SSP: (1) Automation and Robotics, (2) Advanced Power Generation, (3) Advanced Power Management & Distribution (PMAD), (4) Communications Systems and Networks, (5) Energy Storage, (6) In Space Propulsion (ISP), (7) Structural Dynamics and Control, and Assembly and (8) Wireless Power Transmission.

  13. Inhibition of in vitro and in vivo T cell responses by recombinant human Tim-1 extracellular domain proteins.

    PubMed

    Mesri, Mehdi; Smithson, Glennda; Ghatpande, Ashwini; Chapoval, Andrei; Shenoy, Suresh; Boldog, Ferenc; Hackett, Craig; Pena, Carol E; Burgess, Catherine; Bendele, Alison; Shimkets, Richard A; Starling, Gary C

    2006-03-01

    Members of the T cell, Ig domain and mucin domain (Tim) family of proteins have recently been implicated in the control of T cell-mediated immune responses. Tim-1 (HUGO designation HAVCR1) polymorphisms have been linked to the regulation of atopy in mice and humans, suggestive of a role in immune regulation. Tim-1 is expressed upon activation of T cells. In concert with the increased expression of Tim-1, a binding partner for the extracellular domain of Tim-1 (eTim-1) was induced on activated T cells, and mRNA expression data was consistent with the binding partner being Tim-4. We found that co-immobilized recombinant eTim-1 was able to inhibit T cell activation mediated by CD3 + CD28 mAb. eTim-1 mediated its inhibitory effects on proliferation by arresting cell cycle at G(0)/G(1) phase through regulation of cell cycle proteins. In vivo, administration of eTim-1 proteins led to a decrease in both ear (contact hypersensitivity to oxazolone) and joint (methylated BSA antigen-induced arthritis) swelling. The inhibitory activity of eTim-1 in the T(h)1-dependent models was evidence that eTim-1 is able to modulate T cell responses. Manipulation of the Tim-1 interaction with its binding partner on T cells may therefore provide a novel target for therapeutic intervention in T cell-mediated diseases.

  14. TIM Version 3.0 beta Technical Description and User Guide - Appendix A - User's Guidance for TIM v.3.0(beta)

    EPA Pesticide Factsheets

    Provides detailed guidance to the user on how to select input parameters for running the Terrestrial Investigation Model (TIM) and recommendations for default values that can be used when no chemical-specific or species-specific information are available.

  15. Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2.

    PubMed

    Wang, Zhiding; Sun, Dejun; Chen, Guojiang; Li, Ge; Dou, Shuaijie; Wang, Renxi; Xiao, He; Hou, Chunmei; Li, Yan; Feng, Jiannan; Shen, Beifen; Han, Gencheng

    2017-02-16

    T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection.

  16. Tim-3: Expression on immune cells and roles at the maternal-fetal interface.

    PubMed

    Hu, Xiao-Hui; Tang, Mao-Xing; Mor, Gil; Liao, Ai-Hua

    2016-11-01

    Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4(+) T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance. Tim-3 pathway also participates in regulating the activities of CD4(+) regulatory T cells, monocyte-macrophages, dendritic cells and natural killer cells. Dysregulation of Tim-3 expression can elicit excessive or inhibited inflammatory responses and ultimately result in autoimmune diseases, viral or tumor evasion and pregnancy complications. In this review, we will mainly focus on the expression of Tim-3 on local immune cells and its function in pregnancy. In addition, meaningful questions that need further investigation and the potential roles of Tim-3 in fetal tolerance will be discussed. Deeper understanding of the immune checkpoint receptor Tim-3 will shed new light on exploring the pathogenesis of some pregnancy complications, including pre-eclampsia, intrauterine growth restriction, recurrent spontaneous abortion and preterm birth. Tim-3 pathway might be a new target of immune therapy for pregnancy complications in the future.

  17. Microglia activity modulated by T cell Ig and mucin domain protein 3 (Tim-3).

    PubMed

    Wang, Hong-wei; Zhu, Xin-li; Qin, Li-ming; Qian, Hai-jun; Wang, Yiner

    2015-01-01

    Microglia are the main innate immune cells in the central nervous system that are actively involved in maintaining brain homeostasis and diseases. T cell Ig and mucin domain protein 3 (Tim-3) plays critical roles in both the adaptive and the innate immune system and is an emerging therapeutic target for treatment of various disorders. In the brain Tim-3 is specifically expressed on microglia but its functional role is unclear. Here, we showed that Tim-3 was up-regulated on microglia by ATP or LPS stimulation. Tim-3 activation with antibodies increased microglia expression of TGF-β, TNF-α and IL-1β. Blocking of Tim-3 with antibodies decreased the microglial phagocytosis of apoptotic neurons. Tim-3 blocking alleviated the detrimental effect of microglia on neurons and promoted NG2 cell differentiation in co-cultures. Finally, MAPKs namely ERK1/2 and JNK proteins were phosphorylated upon Tim-3 activation in microglia. Data indicated that Tim-3 modulates microglia activity and regulates the interaction of microglia-neural cells.

  18. Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

    PubMed Central

    Wang, Zhiding; Sun, Dejun; Chen, Guojiang; Li, Ge; Dou, Shuaijie; Wang, Renxi; Xiao, He; Hou, Chunmei; Li, Yan; Feng, Jiannan; Shen, Beifen; Han, Gencheng

    2017-01-01

    T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection. PMID:28205579

  19. GUM Analysis for TIMS Isotopic Ratios in BEP0 Graphite Qualification Samples, Round 2

    SciTech Connect

    Gerlach, David C.; Heasler, Patrick G.; Reid, Bruce D.

    2009-01-01

    In May 2007, one set of three samples from NBL were addressed to Steve Petersen for TIMS analysis, and included BEP0 samples numbered 27008, 30986, and 50846. All cores were trimmed by tooling, and lightly cleaned by CO2 pellet blasting. Small discs were cut from the second set of samples for SIMS analysis, with the remainder of each used for TIMS preparation.

  20. Identification of TIM3 2'-fluoro oligonucleotide aptamer by HT-SELEX for cancer immunotherapy.

    PubMed

    Hervas-Stubbs, Sandra; Soldevilla, Mario M; Villanueva, Helena; Mancheño, Uxua; Bendandi, Maurizio; Pastor, Fernando

    2016-01-26

    TIM3 belongs to a family of receptors that are involved in T-cell exhaustion and Treg functions. The development of new therapeutic agents to block this type of receptors is opening a new avenue in cancer immunotherapy. There are currently several clinical trials ongoing to combine different immune-checkpoint blockades to improve the outcome of cancer patients. Among these combinations we should underline PD1:PDL1 axis and TIM3 blockade, which have shown very promising results in preclinical settings. Most of these types of therapeutic agents are protein cell-derived products, which, although broadly used in clinical settings, are still subject to important limitations. In this work we identify by HT-SELEX TIM3 non-antigenic oligonucleotide aptamers (TIM3Apt) that bind with high affinity and specificity to the extracellular motives of TIM3 on the cell surface. The TIM3Apt1 in its monomeric form displays a potent antagonist capacity on TIM3-expressing lymphocytes, determining the increase of IFN-γ secretion. In colon carcinoma tumor-bearing mice, the combinatorial treatment of TIM3Apt1 and PDL1-antibody blockade is synergistic with a remarkable antitumor effect. Immunotherapeutic aptamers could represent an attractive alternative to monoclonal antibodies, as they exhibit important advantages; namely, lower antigenicity, being chemically synthesized agents with a lower price of manufacture, providing higher malleability, and antidote availability.

  1. Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome displayed aberrant differentiation, overproliferation and decreased apoptosis.

    PubMed

    Tao, Jing-lian; Li, Li-juan; Fu, Rong; Wang, Hua-quan; Jiang, Hui-juan; Yue, Lan-zhu; Zhang, Wei; Liu, Hui; Ruan, Er-bao; Qu, Wen; Wang, Guo-jin; Wang, Xiao-ming; Wu, Yu-hong; Liu, Hong; Song, Jia; Guan, Jing; Xing, Li-min; Shao, Zong-hong

    2014-06-01

    TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been clarified. Here, both the percentage of TIM3 on HSCs and the MFI of TIM3+ HSCs were higher in untreated MDS than control and were closed to AML, and excessive TIM3+ HSCs was closely related to clinical parameters: WPSS score, karyotype analysis, morphologic blasts, the number of cytopenia involving hematopoietic lineages, anemia and granulocytopenia. TIM3+ HSCs expressed lower CD11b, TpoR, EpoR, G-CSFR and Annexin V, and higher CD71 and GATA2. TIM3+ HSCs displayed aberrant differentiation, overproliferation and decreased apoptosis. TIM3 might be a promising marker for identifying malignant clone cells in MDS and a candidate for targeted therapy.

  2. Discrimination of alkalinity in granitoid Rocks: A potential TIMS application

    NASA Technical Reports Server (NTRS)

    Ruff, Steven W.

    1995-01-01

    In mineral exploration, the ability to distinguish and map petrochemical variations of magmatic rocks can be a useful reconnaissance tool. Alkalinity is one such petrochemical parameter and is used in the characterization of granitoid rocks. In quartz normative plutonic rocks, alkalinity is related to the composition and abundance of feldspars. Together with quartz abundance, knowledge of feldspar modes allows the classification of these igneous rocks according to the Streckeisen diagram. Alternative classification schemes rely on whole rock geochemistry instead of mineral identifications. The relative ease of obtaining whole rock analyses means that geochemical classifications tend to be favored in exploration geology. But the technique of thermal infrared spectroscopy of rocks yields information on mineralogy and is one that can be applied remotely. The goal of the current work then is to establish whether data from TIMS can be used to distinguish the mineralogical variations that relate to alkalinity. An ideal opportunity to test this thesis arises from the work presented in a paper by Dewitt (1989). This paper contains the results of mapping and analysis of Proterozoic plutonic rocks in north-central Arizona. The map resulting from this work delineates plutons according to alkalinity in an effort to establish a trend or polarity in the regional magmatism. Also contained within this paper are brief descriptions of the mineralogy of half of the region's plutons. This combination of mineralogical and geochemical information was the rationale behind choosing this area as a site for TIMS over flights. A portion of the region centered on the northern Bradshaw Mountains was selected because it contains plutons of all three alkalinity classifications (alkali-calcic, calc-alkalic, and calic) present on DeWitt's map within a relatively small area. The site was flown in August of 1994 and the data received a few days before the writing of this manuscript. Most of this

  3. Multicollector ICPMS and TIMS as tools for isotopic fingerprinting

    NASA Astrophysics Data System (ADS)

    Bouman, C.; Schwieters, J. B.; Lloyd, N. S.; Trinquier, A.

    2012-04-01

    Elements such as C, N, O and S are essential for chemical and biological processes in nature and very small shifts in the isotopic composition of these elements are important tracers to explore complex processes in nature. During the last few years, stable isotopes of elements as Cl, Ca, Fe, Cu, Zn, Sr, Hg and Pb are getting more and more attention as tracer to study biomedical and environmental processes, as well as forensics and archaeometry. Multi-collector ICPMS and TIMS enable high-precision isotopic analysis of these so-called non-traditional stable isotope systems. MC-ICPMS is a powerful technique for the isotopic analysis of most elements, with the exception of light elements such as H, C, N and O and the noble gases. Various inlet systems can be used to introduce samples into the mass spectrometer, for instance gas chromatography (GC), liquid chromatography (LC) ) for compound-specific isotope analysis, laser ablation for direct analysis of solids, or conventional liquid nebulization for liquid samples. The aerosol is transported by an Ar and/or He gas flow into the ICP source where it is effectively ionized and introduced into the mass analyzer through a differential pumping system. Molecular interferences as carbides, nitrides, oxides, argides or doubly-charged species can show up in the mass spectrum and interfere with the elemental isotope peaks. High mass resolution is needed to effectively discriminate against these interferences. The NEPTUNE Plus is specially designed to meet this requirement and expand the power of isotope ratio measurements even to elements where previously isobaric interferences were the limit. For some specific isotope systems, such as Ca, Sr and Pb, the thermal ionization technique may have advantages, due to the potentially lower backgrounds and higher sensitivity. Prior to the TIMS analysis, the sample is chemically purified, loaded on a filament and introduced into the mass spectrometer. With the introduction of the TRITON

  4. Impaired functional responses in follicular lymphoma CD8(+)TIM-3(+) T lymphocytes following TCR engagement.

    PubMed

    Gravelle, Pauline; Do, Catherine; Franchet, Camille; Mueller, Sabina; Oberic, Lucie; Ysebaert, Loïc; Larocca, Luigi Maria; Hohaus, Stefan; Calmels, Marie-Noëlle; Frenois, François-Xavier; Kridel, Robert; Gascoyne, Randy D; Laurent, Guy; Brousset, Pierre; Valitutti, Salvatore; Laurent, Camille

    2016-01-01

    Upregulation of T cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8(+)TIM-3(+)T cells in lymph nodes of FL patients. When compared to their CD8(+)TIM-3(-) counterparts, CD8(+)TIM-3(+) T cells exhibited defective cytokine production following TCR engagement. Furthermore, CD8(+)TIM-3(+) T cells display ex vivo markers of lytic granule release and remain unresponsive to further TCR-induced activation of the lytic machinery. Although confocal microscopy showed that TIM-3 expression on CD8(+) T cells correlated with minor alterations of immunological synapse, a selective reduction of ERK signaling in CD8(+)TIM-3(+)T cells was observed by phospho-flow analysis. Finally, short relapse-free survival despite rituximab(R)-chemotherapy was observed in patients with high content of TIM-3(+) cells and a poor infiltrate of granzyme B(+) T cells in FL lymph nodes. Together, our data indicate that, besides selective TCR early signaling defects, TIM-3 expression correlates with unresponsiveness of ex vivo CD8(+) T cells in FL. They show that scores based on the combination of exhaustion and cytolytic markers in FL microenvironment might be instrumental to identify patients at early risk of relapses following R-chemotherapy.

  5. Functional Complementation Analyses Reveal that the Single PRAT Family Protein of Trypanosoma brucei Is a Divergent Homolog of Tim17 in Saccharomyces cerevisiae

    PubMed Central

    Weems, Ebony; Singha, Ujjal K.; Hamilton, VaNae; Smith, Joseph T.; Waegemann, Karin; Mokranjac, Dejana

    2015-01-01

    Trypanosoma brucei, a parasitic protozoan that causes African trypanosomiasis, possesses a single member of the presequence and amino acid transporter (PRAT) protein family, which is referred to as TbTim17. In contrast, three homologous proteins, ScTim23, ScTim17, and ScTim22, are found in Saccharomyces cerevisiae and higher eukaryotes. Here, we show that TbTim17 cannot rescue Tim17, Tim23, or Tim22 mutants of S. cerevisiae. We expressed S. cerevisiae Tim23, Tim17, and Tim22 in T. brucei. These heterologous proteins were properly imported into mitochondria in the parasite. Further analysis revealed that although ScTim23 and ScTim17 were integrated into the mitochondrial inner membrane and assembled into a protein complex similar in size to TbTim17, only ScTim17 was stably associated with TbTim17. In contrast, ScTim22 existed as a protease-sensitive soluble protein in the T. brucei mitochondrion. In addition, the growth defect caused by TbTim17 knockdown in T. brucei was partially restored by the expression of ScTim17 but not by the expression of either ScTim23 or ScTim22, whereas the expression of TbTim17 fully complemented the growth defect caused by TbTim17 knockdown, as anticipated. Similar to the findings for cell growth, the defect in the import of mitochondrial proteins due to depletion of TbTim17 was in part restored by the expression of ScTim17 but was not complemented by the expression of either ScTim23 or ScTim22. Together, these results suggest that TbTim17 is divergent compared to ScTim23 but that its function is closer to that of ScTim17. In addition, ScTim22 could not be sorted properly in the T. brucei mitochondrion and thus failed to complement the function of TbTim17. PMID:25576485

  6. Expansion of dysfunctional Tim-3-expressing effector memory CD8+ T cells during simian immunodeficiency virus infection in rhesus macaques.

    PubMed

    Fujita, Tsuyoshi; Burwitz, Benjamin J; Chew, Glen M; Reed, Jason S; Pathak, Reesab; Seger, Elizabeth; Clayton, Kiera L; Rini, James M; Ostrowski, Mario A; Ishii, Naoto; Kuroda, Marcelo J; Hansen, Scott G; Sacha, Jonah B; Ndhlovu, Lishomwa C

    2014-12-01

    The T cell Ig- and mucin domain-containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8(+) T cells arising from chronic stimulation in viral infections like HIV. Tim-3 blockade leads to improved antiviral CD8(+) T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression. However, the Tim-3 pathway in the physiologically relevant rhesus macaque SIV model of AIDS remains uncharacterized. We report that Tim-3(+)CD8(+) T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals. Tim-3(+)PD-1(+)CD8(+) T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia. Tim-3 expression was found primarily on effector memory CD8(+) T cells in all tissues examined. Tim-3(+)CD8(+) T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3(-)CD8(+) T cells. During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8(+) T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR-driven mechanisms for Tim-3 expression. Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8(+) T cell responses.

  7. Molecular cloning, characterization and expression analysis of Tim-3 and Galectin-9 in the woodchuck model.

    PubMed

    Liu, Yanan; Wang, Junzhong; Wang, Lu; Wang, Baoju; Yang, Shangqing; Wang, Qin; Luo, Jinzhuo; Feng, Xuemei; Yang, Xuecheng; Lu, Yinping; Roggendorf, Michael; Lu, Mengji; Yang, Dongliang; Liu, Jia

    2017-03-01

    In recent years, a critical role for T cell immunoglobulin mucin domain 3 (Tim-3) and its ligand Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity and cancer. Manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. The woodchuck (Marmot monax) infected by woodchuck hepatitis virus (WHV) represents an informative animal model to study HBV infection and HCC. In the current study, the cDNA sequences of woodchuck Tim-3 and Gal-9 were cloned, sequenced and characterized. The extracellular domain of Tim-3 cDNA sequence consisted of 576bp coding sequence (CDS) that encoded 192 amino acids. The 1076bp full-length Gal-9 cDNA sequence consisted of 1059bp coding sequence (CDS) that encoded 352 amino acids with a molecular weight of 39.7kDa. The phylogenetic tree analysis revealed that the woodchuck Tim-3 and Gal-9 had the closest genetic relationship with Ictidomys tridecemlineatus. The result of quantification PCR analysis showed that ubiquitous expression of Gal-9 but not Tim-3 in different tissues of naive woodchucks. Elevated liver Gal-9 expression was observed in woodchucks with chronic WHV infection. Moreover, a polyclonal antibody against the extracellular domain of woodchuck Tim-3 were generated and identified by flow cytometry. Our results serve as a foundation for further insight into the role of Tim-3/Galectin-9 signaling pathway in viral hepatitis and HCC in the woodchuck model.

  8. The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

    PubMed

    Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

    2016-01-01

    The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

  9. Airborne Thermal Infrared Multispectral Scanner (TIMS) images over disseminated gold deposits, Osgood Mountains, Humboldt County, Nevada

    NASA Technical Reports Server (NTRS)

    Krohn, M. Dennis

    1986-01-01

    The U.S. Geological Survey (USGS) acquired airborne Thermal Infrared Multispectral Scanner (TIMS) images over several disseminated gold deposits in northern Nevada in 1983. The aerial surveys were flown to determine whether TIMS data could depict jasperoids (siliceous replacement bodies) associated with the gold deposits. The TIMS data were collected over the Pinson and Getchell Mines in the Osgood Mountains, the Carlin, Maggie Creek, Bootstrap, and other mines in the Tuscarora Mountains, and the Jerritt Canyon Mine in the Independence Mountains. The TIMS data seem to be a useful supplement to conventional geochemical exploration for disseminated gold deposits in the western United States. Siliceous outcrops are readily separable in the TIMS image from other types of host rocks. Different forms of silicification are not readily separable, yet, due to limitations of spatial resolution and spectral dynamic range. Features associated with the disseminated gold deposits, such as the large intrusive bodies and fault structures, are also resolvable on TIMS data. Inclusion of high-resolution thermal inertia data would be a useful supplement to the TIMS data.

  10. Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms.

    PubMed

    Verwei, Miriam; Minekus, Mans; Zeijdner, Evelijn; Schilderink, Ronald; Havenaar, Robert

    2016-02-10

    Pharmaceutical research needs predictive in vitro tools for API bioavailability in humans. We evaluated two dynamic in vitro gastrointestinal models: TIM-1 and tiny-TIM. Four low-soluble APIs in various formulations were investigated in the TIM systems under fasted and fed conditions. API small-intestinal bioaccessibility profiles were evaluated between the two systems and in comparison with human data. Both TIM systems showed a higher bioaccessibility of ciprofloxacin and nifedipine during 3-4h after dosing immediate release (IR) compared to modified release (MR) formulations. Higher bioaccessibility levels from IR formulations were observed under fasted state in the first 30-90 min in tiny-TIM as compared to TIM-1, resulting in a tmax similar to clinical data. Absence (ciprofloxacin) or presence (posaconazole) of a food effect on bioaccessibility was observed in both TIM systems in line with human data. A higher bioaccessibility of fenofibrate from nano- vs micro-particle formulation was found in both TIM systems. This dataset shows the predictive quality of the TIM systems for clinical data on API small-intestinal bioaccessibility from IR and MR formulations and food effects. Tiny-TIM provides higher throughput and better prediction for IR formulations. TIM-1 provides detailed information on site-specific release of APIs, relevant for MR formulations and food effects.

  11. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4.

    PubMed

    Tietjen, Gregory T; Gong, Zhiliang; Chen, Chiu-Hao; Vargas, Ernesto; Crooks, James E; Cao, Kathleen D; Heffern, Charles T R; Henderson, J Michael; Meron, Mati; Lin, Binhua; Roux, Benot; Schlossman, Mark L; Steck, Theodore L; Lee, Ka Yee C; Adams, Erin J

    2014-04-15

    Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca(2+)-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4's recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.

  12. The TIM-3 pathway ameliorates Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed

    Kaneyama, Tomoki; Tomiki, Hiroki; Tsugane, Sayaka; Inaba, Yuji; Ichikawa, Motoki; Akiba, Hisaya; Yagita, Hideo; Kim, Byung S; Koh, Chang-Sung

    2014-07-01

    Infection by Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis. T-cell immunoglobulin and mucin domain-3 (TIM-3) has been demonstrated to play a crucial role in the maintenance of peripheral tolerance. In this study, we examined the regulatory role of the TIM-3 pathway in the development of TMEV-induced demyelinating disease (TMEV-IDD). The expression of TIM-3 was increased at both protein and mRNA levels in the spinal cords of mice with TMEV-IDD compared with naive controls. In addition, by utilizing a blocking mAb, we demonstrate that TIM-3 negatively regulates TMEV-specific ex vivo production of IFN-γ and IL-10 by CD4(+) T cells and IFN-γ by CD8(+) T cells from the CNS of mice with TMEV-IDD at 36 days post-infection (dpi). In vivo blockade of TIM-3 by using the anti-TIM-3 mAb resulted in significant exacerbation of the development of TMEV-IDD both clinically and histologically. The number of infiltrating mononuclear cells in the CNS was also increased in mice administered with anti-TIM-3 mAb both at the induction phase (10 dpi) and at the effector phase (36 dpi). Flow cytometric analysis of intracellular cytokines revealed that the number of CD4(+) T cells producing TNF, IL-4, IL-10 and IL-17 was significantly increased at the effector phase in the CNS of anti-TIM-3 mAb-treated mice. These results suggest that the TIM-3 pathway plays a critical role in the regulation of TMEV-IDD.

  13. Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus.

    PubMed

    Jiao, Qingqing; Qian, Qihong; Zhao, Zuotao; Fang, Fumin; Hu, Xiaohan; An, Jingnan; Wu, Jian; Liu, Cuiping

    2016-10-01

    Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4(+) T cells, CD8(+) T cells, CD56(+) T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.

  14. Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer.

    PubMed

    Xu, Benling; Yuan, Long; Gao, Quanli; Yuan, Peng; Zhao, Peng; Yuan, Huijuan; Fan, Huijie; Li, Tiepeng; Qin, Peng; Han, Lu; Fang, Weijia; Suo, Zhenhe

    2015-08-21

    T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-γ than Tim-3-PD-1-CD8+ T cells, followed by Tim-3+PD-1-CD8+ T cells, and Tim-3-PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-γ production of Tim-3+CD8+ T cells . It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential therapeutic

  15. Abnormal expression of Tim-3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients.

    PubMed

    Liu, Hongliang; Zhi, Liqiang; Duan, Ning; Su, Pengxiao

    2016-08-01

    T-cell immunoglobulin and mucin-domain-3-containing molecule 3 (TIM-3) plays a pivotal role in immune regulation and has been found in various tumors. However, the prevalence and distribution of Tim-3 in osteosarcoma (OS) is still unclear. The aim of this study was to investigate the prevalence and distribution of Tim-3 in OS. Tim-3 on peripheral T cells from 82 OS patients and 60 healthy controls were examined by flow cytometry. Plasma levels of IL-2, IFN-γ, and TNF-α were measured by ELSIA. Tim-3 on both CD4(+) T and CD8(+) T cells were significantly upregulated in OS patients compared with healthy controls, Tim-3(+) CD4(+) T, and Tim-3(+) CD8(+) T cells were both negatively associated with serum levels of IL-2 and IFN-γ and TNF-α. In addition, Tim-3 showed similar levels in patients with different tumor sites. Nevertheless, patients with advanced tumor stage, metastasis, and pathological tumor fracture displayed significantly higher Tim-3 on both CD4(+) T cells and CD8(+) T cells than those with early tumor stage, without metastasis and pathological tumor fracture. Moreover, high Tim-3 on peripheral CD4(+) T cells or CD8(+) T were significantly related to poor overall survival (P = 0.014, P = 0.035, respectively). In conclusion, Tim-3 may be a potential diagnostic and prognostic biomarker for OS progression.

  16. Tabulating Ingestion of Mocha Solution (TIMS): a longitudinal prospective cohort study

    PubMed Central

    Staios, Gregory; Khan, Waqas U.; Chiuccariello, Lina; Sellings, Laurie H.; De Sousa, Kim; Wang, Shan; Lo, Steven; Elkader, Alexander K.

    2011-01-01

    The annual “Roll Up the Rim to Win” contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption. PMID:22159361

  17. Research of the Holiday kind: Tabulating Ingestion of Mocha Solution (TIMS): a longitudinal prospective cohort study.

    PubMed

    Staios, Gregory; Khan, Waqas U; Chiuccariello, Lina; Sellings, Laurie H; De Sousa, Kim; Wang, Shan; Lo, Steven; Elkader, Alexander K

    2011-12-13

    The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption.

  18. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients

    PubMed Central

    Sada-Ovalle, Isabel; Ocaña-Guzman, Ranferi; Pérez-Patrigeón, Santiago; Chávez-Galán, Leslie; Sierra-Madero, Juan; Torre-Bouscoulet, Luis; Addo, Marylyn M.

    2015-01-01

    Introduction T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD-1) are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviral therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. Materials and methods HIV+ patients naïve to anti-retroviral therapy (ART) were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. Results We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro

  19. Sensor 17 Thermal Isolation Mounting Structure (TIMS) Design Improvements

    SciTech Connect

    Enstrom, K.

    2015-09-04

    The SENSOR 17 thermographic camera weighs approximately 0.5lbs, has a fundamental mode of 167 Hz, and experiences 0.75W of heat leakage in through the TIMS. The configuration, shown in Figure 1, is comprised of four 300 Series SST washers paired in tandem with P.E.I (Ultem 100) washers. The SENSOR 17 sensor is mounted to a 300 series stainless plate with A-shaped arms. The Plate can be assumed to be at ambient temperatures (≈293K) and the I.R. Mount needs to be cooled to 45K. It is attached to the tip of a cryocooler by a ‘cold strap’ and is assumed to be at the temperature of the cold-strap (≈45K). During flights SENSOR 17 experiences excitations at frequencies centered around 10-30Hz, 60Hz, and 120Hz from the aircraft flight environment. The temporal progression described below depicts the 1st Modal shape at the systems resonant frequency. This simulation indicates Modal articulation will cause a pitch rate of the camera with respect to the body axis of the airplane. This articulation shows up as flutter in the camera.

  20. Tim-3 pathway controls regulatory and effector T cell balance during hepatitis C virus infection.

    PubMed

    Moorman, Jonathan P; Wang, Jia M; Zhang, Ying; Ji, Xiao J; Ma, Cheng J; Wu, Xiao Y; Jia, Zhan S; Wang, Ke S; Yao, Zhi Q

    2012-07-15

    Hepatitis C virus (HCV) is remarkable at disrupting human immunity to establish chronic infection. Upregulation of inhibitory signaling pathways (such as T cell Ig and mucin domain protein-3 [Tim-3]) and accumulation of regulatory T cells (Tregs) play pivotal roles in suppressing antiviral effector T cell (Teff) responses that are essential for viral clearance. Although the Tim-3 pathway has been shown to negatively regulate Teffs, its role in regulating Foxp3(+) Tregs is poorly explored. In this study, we investigated whether and how the Tim-3 pathway alters Foxp3(+) Treg development and function in patients with chronic HCV infection. We found that Tim-3 was upregulated, not only on IL-2-producing CD4(+)CD25(+)Foxp3(-) Teffs, but also on CD4(+)CD25(+)Foxp3(+) Tregs, which accumulate in the peripheral blood of chronically HCV-infected individuals when compared with healthy subjects. Tim-3 expression on Foxp3(+) Tregs positively correlated with expression of the proliferation marker Ki67 on Tregs, but it was inversely associated with proliferation of IL-2-producing Teffs. Moreover, Foxp3(+) Tregs were found to be more resistant to, and Foxp3(-) Teffs more sensitive to, TCR activation-induced cell apoptosis, which was reversible by blocking Tim-3 signaling. Consistent with its role in T cell proliferation and apoptosis, blockade of Tim-3 on CD4(+)CD25(+) T cells promoted expansion of Teffs more substantially than Tregs through improving STAT-5 signaling, thus correcting the imbalance of Foxp3(+) Tregs/Foxp3(-) Teffs that was induced by HCV infection. Taken together, the Tim-3 pathway appears to control Treg and Teff balance through altering cell proliferation and apoptosis during HCV infection.

  1. Tim-3 pathway affects NK cell impairment in patients with active tuberculosis.

    PubMed

    Wang, Feng; Hou, Hongyan; Wu, Shiji; Tang, Qing; Huang, Min; Yin, Botao; Huang, Jing; Liu, Weiyong; Mao, Lie; Lu, Yanfang; Sun, Ziyong

    2015-12-01

    Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.

  2. Quantitative assessment of TIM-3 polymorphisms and cancer risk in Chinese Han population.

    PubMed

    Gao, Xueren; Yang, Jiaojiao; He, Youji; Zhang, Jianqiong

    2016-06-14

    Previous studies have investigated the associations of TIM-3 polymorphisms (-1516G/T, -574G/T, and +4259T/G) with cancer risk in Chinese Han population, but the results remain conflicting. Therefore, we conducted a meta-analysis to derive a more precise estimation of the associations. The pooled data showed that TIM-3 polymorphisms (-1516G/T, -574G/T, and +4259T/G) were significantly associated with an increased risk of overall cancer in Chinese Han population. Subgroup analyses based on cancer system showed that TIM-3 -1516G/T polymorphism was only associated with an increased risk of digestive system cancer in Chinese Han population. TIM-3 -574G/T polymorphism was associated with an increased risk of digestive system cancer and other cancer in Chinese Han population. TIM-3 +4259T/G polymorphism was only associated with an increased risk of other cancer in Chinese Han population. In summary, our results indicated that TIM-3 polymorphisms (-1516G/T, -574G/T, and +4259T/G) were associated with the increased risk of cancer in Chinese Han population.

  3. Expression of Tim-3 in gastric cancer tissue and its relationship with prognosis.

    PubMed

    Cheng, Gui; Li, Min; Wu, Jun; Ji, Mei; Fang, Cheng; Shi, Hongbing; Zhu, Danxia; Chen, Lujun; Zhao, Jiemin; Shi, Liangrong; Xu, Bin; Zheng, Xiao; Wu, Changping; Jiang, Jingting

    2015-01-01

    As a negative regulatory molecule, T-cell immunoglobulin-and mucin domain-3 (Tim-3) plays a crucial role in the tumor immunological tolerance. In the present study, we aimed to determine the Tim-3 expression in gastric cancer tissue and its relationship with clinicopathological parameters and prognosis. The Tim-3 expression was assessed in 52 gastric cancer specimens and 15 gastritis tissues by flow cytometry, and gastritis tissues served as the control. As a result, we found that the Tim-3 expressions on CD4(+)T cells and CD8(+)T cells in gastric cancer tissue was significantly higher than those in gastritis tissue (P=0.022, P=0.047, respectively). The median expression level of Tim-3 on CD4(+)T cells were significantly correlated with clinicopathological parameters, such as tumor size, lymph node metastasis, the depth of tumor invasion and TNM staging (P=0.042, P=0.026, P=0.001, P=0.003, respectively), while it was not correlated with sex, age and histological subtype (all P>0.05). In CD8(+)T cells, the Tim-3 expression was relevant to tumor invasion and TNM staging (P=0.035, P=0.017, respectively), while it was irrelevant to other clinicopathological parameters (all P>0.05). Additionally, Kaplan-Meier survival curves showed that the median overall survival time of patients with lower Tim-3 expression was greater than that of patients with higher Tim-3 expression in CD4(+)T cells and CD8(+)T cells (χ(2)=18.036, P<0.001 and χ(2)=18.036, P<0.001, respectively). Moreover, the multivariate analysis revealed that the Tim-3 expression and TNM stage were independent prognostic factors for gastric cancer patients (P=0.029, P=0.043 and P=0.003, respectively). These results suggest that Tim-3 played an important role in the development and progression of gastric cancer, and it could be used as an independent prognostic factor for gastric cancer patients.

  4. Negative CD4+TIM-3 Signaling Confers Resistance Against Cold Preservation Damage in Mouse Liver Transplantation

    PubMed Central

    Zhang, Yu; Shen, Xiu-da; Gao, Feng; Nguyen, Terry T.; Shang, Xuanming; Lee, Nayun; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.

    2016-01-01

    Ischemia-reperfusion injury (IRI), an innate immunity-driven local inflammation, remains the major problem in clinical organ transplantation. T cell immunoglobulin and mucin domain (TIM-3) – Galectin-9 (Gal-9) signaling regulates CD4+ Th1 immune responses. Here, we explored TIM-3 – Gal-9 function in a clinically relevant murine model of hepatic cold storage and orthotopic liver transplantation (OLT). C57BL/6 livers, preserved for 20h at 4°C in UW solution, were transplanted to syngeneic mouse recipients. Up-regulation of TIM-3 on OLT-infiltrating activated CD4+ T cells was observed in the early IRI phase (1h). By 6h of reperfusion, OLTs in recipients treated with a blocking anti-TIM-3 Ab were characterized by: 1/ enhanced hepatocellular damage (sALT levels, liver Suzuki's histological score); 2/ polarized cell infiltrate towards Th1/Th17-type phenotype; 3/ depressed T cell exhaustion markers (PD-1, LAG3); and 4/ elevated neutrophil and macrophage infiltration/activation. In parallel studies, adoptive transfer of CD4+ T cells from naïve WT, but not from TIM-3 Tg donors, readily recreated OLT damage in otherwise IR-resistant RAG−/− test recipients. Furthermore, pre-treatment of mice with rGal-9 promoted hepatoprotection against preservation-association liver damage, accompanied by enhanced TIM-3 expression in OLTs. Thus, CD4+ T cell-dependent “negative” TIM-3 costimulation is essential for hepatic homeostasis and resistance against IR stress in OLTs. PMID:25676534

  5. Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by suppressing the NF-κB signaling pathway.

    PubMed

    Xu, Liyun; Zhao, Peiqing; Xu, Yong; Gao, Lishuang; Wang, Hongxing; Jia, Xiaoxia; Ma, Hongxin; Liang, Xiaoxong; Ma, Chunxong; Gao, Lifen

    2016-11-01

    Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.

  6. A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import

    PubMed Central

    Peleh, Valentina; Martinez-Caballero, Sonia; Sommer, Frederik; van der Laan, Martin; Schroda, Michael

    2016-01-01

    Tim17 is a central, membrane-embedded subunit of the mitochondrial protein import machinery. In this study, we show that Tim17 contains a pair of highly conserved cysteine residues that form a structural disulfide bond exposed to the intermembrane space (IMS). This disulfide bond is critical for efficient protein translocation through the TIM23 complex and for dynamic gating of its preprotein-conducting channel. The disulfide bond in Tim17 is formed during insertion of the protein into the inner membrane. Whereas the import of Tim17 depends on the binding to the IMS protein Mia40, the oxidoreductase activity of Mia40 is surprisingly dispensable for Tim17 oxidation. Our observations suggest that Tim17 can be directly oxidized by the sulfhydryl oxidase Erv1. Thus, import and oxidation of Tim17 are mediated by the mitochondrial disulfide relay, though the mechanism by which the disulfide bond in Tim17 is formed differs considerably from that of soluble IMS proteins. PMID:27502485

  7. A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import.

    PubMed

    Ramesh, Ajay; Peleh, Valentina; Martinez-Caballero, Sonia; Wollweber, Florian; Sommer, Frederik; van der Laan, Martin; Schroda, Michael; Alexander, R Todd; Campo, María Luisa; Herrmann, Johannes M

    2016-08-15

    Tim17 is a central, membrane-embedded subunit of the mitochondrial protein import machinery. In this study, we show that Tim17 contains a pair of highly conserved cysteine residues that form a structural disulfide bond exposed to the intermembrane space (IMS). This disulfide bond is critical for efficient protein translocation through the TIM23 complex and for dynamic gating of its preprotein-conducting channel. The disulfide bond in Tim17 is formed during insertion of the protein into the inner membrane. Whereas the import of Tim17 depends on the binding to the IMS protein Mia40, the oxidoreductase activity of Mia40 is surprisingly dispensable for Tim17 oxidation. Our observations suggest that Tim17 can be directly oxidized by the sulfhydryl oxidase Erv1. Thus, import and oxidation of Tim17 are mediated by the mitochondrial disulfide relay, though the mechanism by which the disulfide bond in Tim17 is formed differs considerably from that of soluble IMS proteins.

  8. Combined blockade of Tim-3 and MEK inhibitor enhances the efficacy against melanoma.

    PubMed

    Liu, Yang; Cai, Pengcheng; Wang, Ning; Zhang, Qianwen; Chen, Fenghua; Shi, Liang; Zhang, Yang; Wang, Lin; Hu, Lihua

    2017-03-04

    Insights into the role of the mitogen-activated protein kinase (MAPK) pathway and immune checkpoints have led combined targeted therapy and immunotherapy to be a promising regimen. Trametinib, as a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated effectiveness in patients with advanced melanoma. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3), an immune checkpoint molecule, participates in multiple negative regulation of antitumor immunity. We for the first time to our knowledge reported the combination of trametinib and anti-Tim-3 monoclonal antibody (mAb) in treating B16-F10 melanoma mice. We discovered that trametinib remarkably promoted apoptosis and inhibited cell proliferation while inhibition of MEK improved the expression of Tim-3 and caused the decrease of CD8(+) T cells; to the contrary, anti-Tim-3 mAb enhanced antitumor immunity by stimulating CD8(+) T cells, thus the combined therapy produced potent antitumor effect cooperatively. Taken together, our study provides compelling evidence for combining trametinib and anti-Tim-3 mAb as a potential valuable regimen in treating melanoma.

  9. TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action.

    PubMed

    Du, Wenwen; Yang, Min; Turner, Abbey; Xu, Chunling; Ferris, Robert L; Huang, Jianan; Kane, Lawrence P; Lu, Binfeng

    2017-03-16

    Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.

  10. Tim-3 and its role in regulating anti-tumor immunity.

    PubMed

    Das, Madhumita; Zhu, Chen; Kuchroo, Vijay K

    2017-03-01

    Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade. This has provided impetus to identify other co-inhibitory receptors that could be exploited to enhance response rates of current immunotherapeutic agents and achieve responses to the cancers that are refectory to immunotherapy. Tim-3 is a co-inhibitory receptor that is expressed on IFN-g-producing T cells, FoxP3+ Treg cells and innate immune cells (macrophages and dendritic cells) where it has been shown to suppress their responses upon interaction with their ligand(s). Tim-3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that in vivo blockade of Tim-3 with other check-point inhibitors enhances anti-tumor immunity and suppresses tumor growth in several preclinical tumor models. This review discusses the recent findings on Tim-3, the role it plays in regulating immune responses in different cell types and the rationale for targeting Tim-3 for effective cancer immunotherapy.

  11. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

    PubMed

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-11-24

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

  12. The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia

    PubMed Central

    Koh, Han Seok; Chang, Chi Young; Jeon, Sae-Bom; Yoon, Hee Jung; Ahn, Ye-Hyeon; Kim, Hyung-Seok; Kim, In-Hoo; Jeon, Sung Ho; Johnson, Randall S.; Park, Eun Jung

    2015-01-01

    Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases. PMID:25790768

  13. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses

    PubMed Central

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-01-01

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared. PMID:26575624

  14. The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia.

    PubMed

    Koh, Han Seok; Chang, Chi Young; Jeon, Sae-Bom; Yoon, Hee Jung; Ahn, Ye-Hyeon; Kim, Hyung-Seok; Kim, In-Hoo; Jeon, Sung Ho; Johnson, Randall S; Park, Eun Jung

    2015-03-20

    Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases.

  15. Role of Tim-3 in hepatitis B virus infection: An overview.

    PubMed

    Liu, Yuan; Gao, Li-Fen; Liang, Xiao-Hong; Ma, Chun-Hong

    2016-02-21

    Hepatitis B virus (HBV) infection has received increasing public attention. HBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the above-mentioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of HBV-related liver disease and suggest new therapeutic methods for intervention.

  16. TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

    PubMed Central

    Du, Wenwen; Yang, Min; Turner, Abbey; Xu, Chunling; Ferris, Robert L.; Huang, Jianan; Kane, Lawrence P.; Lu, Binfeng

    2017-01-01

    Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action. PMID:28300768

  17. Mexican Infrared-Optical New Technology Telescope: The TIM project

    NASA Astrophysics Data System (ADS)

    Salas, L.

    1998-11-01

    The scientific goals for TIM are an image quality of 0.25", consistent with the seeing at our site, optimization for the infrared as many scientific programs are going in that region of the spectrum, a M1 diameter in excess of 6.5 meters and a field of view limited to 10 arc minutes. Practical reasons, such as the limited funding available and the requirement of mexican financial agencies that the telescope should be built and installed in Mexico, lead us to decide for a segmented telescope, with a single secondary mirror, a single cassegrain focus and a light high stifness tubular structure. ALthough we are still working on the conceptual design of the telescope, there are some concepts that we are pursuing. The optical desing (M1+M2) is Ritchey-Cretien type with an hyperbolic primary 7.8 m od F/1.5 and a 0.9 m diameter f/15 secondary mirror. This will give a plate scale of 1.7 "/mm. This is 0.03 "/pix in direct mode, enough for AO goals. As for direct imaging, a factor of 5 reduction with 20 cm diam optical components would be able to produce 5' fields on a 2048, 20 microns type detector with 0.17"/pix. This implies that, with the use of auxiliary optics which is a common need for each particular instrument anyway, a wide variety of needs can be accomodated with a single secondary mirror. Choping for infrared observations would however introduce a additional cost in the secondary mirror. Alternatively the use of cold tertiary choping mirror is currently under study. The M1+M2 design currently aquires d80 of 0.17" in a 5' field without correction and 1" in a 10' field, that would require a field correcting lens. The M1 mirror will be segmented into 19 1.8 m diameter segments. There are 4 kinds of segments, the central, which we have kept to provide a reference for phasing, 6 more segments for the first ring and 12 in the outer ring, of two different kinds. The spacing between the segments is 5 mm, enough to reduce the inter-segment thermal background to half a

  18. BOREAS Level-1B TIMS Imagery: At-sensor Radiance in BSQ Format

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Strub, Richard; Newcomer, Jeffrey A.; Chernobieff, Sonia

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) Staff Science Aircraft Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. For BOREAS, the Thermal Infrared Multispectral Scanner (TIMS) imagery, along with other aircraft images, was collected to provide spatially extensive information over the primary study areas. The Level-1b TIMS images cover the time periods of 16 to 20 Apr 1994 and 06 to 17 Sep 1994. The system calibrated images are stored in binary image format files. The TIMS images are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  19. Disruption of TIM-4 in dendritic cell ameliorates hepatic warm IR injury through the induction of regulatory T cells.

    PubMed

    Li, Ji; Zhao, Xin; Liu, Xiaoliang; Liu, Huanqiu

    2015-08-01

    Hepatic ischaemia reperfusion (IR) injury results from the infiltration of multiple immune cells especially dendritic cells (DC). T-cell immunoglobulin-domain and mucin-domain 4 (TIM-4) is a type I cell-surface glycoprotein which is extensively expressed on antigen presenting cells (APC) like DC and macrophages. TIM-4 has been demonstrated to be implicated in mucosal allergy, skin allograft rejection and tumour-immune tolerance. However, the role of TIM-4 expressed on DC in hepatic IR injury remains largely unknown. In the present study, we aimed to investigate whether and how DC expressed TIM-4 was involved in hepatic IR injury. With segmental hepatic warm ischaemia mice models, we demonstrated that promoted DC infiltration and increased TIM-4 expression were induced by hepatic IR. Blockade of TIM-4 by anti-TIM-4 mAb (0.35mg/mouse) markedly ameliorated hepatic injury and reduced inflammatory cytokine secretion. Furthermore, in a DC:CD4+ T cell co-culture system, blockade of TIM-4 on DC significantly inhibited T helper-2 cell differentiation and facilitated induced CD4+ CD25+ Foxp3+ T regulatory cell (iTreg) expansion. Interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (Stat 6) signalling was shown to be impeded by TIM-4 blockade and involved in iTreg generation. Additionally, adoptive transfer of iTreg produced by TIM-4 blockade into hepatic IR mice models remarkably attenuated liver injury. We conclude that TIM-4 on DC play a critical role in hepatic IR injury and may be an efficient target for the prevention of liver or other organ IR injury.

  20. TIM, a ray-tracing program for METATOY research and its dissemination

    NASA Astrophysics Data System (ADS)

    Lambert, Dean; Hamilton, Alasdair C.; Constable, George; Snehanshu, Harsh; Talati, Sharvil; Courtial, Johannes

    2012-03-01

    TIM (The Interactive METATOY) is a ray-tracing program specifically tailored towards our research in METATOYs, which are optical components that appear to be able to create wave-optically forbidden light-ray fields. For this reason, TIM possesses features not found in other ray-tracing programs. TIM can either be used interactively or by modifying the openly available source code; in both cases, it can easily be run as an applet embedded in a web page. Here we describe the basic structure of TIM's source code and how to extend it, and we give examples of how we have used TIM in our own research. Program summaryProgram title: TIM Catalogue identifier: AEKY_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKY_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License No. of lines in distributed program, including test data, etc.: 124 478 No. of bytes in distributed program, including test data, etc.: 4 120 052 Distribution format: tar.gz Programming language: Java Computer: Any computer capable of running the Java Virtual Machine (JVM) 1.6 Operating system: Any; developed under Mac OS X Version 10.6 RAM: Typically 145 MB (interactive version running under Mac OS X Version 10.6) Classification: 14, 18 External routines: JAMA [1] (source code included) Nature of problem: Visualisation of scenes that include scene objects that create wave-optically forbidden light-ray fields. Solution method: Ray tracing. Unusual features: Specifically designed to visualise wave-optically forbidden light-ray fields; can visualise ray trajectories; can visualise geometric optic transformations; can create anaglyphs (for viewing with coloured "3D glasses") and random-dot autostereograms of the scene; integrable into web pages. Running time: Problem-dependent; typically seconds for a simple scene.

  1. Ultra Fast X-ray Streak Camera for TIM Based Platforms

    SciTech Connect

    Marley, E; Shepherd, R; Fulkerson, E S; James, L; Emig, J; Norman, D

    2012-05-02

    Ultra fast x-ray streak cameras are a staple for time resolved x-ray measurements. There is a need for a ten inch manipulator (TIM) based streak camera that can be fielded in a newer large scale laser facility. The LLNL ultra fast streak camera's drive electronics have been upgraded and redesigned to fit inside a TIM tube. The camera also has a new user interface that allows for remote control and data acquisition. The system has been outfitted with a new sensor package that gives the user more operational awareness and control.

  2. A quantitative analysis of TIMS data obtained on the Learjet 23 at various altitudes

    NASA Technical Reports Server (NTRS)

    Jaggi, S.

    1992-01-01

    A series of Thermal Infrared Multispectral Scanner (TIMS) data acquisition flights were conducted on the NASA Learjet 23 at different altitudes over a test site. The objective was to monitor the performance of the TIMS (its estimation of the brightness temperatures of the ground scene) with increasing altitude. The results do not show any significant correlation between the brightness temperatures and the altitude. The analysis indicates that the estimation of the temperatures is a function of the accuracy of the atmospheric correction used for each altitude.

  3. The Role of Tim50 in Chemoresistance and Oncogenesis of Breast Cancer

    DTIC Science & Technology

    2010-09-01

    oncogenic effects, protein expression was compared between a p53 null cell line ( H1299 ) stably expressing vector alone or the p53 gain of function mutants...p53-R175H and -R273H. One protein that was upregulated 2-3 fold in H1299 cells expressing the p53 gain of function mutants p53-R175H and -R273H...p53-induced chemoresistance in H1299 lung cancer cells may be due to Tim50 by using RNAi directed against Tim50. Preliminary data We wanted to test

  4. Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis.

    PubMed

    Smith, Kevin D; Fu, Michael A; Brown, Eric J

    2009-10-05

    The Tim (Timeless)-Tipin complex has been proposed to maintain genome stability by facilitating ATR-mediated Chk1 activation. However, as a replisome component, Tim-Tipin has also been suggested to couple DNA unwinding to synthesis, an activity expected to suppress single-stranded DNA (ssDNA) accumulation and limit ATR-Chk1 pathway engagement. We now demonstrate that Tim-Tipin depletion is sufficient to increase ssDNA accumulation at replication forks and stimulate ATR activity during otherwise unperturbed DNA replication. Notably, suppression of the ATR-Chk1 pathway in Tim-Tipin-deficient cells completely abrogates nucleotide incorporation in S phase, indicating that the ATR-dependent response to Tim-Tipin depletion is indispensible for continued DNA synthesis. Replication failure in ATR/Tim-deficient cells is strongly associated with synergistic increases in H2AX phosphorylation and DNA double-strand breaks, suggesting that ATR pathway activation preserves fork stability in instances of Tim-Tipin dysfunction. Together, these experiments indicate that the Tim-Tipin complex stabilizes replication forks both by preventing the accumulation of ssDNA upstream of ATR-Chk1 function and by facilitating phosphorylation of Chk1 by ATR.

  5. A polymorphism of the TIM-1 IgV domain: implications for the susceptibility to filovirus infection.

    PubMed

    Kuroda, Makoto; Fujikura, Daisuke; Noyori, Osamu; Kajihara, Masahiro; Maruyama, Junki; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato

    2014-12-12

    Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Human T-cell immunoglobulin and mucin domain 1 (TIM-1) is one of the host proteins that have been shown to promote filovirus entry into cells. In this study, we cloned TIM-1 genes from three different African green monkey kidney cell lines (Vero E6, COS-1, and BSC-1) and found that TIM-1 of Vero E6 had a 23-amino acid deletion and 6 amino acid substitutions compared with those of COS-1 and BSC-1. Interestingly, Vero E6 TIM-1 had a greater ability to promote the infectivity of vesicular stomatitis viruses pseudotyped with filovirus glycoproteins than COS-1-derived TIM-1. We further found that the increased ability of Vero E6 TIM-1 to promote virus infectivity was most likely due to a single amino acid difference between these TIM-1s. These results suggest that a polymorphism of the TIM-1 molecules is one of the factors that influence cell susceptibility to filovirus infection, providing a new insight into the molecular basis for the filovirus host range.

  6. Identification of TIM3 2′-fluoro oligonucleotide aptamer by HT-SELEX for cancer immunotherapy

    PubMed Central

    Soldevilla, Mario M.; Villanueva, Helena; Mancheño, Uxua; Bendandi, Maurizio

    2016-01-01

    TIM3 belongs to a family of receptors that are involved in T-cell exhaustion and Treg functions. The development of new therapeutic agents to block this type of receptors is opening a new avenue in cancer immunotherapy. There are currently several clinical trials ongoing to combine different immune-checkpoint blockades to improve the outcome of cancer patients. Among these combinations we should underline PD1:PDL1 axis and TIM3 blockade, which have shown very promising results in preclinical settings. Most of these types of therapeutic agents are protein cell-derived products, which, although broadly used in clinical settings, are still subject to important limitations. In this work we identify by HT-SELEX TIM3 non-antigenic oligonucleotide aptamers (TIM3Apt) that bind with high affinity and specificity to the extracellular motives of TIM3 on the cell surface. The TIM3Apt1 in its monomeric form displays a potent antagonist capacity on TIM3-expressing lymphocytes, determining the increase of IFN-γ secretion. In colon carcinoma tumor-bearing mice, the combinatorial treatment of TIM3Apt1 and PDL1-antibody blockade is synergistic with a remarkable antitumor effect. Immunotherapeutic aptamers could represent an attractive alternative to monoclonal antibodies, as they exhibit important advantages; namely, lower antigenicity, being chemically synthesized agents with a lower price of manufacture, providing higher malleability, and antidote availability. PMID:26683225

  7. TIM-3 expression in human osteosarcoma: Correlation with the expression of epithelial-mesenchymal transition-specific biomarkers

    PubMed Central

    SHANG, YONGJUN; LI, ZHANYONG; LI, HONG; XIA, HAIBO; LIN, ZHENHUA

    2013-01-01

    Signals from the T cell Ig- and mucin-domain-containing molecules (TIMs) have been demonstrated to be actively involved in regulating the progression of carcinomas. However, the expression and distribution of these molecules in osteosarcoma, the most common primary bone malignancy with poor prognosis, have not been investigated. In this study, the expression of TIMs was examined in nine invasive human osteosarcomas using immunohistochemistry, and the phenotypes were detected by dual immunofluorescence staining. Using immunohistochemistry, it was observed that only TIM-3, rather than TIM-1 or TIM-4, was expressed in these tumor specimens, where it was localized in the cytoplasm and plasma membrane of tumor cells. Dual immunofluorescence staining revealed that the expression of TIM-3 was observed in all cell types investigated, including CD68+ macrophages, CD31+ endothelial cells, CK-18+ epithelial cells and PCNA+ tumor cells. Notably, in sarcoma cells, TIM-3 was co-expressed with certain biomarkers of epithelial-mesenchymal transition (EMT), including vimentin, Slug, Snail and Smad. These combined results suggest that TIM-3 triggers tumor cells to acquire features of aggressive EMT and may be involved in the pathogenesis of this malignancy. PMID:24137353

  8. DAS performance analysis

    SciTech Connect

    Bates, G.; Bodine, S.; Carroll, T.; Keller, M.

    1984-02-01

    This report begins with an overview of the Data Acquisition System (DAS), which supports several of PPPL's experimental devices. Performance measurements which were taken on DAS and the tools used to make them are then described.

  9. Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells.

    PubMed

    Gonçalves Silva, Isabel; Gibbs, Bernhard F; Bardelli, Marco; Varani, Luca; Sumbayev, Vadim V

    2015-10-20

    The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated receptor which is involved in a variety of biological responses in human immune cells. It is highly expressed in most acute myeloid leukaemia (AML) cells and therefore may serve as a possible target for AML therapy. However, its biochemical activities in primary human AML cells remain unclear. We therefore analysed the total expression and surface presence of the Tim-3 receptor in primary human AML blasts and healthy primary human leukocytes isolated from human blood. We found that Tim-3 expression was significantly higher in primary AML cells compared to primary healthy leukocytes. Tim-3 receptor molecules were distributed largely on the surface of primary AML cells, whereas in healthy leukocytes Tim-3 protein was mainly expressed intracellularly. In primary human AML blasts, both Tim-3 agonistic antibody and galectin-9 (a Tim-3 natural ligand) significantly upregulated mTOR pathway activity. This was in line with increased accumulation of hypoxia-inducible factor 1 alpha (HIF-1α) and secretion of VEGF and TNF-α. Similar results were obtained in primary human healthy leukocytes. Importantly, in both types of primary cells, Tim-3-mediated effects were compared with those induced by lipopolysaccharide (LPS) and stem cell factor (SCF). Tim-3 induced comparatively moderate responses in both AML cells and healthy leukocytes. However, Tim-3, like LPS, mediated the release of both TNF-α and VEGF, while SCF induced mostly VEGF secretion and did not upregulate TNF-α release.

  10. Investigating Enhanced Thorium Ionization in TIMS Using Re/Pt Porous Ion Emitters

    SciTech Connect

    Floyd E. Stanley III; K. J. Spencer; D. S. Schwartz; M. G. Watrous; J. E. Delmore

    2014-03-01

    Thermal ionization mass spectrometry (TIMS) is a widely used, benchmark method in the isotopic analysis of actinides relevant to various nuclear and geological fields. Despite significant previous use and inherent advantages, however, poor sample ionization continues to hamper the use of TIMS in the measurement of trace species; actinide ionization efficiencies frequently fall below 0.1 % using traditional instrument sources. Factors leading to poor ionization are compounded in the measurement of several highly refractory metals (e.g. U and Th) that may provide key signatures data in non-proliferation, safeguards and forensics efforts. Herein, a relatively new TIMS ion source strategy, employing porous ion emitters (PIEs) atop traditional filament assemblies, is investigated for the first time as a straightforward means of enhancing the ionization of Th, which is arguably a worst case scenario for TIMS-based actinide measurements. These sources yielded up to 410% greater Th sample utilization, relative to previously published values and in-house measurements collected using traditional methods. Accompanying scanning electron microscopy (SEM) investigations provide preliminary insight into possible mechanisms of PIE functioning and explore the impacts that extended heating have on the constructed source’s structure and composition.

  11. Critical Trial Use of TIMS as an Alternative Instructional Delivery Tool

    ERIC Educational Resources Information Center

    Uy, Chin

    2005-01-01

    This quantitative-qualitative study seeks to determine the effectiveness of TIMS (Thomasian Interactive Multimedia Software) in teaching the introductory topics in Trigonometry. The acceptability of the software to the student respondents was established using the content, design, interface, and effectiveness of the media used as the evaluation…

  12. Beyond "Cain v. Horne": Comment on Tim Keller's "The National Implications of 'Cain v. Horne'"

    ERIC Educational Resources Information Center

    Harmon, Corinne

    2010-01-01

    This commentary is in response to Tim Keller's article "The National Implications of 'Cain v. Horne.'" In his analysis, Keller asserts that the Arizona Supreme Court wrongfully struck down a voucher program for students with special needs by characterizing the voucher as aid to schools rather than aid to students. In this response to…

  13. A Ghoulish Inconsistency: A Comment on Tim Keller's "The National Implications of "Cain v. Horne""

    ERIC Educational Resources Information Center

    Schoenig, John

    2010-01-01

    Tim Keller's article insightfully explores the flawed legal reasoning behind and potentially pernicious consequences of the Arizona Supreme Court's 2009 "Cain vs. Horne" ruling. He carefully examines the two fundamental flaws in the court's interpretative methodology: a failure to engage in a straightforward textual analysis of Arizona's…

  14. Constructing a Writer's Voice: Ethos, Tim Cahill, and the Jonestown Massacre

    ERIC Educational Resources Information Center

    Miller, Rich

    2007-01-01

    For over twenty years, Tim Cahill's writing has appeared in popular publications such as "Outside" and "Rolling Stone," and in many academic contexts, ranging from remedial and freshman composition textbooks to the use of his novels and short story collections in a variety of upper division literary courses. Cahill, then, is a…

  15. Onsite: A Residency with Tim Rollins/KOS. A Photo Essay.

    ERIC Educational Resources Information Center

    Placky, Robert

    2000-01-01

    Presents a photo essay that visually narrates the workshop that took place in State College, Pennsylvania, from October 19-24, 1998 bringing together middle and high school students with Tim Rollins, who is a conceptual artist and educator, and Kids of Survival (KOS). (CMK)

  16. Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria.

    PubMed

    Popov-Celeketić, Dusan; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

    2008-05-21

    The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments.

  17. Consumerism, Activism, Intrinsic Motivation, and Balance: An Interview with Tim Kasser

    ERIC Educational Resources Information Center

    Keeley, Jared

    2010-01-01

    A year after receiving his PhD in psychology from the University of Rochester, Tim Kasser accepted a position at Knox College, in Galesburg, Illinois, where he is currently professor of psychology. He regularly teaches psychology classes on personality, clinical and abnormal psychology, dreaming, and research methods, as well as an…

  18. Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion

    PubMed Central

    Huang, Xiaoyuan; Bai, Xiangyang; Cao, Yang; Wu, Jingyi; Huang, Mei; Tang, Duozhuang; Tao, Si; Zhu, Tao; Liu, Yanling; Yang, Yang; Zhou, Xiaoxi; Zhao, Yanxia; Wu, Mingfu; Wei, Juncheng; Wang, Daowen; Xu, Gang; Wang, Shixuan

    2010-01-01

    Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3–expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4+ T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases. PMID:20176801

  19. Reading and Understanding: Tim O'Brien and the Narrative of Failure

    ERIC Educational Resources Information Center

    Buchanan, Jeffrey

    2008-01-01

    Tim O'Brien's "The Things They Carried" is an example of what the author calls a narrative of failure. A narrative of failure is a term for a narrative that both fails in the enactment of its own telling and that takes failure or failing as one of its subjects. This paper discusses how, as a form for telling a teaching story, narratives…

  20. The Filmmaker as Humanist: An Interview with Tim Robbins on the Making of "Cradle Will Rock".

    ERIC Educational Resources Information Center

    Mason, Terrence C.

    2000-01-01

    Presents an interview with Tim Robbins that focuses on the making of the film "Cradle Will Rock." Robbins offers his perspectives on issues such as the power of art to convey important social messages and sources of violence in schools. Includes resources for teachers. (CMK)

  1. T-bet-mediated Tim-3 expression dampens monocyte function during chronic hepatitis C virus infection.

    PubMed

    Yi, Wenjing; Zhang, Peixin; Liang, Yan; Zhou, Yun; Shen, Huanjun; Fan, Chao; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhansheng; Zhang, Ying

    2017-03-01

    Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/Mφ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/Mφ in the setting of HCV infection. We demonstrate that T-bet is constitutively expressed in resting CD14(+) M/Mφ in the peripheral blood. M/Mφ from chronically HCV-infected individuals exhibit a significant increase in T-bet expression that positively correlates with an increased level of Tim-3 expression. Up-regulation of T-bet is also observed in CD14(+) M/Mφ incubated with HCV(+) Huh7.5 cells, as well as in primary M/Mφ or monocytic THP-1 cells exposed to HCV core protein in vitro, which is reversible by blocking HCV core/gC1qR interactions. Moreover, the HCV core-induced up-regulation of T-bet and Tim-3 expression in M/Mφ can be abrogated by incubating the cells with SP600125 - an inhibitor for the c-Jun N-terminal kinase (JNK) signalling pathway. Importantly, silencing T-bet gene expression decreases Tim-3 expression and enhances interleukin-12 secretion as well as signal transducer and activator of transcription 1 phosphorylation. These data suggest that T-bet, induced by the HCV core/gC1qR interaction, enhances Tim-3 expression via the JNK pathway, leading to dampened M/Mφ function during HCV infection. These findings reveal a novel mechanism for Tim-3 regulation via T-bet during HCV infection, providing new targets to combat this global epidemic viral disease.

  2. Reversibility and two state behaviour in the thermal unfolding of oligomeric TIM barrel proteins.

    PubMed

    Romero-Romero, Sergio; Costas, Miguel; Rodríguez-Romero, Adela; Alejandro Fernández-Velasco, D

    2015-08-28

    Temperature is one of the main variables that modulate protein function and stability. Thermodynamic studies of oligomeric proteins, the dominant protein natural form, have been often hampered because irreversible aggregation and/or slow reactions are common. There are no reports on the reversible equilibrium thermal unfolding of proteins composed of (β/α)8 barrel subunits, albeit this "TIM barrel" topology is one of the most abundant and versatile in nature. We studied the eponymous TIM barrel, triosephosphate isomerase (TIM), belonging to five species of different bacterial taxa. All of them were found to be catalytically efficient dimers. The three-dimensional structure of four enzymes was solved at high/medium resolution. Irreversibility and kinetic control were observed in the thermal unfolding of two TIMs, while for the other three the thermal unfolding was found to follow a two-state equilibrium reversible process. Shifts in the global stability curves of these three proteins are related to the organismal temperature range of optimal growth and modulated by variations in maximum stability temperature and in the enthalpy change at that temperature. Reversibility appears to correlate with the low isoelectric point, the absence of a residual structure in the unfolded state, small cavity volume in the native state, low conformational stability and a low melting temperature. Furthermore, the strong coupling between dimer dissociation and monomer unfolding may reduce aggregation and favour reversibility. It is therefore very thought-provoking to find that a common topological ensemble, such as the TIM barrel, can unfold/refold in the Anfinsen way, i.e. without the help of the cellular machinery.

  3. Tucumán ionospheric model (TIM): Initial results for STEC predictions

    NASA Astrophysics Data System (ADS)

    Scidá, L. A.; Ezquer, R. G.; Cabrera, M. A.; Jadur, C.; Sfer, A. M.

    2016-09-01

    Most ionospheric models can calculate vertical total electron content (VTEC) predictions, but only a few are suitable for calculating slant total electron content (STEC). This ionospheric magnitude is generally measured for electron content determinations, with VTEC particularly corresponding to an elevation of 90°. This is generally obtained by applying a mapping function to STEC measurements, which leads to important calculation errors. Moreover, the equatorial region has unique characteristics, such as the fountain effect and the equatorial electrojet, which lead to significant errors in the model's calculations. In this paper, the Tucumán ionospheric model (TIM) is presented as a novel alternative for calculating the STEC in low-latitude regions (-24 to 24 dip latitude). The model is based on spatial geometry where the considered trajectory is segmented, and the corresponding electron density calculations for the resulting segment end points are determined using the semi-empirical low-latitude ionospheric model (SLIM) with reference to their corresponding magnetic coordinates and height. Finally, the electron density values are integrated along the path to obtain the STEC. This work describes the TIM and tests their STEC predictions for five ray paths around the world (totaling 16 cases under study), which are compared with experimental data from satellites and with those calculated by the NeQuick model. Moreover, the TIM performance for VTEC predictions is also checked and compared with VTEC data obtained from Global Positioning System (GPS) signals, IRI model, and NeQuick model predictions, for six GPS receiver stations during the equinox and solstice (totaling 12 cases studied). Comparisons of the TIM predictions with experimental data show that 53% of the calculation has, in general, deviations <30%. For the considered cases, TIM reproduces the experimental data better than the other models.

  4. Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages.

    PubMed

    Wong, Kit; Valdez, Patricia A; Tan, Christine; Yeh, Sherry; Hongo, Jo-Anne; Ouyang, Wenjun

    2010-05-11

    Tim-4 is a phosphatidylserine (PS) receptor that is expressed on various macrophage subsets. It mediates phagocytosis of apoptotic cells by peritoneal macrophages. The in vivo functions of Tim-4 in phagocytosis and immune responses, however, are still unclear. In this study, we show that Tim-4 quickly forms punctate caps on contact with apoptotic cells, in contrast to its normal diffused expression on the surface of phagocytes. Despite its expression in marginal zone and tingible body macrophages, Tim-4 deficiency only minimally affects outcomes of several acute immune challenges, including the trapping of apoptotic cells in the marginal zone, the clearance apoptotic cells by tingible body macrophages, and the formation of germinal centers and elicitation of antibody responses against sheep red blood cells (SRBCs). In addition, Tim-4(-/-) resident peritoneal macrophages (rPMs) phagocytose necrotic cells and other opsonized targets normally. However, their ability to bind and engulf apoptotic cells is significantly compromised both in vitro and in vivo. Most importantly, Tim-4 deficiency results in increased cellularity in the peritoneum. Resting rPMs produce higher TNF-alpha in culture. Their response to LPS, on the contrary, is dampened. Our data support an indispensible role of Tim-4 in maintaining the homeostasis of rPMs.

  5. Expression of the galectin-9-Tim-3 pathway in glioma tissues is associated with the clinical manifestations of glioma.

    PubMed

    Liu, Zengjin; Han, Huamin; He, Xin; Li, Shouwei; Wu, Chenxing; Yu, Chunjiang; Wang, Shengdian

    2016-03-01

    Glioma is known to induce local and systemic immunosuppression, which inhibits antitumor T cell responses. The galectin-9-Tim-3-pathway negatively regulates T cell pathways in the tumor immunosuppressive environment. The present study assessed the expression of Tim-3 and galectin-9 in glioma patients, and evaluated the association between the expression of Tim-3 and galectin-9 with clinical characteristics. The present study identified that Tim-3 expression was significantly increased in peripheral blood T cells of glioma patients compared with those of healthy controls, and was additionally increased on tumor-infiltrating T cells. The expression of Tim-3 on tumor-infiltrating T cells was associated with the World Health Organization (WHO) grade of glioma, but negatively correlated with the Karnofsky Performance Status score of the glioma patients. Immunohistochemical analysis revealed that the expression of galectin-9 in tumor tissues was associated with Tim-3 expression on tumor-infiltrating T cells and the WHO grade of glioma. These findings suggest that the galectin-9-Tim-3 pathway may be critical in the immunoevasion of glioma and may be a potent target for immunotherapy in glioma patients.

  6. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity.

    PubMed

    Angiari, Stefano; Donnarumma, Tiziano; Rossi, Barbara; Dusi, Silvia; Pietronigro, Enrica; Zenaro, Elena; Della Bianca, Vittorina; Toffali, Lara; Piacentino, Gennj; Budui, Simona; Rennert, Paul; Xiao, Sheng; Laudanna, Carlo; Casasnovas, Jose M; Kuchroo, Vijay K; Constantin, Gabriela

    2014-04-17

    Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper 1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but it reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 immunoglobulin variable domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease.

  7. Tim-3 is highly expressed in T cells in acute myeloid leukemia and associated with clinicopathological prognostic stratification.

    PubMed

    Li, Caixia; Chen, Xiaochen; Yu, Xiao; Zhu, Yibei; Ma, Chao; Xia, Rui; Ma, Jinfeng; Gu, Caihong; Ye, Lu; Wu, Depei

    2014-01-01

    T cells immunoglobulin mucin 3 (Tim-3) is an important inhibitory stimulatory molecule, which has been reported to play a vital role in the tumor immune escape and be correlated with clinicopathological prognostic stratification in solid tumor. However, the related research is rare of Tim-3 in non-solid tumor, such as acute myeloid leukemia (AML). In this study, we investigated the expression characteristics of Tim-3 on the peripheral blood T cells of newly diagnosed AML patients and its clinical significance. Peripheral blood was obtained from 36 patients with newly diagnosed AML before intervention, with peripheral blood from 20 cases of healthy volunteers collected as normal control. Expression levels of Tim-3 on the peripheral blood T cells were assayed with flow cytometry. We found that Tim-3 expression on the peripheral blood CD4+ T cells and CD8+ T cells in newly diagnosed AML patients were significantly increased compared with that of normal control. CD4+ T cells/CD8+ T cell ratio (CD4/CD8) of peripheral blood in AML patients was significantly correlated with NCCN high risk group. The higher expression level of Tim-3 on CD4+ T cells in the peripheral blood of AML patients had significant correlation with FLT3-ITD mutation, the higher expression level of Tim-3 on CD8+ T cells in AML patients was significantly correlated with NCCN high risk group. To conclude, our results support the concept that Tim-3 is highly expressed on the peripheral blood T cells of AML patients, and Tim-3 expression significantly correlates with clinicopathological prognostic stratification in AMLTim-3, T cell, acute myeloid leukemia, tumor immune escape, clinicopathological prognostic stratification.

  8. Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3)

    PubMed Central

    Homayouni, Vida; Ganjalikhani-hakemi, Mazdak; Rezaei, Abbas; Khanahmad, Hossein; Behdani, Mahdi; Lomedasht, Fatemeh Kazemi

    2016-01-01

    Objective(s): As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. Materials and Methods: We immunized a camel with TIM-3 antigen and then, synthesized a VHH phage: mid library from its B cell’s transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA) column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines. Results: Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line. Conclusion: Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro. PMID:27917276

  9. TIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer

    PubMed Central

    Sakuishi, Kaori; Ngiow, Shin Foong; Sullivan, Jenna M.; Teng, Michele W. L.; Kuchroo, Vijay K.; Smyth, Mark J.; Anderson, Ana C.

    2013-01-01

    T-cell immunoglobulin mucin 3 (TIM3) is an inhibitory molecule that has emerged as a key regulator of dysfunctional or exhausted CD8+ T cells arising in chronic diseases such as cancer. In addition to exhausted CD8+ T cells, highly suppressive regulatory T cells (Tregs) represent a significant barrier against the induction of antitumor immunity. We have found that the majority of intratumoral FOXP3+ Tregs express TIM3. TIM3+ Tregs co-express PD-1, are highly suppressive and comprise a specialized subset of tissue Tregs that are rarely observed in the peripheral tissues or blood of tumor-bearing mice. The co-blockade of the TIM3 and PD-1 signaling pathways in vivo results in the downregulation of molecules associated with TIM3+ Treg suppressor functions. This suggests that the potent clinical efficacy of co-blocking TIM3 and PD-1 signal transduction cascades likely stems from the reversal of T-cell exhaustion combined with the inhibition of regulatory T-cell function in tumor tissues. Interestingly, we find that TIM3+ Tregs accumulate in the tumor tissue prior to the appearance of exhausted CD8+ T cells, and that the depletion of Tregs at this stage interferes with the development of the exhausted phenotype by CD8+ T cells. Collectively, our data indicate that TIM3 marks highly suppressive tissue-resident Tregs that play an important role in shaping the antitumor immune response in situ, increasing the value of TIM3-targeting therapeutic strategies against cancer. PMID:23734331

  10. TIM-4 is differentially expressed in the distinct subsets of dendritic cells in skin and skin-draining lymph nodes and controls skin Langerhans cell homeostasis.

    PubMed

    Zhang, Xilin; Liu, Queping; Wang, Jie; Li, Guihua; Weiland, Matthew; Yu, Fu-Shin; Mi, Qing-Sheng; Gu, Jun; Zhou, Li

    2016-06-21

    T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on dendritic cells (DC) and macrophages, plays an essential role in regulating immune responses. Langerhans cells (LC), which are the sole DC subpopulation residing at the epidermis, are potent mediators of immune surveillance and tolerance. However, the significance of TIM-4 on epidermal LCs, along with other cutaneous DCs, remains totally unexplored. For the first time, we discovered that epidermal LCs expressed TIM-4 and displayed an increased level of TIM-4 expression upon migration. We also found that dermal CD207+ DCs and lymph node (LN) resident CD207-CD4+ DCs highly expressed TIM-4, while dermal CD207- DCs and LN CD207-CD4- DCs had limited TIM-4 expressions. Using TIM-4-deficient mice, we further demonstrated that loss of TIM-4 significantly upregulated the frequencies of epidermal LCs and LN resident CD207-CD4+ DCs. In spite of this, the epidermal LCs of TIM-4-deficient mice displayed normal phagocytic and migratory abilities, comparable maturation status upon the stimulation as well as normal repopulation under the inflamed state. Moreover, lack of TIM-4 did not affect dinitrofluorobenzene-induced contact hypersensitivity response. In conclusion, our results indicated that TIM-4 was differentially expressed in the distinct subsets of DCs in skin and skin-draining LNs, and specifically regulated epidermal LC and LN CD207-CD4+ DC homeostasis.

  11. Tim-3 Is Upregulated in NK Cells during Early Pregnancy and Inhibits NK Cytotoxicity toward Trophoblast in Galectin-9 Dependent Pathway

    PubMed Central

    Sun, Jintang; Yang, Meixiang; Ban, Yanli; Gao, Wenjuan; Song, Bingfeng; Wang, Yang; Zhang, Yun; Shao, Qianqian; Kong, Beihua; Qu, Xun

    2016-01-01

    NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear. Here, we showed Tim-3 was mainly expressed by decidual NK cells (dNK) and Tim-3 level in dNK was higher than peripheral NK cells (pNK). Tim-3+ dNK expressed more levels of mature markers CD94 and CD69 than Tim-3- dNK cells and blocking Tim-3 significantly inhibited dNK IFN-γ and TNF-α secretion. Furthermore, we found TGF-β1 may contribute to such up-regulation of Tim-3 in NK cells. Interestingly, blocking Tim-3 enhanced NK cytotoxicity toward trophoblast cell line HTR-8 but not K562. We found HTR-8 expressed Tim-3 ligand Galectin-9, in contrast K562 did not. Small interfering RNA-mediated silencing of Galectin-9 expression enhanced NK cytotoxicity toward HTR-8. We further showed Tim-3/Galecin-9 inhibited NK cytotoxicity toward trophoblast partially via impairing the degranulation process. In addition, clinical data showed that abnormal Tim-3 level on pNK might be associated with recurrent spontaneous abortion (RSA). Thus, our data demonstrate Tim-3/Galectin-9 pathway maintains local tolerance by suppressing NK cytotoxicity toward trophoblasts which may represent a new immunologic tolerance mechanism at MFI. PMID:26789128

  12. Tim-3 Is Upregulated in NK Cells during Early Pregnancy and Inhibits NK Cytotoxicity toward Trophoblast in Galectin-9 Dependent Pathway.

    PubMed

    Sun, Jintang; Yang, Meixiang; Ban, Yanli; Gao, Wenjuan; Song, Bingfeng; Wang, Yang; Zhang, Yun; Shao, Qianqian; Kong, Beihua; Qu, Xun

    2016-01-01

    NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear. Here, we showed Tim-3 was mainly expressed by decidual NK cells (dNK) and Tim-3 level in dNK was higher than peripheral NK cells (pNK). Tim-3(+) dNK expressed more levels of mature markers CD94 and CD69 than Tim-3- dNK cells and blocking Tim-3 significantly inhibited dNK IFN-γ and TNF-α secretion. Furthermore, we found TGF-β1 may contribute to such up-regulation of Tim-3 in NK cells. Interestingly, blocking Tim-3 enhanced NK cytotoxicity toward trophoblast cell line HTR-8 but not K562. We found HTR-8 expressed Tim-3 ligand Galectin-9, in contrast K562 did not. Small interfering RNA-mediated silencing of Galectin-9 expression enhanced NK cytotoxicity toward HTR-8. We further showed Tim-3/Galecin-9 inhibited NK cytotoxicity toward trophoblast partially via impairing the degranulation process. In addition, clinical data showed that abnormal Tim-3 level on pNK might be associated with recurrent spontaneous abortion (RSA). Thus, our data demonstrate Tim-3/Galectin-9 pathway maintains local tolerance by suppressing NK cytotoxicity toward trophoblasts which may represent a new immunologic tolerance mechanism at MFI.

  13. Correlation of fitness landscapes from three orthologous TIM barrels originates from sequence and structure constraints

    PubMed Central

    Chan, Yvonne H.; Venev, Sergey V.; Zeldovich, Konstantin B.; Matthews, C. Robert

    2017-01-01

    Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape and suggest that fitness landscapes can be translocated in sequence space. Exploration of fitness landscapes in the context of a protein fold provides a strategy for elucidating the sequence-structure-fitness relationships in other common motifs. PMID:28262665

  14. The use of TIMS for mapping different pahoehoe surfaces: Mauna Iki, Kilauea

    NASA Technical Reports Server (NTRS)

    Rowland, Scott K.

    1992-01-01

    S-type and p-type pahoehoe record different mechanisms and vigors of activity within an active flow field. There is some controversy about what these mechanisms are exactly, and this study was undertaken with the idea that an accurate map of the two surfaces within a pahoehoe flow field could be helpful in solving the problem. Thermal Infrared Multispectral Scanner (TIMS) allows discrimination between s-type and p-type pahoehoe, and this ability was used to map the two surface types on the Mauna Iki satellite shield (southwest rift zone, Kilauea Volcano). TIMS was previously used to discriminate a'a from pahoehoe as well as to determine relative age relationships of different flows. Although inter-flow variation was minor in the data published by these authors, a second goal presented is to understand such variations to better constrain intra-flow differences used for age dating.

  15. A multipurpose TIM-based optical telescope for Omega and the Trident laser facilities

    SciTech Connect

    Oertel, J.A.; Murphy, T.J.; Berggren, R.R.

    1998-12-31

    The authors have recently designed and are building a telescope which acts as an imaging light collector relaying the image to an optical table for experiment dependent analysis and recording. The expected primary use of this instrument is a streaked optical pyrometer for witness plate measurements of Hohlraum drive temperature. The telescope is based on University of Rochester`s Ten-Inch Manipulator (TIM) which allows compatibility between Omega, Trident, and the NIF lasers. The optics capture a f/7 cone of light, have a field of view of 6-mm, have a spatial resolution of 5 to 7-{micro}m per line pair at the object plane, and are optimized for operation at 280-nm. The image is at a magnification of 11.7x, which is convenient for many experiments, but can be changed using additional optics that reside outside the TIM.

  16. Zircon U-Pb analyses by TIMS and LA-ICPMS on the same material

    NASA Astrophysics Data System (ADS)

    Mundil, R.; Gehrels, G.; Deino, A. L.; Irmis, R. B.

    2008-12-01

    A number of U-Pb geochronological techniques are now available, each of which has pros and cons associated with spatial resolution, accuracy, precision and also operating cost and throughput. Zircon U-Pb age analyses using TIMS (Thermal Ionization Mass Spectrometry) can yield geological dates with uncertainties at or below the 1 permil level (precision and accuracy), but consume relatively large amounts of material (entire crystals of fragments) and are cost and time intensive. Conversely, LA-ICPMS (Laser Ablation Inductively Coupled Plasma Mass Spectrometry) geochronology is a relatively inexpensive and fast micro-sampling technique, but individual and combined uncertainties are significantly greater. The choice of a specific approach depends primarily on the nature of the geological problem; a combination of several techniques is often advisable. We present new TIMS and LA-ICPMS results on zircons from an intraformational conglomerate within the Chinle Fm (Late Triassic), and from a volcanic ash within the Late Jurassic Morrison Fm (with additional 40Ar/39Ar analyses on phenocrystic sanidine). Preliminary TIMS analyses on annealed and chemically abraded zircons from the Chinle Fm conglomerate indicate an age of ca 215.3 ± 0.9 Ma (further analyses are expected to reduce the uncertainty significantly). Previous analyses using LA-ICPMS techniques on non-polished zircons yield an age which is significantly younger (212 ± 1.5 Ma). TIMS analyses were done on the same crystals as the LA-ICPMS analyses, only one of four crystals yields an overlapping age with the ICPMS date (most of the TIMS ages are older than the corresponding LA-ICPMS ages). Part of this discrepancy may be due the fact that the LA-ICP ages preferentially suffer from surface correlated Pb loss. This effect may be mitigated by LA-ICPMS analyses on polished crystals; however, it has been shown that Pb loss also occurs within the crystal interior. Zircons from the Morrison show a similar bias in sense

  17. HHrep: de novo protein repeat detection and the origin of TIM barrels

    PubMed Central

    Söding, Johannes; Remmert, Michael; Biegert, Andreas

    2006-01-01

    HHrep is a web server for the de novo identification of repeats in protein sequences, which is based on the pairwise comparison of profile hidden Markov models (HMMs). Its main strength is its sensitivity, allowing it to detect highly divergent repeat units in protein sequences whose repeats could as yet only be detected from their structures. Examples include sequences with β-propellor fold, ferredoxin-like fold, double psi barrels or (βα)8 (TIM) barrels. We illustrate this with proteins from four superfamilies of TIM barrels by revealing a clear 4- and 8-fold symmetry, which we detect solely from their sequences. This symmetry might be the trace of an ancient origin through duplication of a βαβα or βα unit. HHrep can be accessed at . PMID:16844977

  18. HHrep: de novo protein repeat detection and the origin of TIM barrels.

    PubMed

    Söding, Johannes; Remmert, Michael; Biegert, Andreas

    2006-07-01

    HHrep is a web server for the de novo identification of repeats in protein sequences, which is based on the pairwise comparison of profile hidden Markov models (HMMs). Its main strength is its sensitivity, allowing it to detect highly divergent repeat units in protein sequences whose repeats could as yet only be detected from their structures. Examples include sequences with beta-propellor fold, ferredoxin-like fold, double psi barrels or (betaalpha)8 (TIM) barrels. We illustrate this with proteins from four superfamilies of TIM barrels by revealing a clear 4- and 8-fold symmetry, which we detect solely from their sequences. This symmetry might be the trace of an ancient origin through duplication of a betaalphabetaalpha or betaalpha unit. HHrep can be accessed at http://hhrep.tuebingen.mpg.de.

  19. Insights into the Fold Organization of TIM Barrel from Interaction Energy Based Structure Networks

    PubMed Central

    Vijayabaskar, M. S.; Vishveshwara, Saraswathi

    2012-01-01

    There are many well-known examples of proteins with low sequence similarity, adopting the same structural fold. This aspect of sequence-structure relationship has been extensively studied both experimentally and theoretically, however with limited success. Most of the studies consider remote homology or “sequence conservation” as the basis for their understanding. Recently “interaction energy” based network formalism (Protein Energy Networks (PENs)) was developed to understand the determinants of protein structures. In this paper we have used these PENs to investigate the common non-covalent interactions and their collective features which stabilize the TIM barrel fold. We have also developed a method of aligning PENs in order to understand the spatial conservation of interactions in the fold. We have identified key common interactions responsible for the conservation of the TIM fold, despite high sequence dissimilarity. For instance, the central beta barrel of the TIM fold is stabilized by long-range high energy electrostatic interactions and low-energy contiguous vdW interactions in certain families. The other interfaces like the helix-sheet or the helix-helix seem to be devoid of any high energy conserved interactions. Conserved interactions in the loop regions around the catalytic site of the TIM fold have also been identified, pointing out their significance in both structural and functional evolution. Based on these investigations, we have developed a novel network based phylogenetic analysis for remote homologues, which can perform better than sequence based phylogeny. Such an analysis is more meaningful from both structural and functional evolutionary perspective. We believe that the information obtained through the “interaction conservation” viewpoint and the subsequently developed method of structure network alignment, can shed new light in the fields of fold organization and de novo computational protein design. PMID:22615547

  20. Chronic toxicity evaluation of the Savannah River Site DETF discharges and three locations on Tims Branch

    SciTech Connect

    Not Available

    1990-10-01

    Chronic toxicity tests with Ceriodaphnia dubia were conducted June 6--August 1, 1990, on the Savannah River Site M-Area supernate discharge effluent (M-004), the A-014 effluent discharge with and without DETF process flow, and for stream samples collected in Tims Branch upstream and downstream from A-014. A secondary objective of the study was to determine what DETF flow rate would not cause instream impact to the aquatic community. 2 figs., 68 tabs.

  1. TIM-3 Genetic Variations Affect Susceptibility to Osteoarthritis by Interfering with Interferon Gamma in CD4+ T Cells.

    PubMed

    Li, Shufeng; Ren, Yanjun; Peng, Dayong; Yuan, Zhen; Shan, Shiying; Sun, Huaqiang; Yan, Xinfeng; Xiao, Hong; Li, Guang; Song, Haihan

    2015-10-01

    Osteoarthritis (OA) is the most common type of arthritis, in which T cell responses and cytokines may play critical roles in the development of the disease. TIM-3 may affect immune responses and is correlated with decreased expression of interferon gamma (INF-γ) in CD4+ T cells. In the current study, we investigated the association between polymorphisms in the TIM-3 gene and susceptibility to OA. Two polymorphisms in TIM-3, -574G/T and +4259T/G polymorphisms, were identified in OA cases and healthy donors by polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that the prevalence of TIM-3 +4259T/G genotype was significantly elevated in OA patients than in the healthy donors after adjustment (Odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.32-5.11, P < 0.001). Similarly, the TIM-3 +4259G allele presented a positive association with the risk of OA after adjustment (OR = 2.58, 95% CI 1.29-4.82, P = 0.003). The TIM-3 -574G/T polymorphism did not show any correlation with the disease. We further examined whether the two TIM-3 polymorphisms could affect INF-γ expression in CD4+ T cells. Data revealed that subjects carrying polymorphic +4259TG genotype had significantly higher mRNA and protein levels of INF-γ in CD4+ T cells compared to wild-type GG genotype (P < 0.001 and P < 0.01). These results indicated that TIM-3 polymorphism is associated with increased susceptibility to OA possibly by upregulating INF-γ expression in CD4+ T cells.

  2. Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition.

    PubMed

    Feng, Z M; Guo, S M

    2016-09-02

    The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

  3. TIMS 1.6 micron Measurement of Atmospheric CO2 and CH4

    NASA Astrophysics Data System (ADS)

    Rairden, R. L.; Kumer, J. B.; Roche, A. E.; Palmer, A.

    2013-12-01

    The Tropospheric Infrared Mapping Spectrometers (TIMS) were originally developed with support from the NASA ESTO Instrument Incubator program (IIP). These were designed to operate in the spectral regions of the CO overtone and fundamental bands at about 2.33 and 4.67 microns, respectively. In the IIP it was shown these could provide measurements of CO vertical structure, with area coverage rate and spatial resolution that would satisfy GEO-CAPE requirements as laid out in the NRC Decadal Survey report. Since completion of the IIP there has been further internally supported development discussed by Kumer et al, Aerospace Conference, 2013 IEEE. In this presentation we describe a demonstration of TIMS capability in a third wavelength region with two orders operating from approximately 1602 to 1616 nm, and from 1646 to 1660 nm. We will discuss and illustrate the reversible conversion of the 2.33 TIMS for operation at 1600 - 1660 nm; the high quality of the spectral mages and excellent agreement with models; and automated calibration algorithms. The figures show a wavelength calibrated spectral image and excellent agreement of the data and model on a spectrum extracted from the image. Fig 1. Wavelength-calibrated image of sunlight through atmosphere, with methane lines. Yellow box outlines the rows averaged for profile. Fig 2. Calibrated spectral profile, data fit to modeled atmosphere H2O, CO2, and CH4.

  4. TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma.

    PubMed

    Horlad, Hasita; Ohnishi, Koji; Ma, Chaoya; Fujiwara, Yukio; Niino, Daisuke; Ohshima, Koichi; Jinushi, Masahisa; Matsuoka, Masao; Takeya, Motohiro; Komohara, Yoshihiro

    2016-08-01

    Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL.

  5. Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients.

    PubMed

    Zhang, Yang; Cai, Pengcheng; Li, Lei; Shi, Liang; Chang, Panpan; Liang, Tao; Yang, Qianqian; Liu, Yang; Wang, Lin; Hu, Lihua

    2017-02-01

    T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8(+) T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8(+) T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells. Furthermore, TIM-3(+)CEACAM1(+) CD8(+) T cells represented the most dysfunctional population with the least IFN-γ production. In addition, the expressions of TIM-3 and CEACAM1 were correlated with advanced stage and could be independent risk factors for CRC. We for the first time to our knowledge suggested that co-expression of TIM-3 and CEACAM1 can mediate T cell exhaustion and may be potential biomarkers for CRC prediction, highlighting the possibility of being immunotherapy targets.

  6. TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

    PubMed Central

    Horlad, Hasita; Ohnishi, Koji; Ma, Chaoya; Fujiwara, Yukio; Niino, Daisuke; Ohshima, Koichi; Jinushi, Masahisa; Matsuoka, Masao; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL. PMID:27446463

  7. Space Solar Power Exploratory Research and Technology (SERT) Technical Interchange Meeting 2 (SERT TIM 2)

    NASA Technical Reports Server (NTRS)

    Howell, Joe; Sanders, Clark W.

    2000-01-01

    The University of Alabama in Huntsville's (UAH) Propulsion Research Center hosted the Space Solar Power Exploratory Research & Technology (SERT) Technical Interchange Meeting TIM) 2 in Huntsville, Alabama December 7-10. 1999 with 126 people in attendance. The SERT program includes both competitively procured activities. which are being implemented through a portfolio of focused R&D investments--with the maximum leveraging of existing resources inside and outside NASA. and guided by these system studies. Axel Roth. Director of the Flight Projects Directorate NASA MSFC, welcomed the SERT TIM 2 participants and challenged them to develop the necessary technologies and demonstrations that will lead to Space Solar Power (SSP) International implementation. Joe Howell, NASA MSFC, reiterated the SERT TIM 2 objectives: 1) Refining and modeling systems approaches for the utilization of SSP concepts and technologies, ranging, from the near-term e.g. for space science, exploration and commercial space applications to the far-term (e. g. SSP for terrestrial markets), including systems concepts, technology, infrastructure (i.g., transportation), and economics. 2) Conducting technology research, development and demonstration activities to produce "proof- of-concept" validation of critical SSP elements for both the nearer and farther-term applications. 3) Initiating partnerships Nationality and Internationally that could be expanded, as appropriate, to pursue later SSP technology and applications (e.g., space science. colonization, etc.). Day one began with the NASA Centers presenting their SERT activities summary since SERT TIM 1 and wound up with a presentation by Masahiro Mori, NASDA titled "NASDA In-house Study for SSP". Demonstration for the Near-Term. Day two began with the SERT Systems Studies and Analysis reports resulting from NRA 8-23 followed by presentations of SERT Technology Demonstrations reports resulting from NRA 8-23. Day two closed with John Mankins presentation

  8. TIM-3 Suppresses Anti-CD3/CD28-Induced TCR Activation and IL-2 Expression through the NFAT Signaling Pathway.

    PubMed

    Tomkowicz, Brian; Walsh, Eileen; Cotty, Adam; Verona, Raluca; Sabins, Nina; Kaplan, Fred; Santulli-Marotto, Sandy; Chin, Chen-Ni; Mooney, Jill; Lingham, Russell B; Naso, Michael; McCabe, Timothy

    2015-01-01

    TIM-3 (T cell immunoglobulin and mucin-domain containing protein 3) is a member of the TIM family of proteins that is preferentially expressed on Th1 polarized CD4+ and CD8+ T cells. Recent studies indicate that TIM-3 serves as a negative regulator of T cell function (i.e. T cell dependent immune responses, proliferation, tolerance, and exhaustion). Despite having no recognizable inhibitory signaling motifs, the intracellular tail of TIM-3 is apparently indispensable for function. Specifically, the conserved residues Y265/Y272 and surrounding amino acids appear to be critical for function. Mechanistically, several studies suggest that TIM-3 can associate with interleukin inducible T cell kinase (ITK), the Src kinases Fyn and Lck, and the p85 phosphatidylinositol 3-kinase (PI3K) adaptor protein to positively or negatively regulate IL-2 production via NF-κB/NFAT signaling pathways. To begin to address this discrepancy, we examined the effect of TIM-3 in two model systems. First, we generated several Jurkat T cell lines stably expressing human TIM-3 or murine CD28-ECD/human TIM-3 intracellular tail chimeras and examined the effects that TIM-3 exerts on T cell Receptor (TCR)-mediated activation, cytokine secretion, promoter activity, and protein kinase association. In this model, our results demonstrate that TIM-3 inhibits several TCR-mediated phenotypes: i) NF-kB/NFAT activation, ii) CD69 expression, and iii) suppression of IL-2 secretion. To confirm our Jurkat cell observations we developed a primary human CD8+ cell system that expresses endogenous levels of TIM-3. Upon TCR ligation, we observed the loss of NFAT reporter activity and IL-2 secretion, and identified the association of Src kinase Lck, and PLC-γ with TIM-3. Taken together, our results support the conclusion that TIM-3 is a negative regulator of TCR-function by attenuating activation signals mediated by CD3/CD28 co-stimulation.

  9. Professor Tim de Zeeuw Takes Up Duty as New ESO Director General

    NASA Astrophysics Data System (ADS)

    2007-09-01

    On 1 September, Tim de Zeeuw became the new ESO Director General, succeeding Catherine Cesarsky. In his first day in office, he kindly agreed to answer a few questions. ESO PR Photo 38/07 ESO PR Video 38/07 Watch the Video! How would you describe the current period for astronomy? Tim de Zeeuw: We are in an extremely exciting time for astronomy and I think this is understood worldwide and not just by astronomers. The technology is now available to look not only at the farthest objects in the Universe, where the light left a long time ago, allowing us to see how the Universe evolved and developed, but we can even detect signatures of planets around other stars, and that answers an age-old question which is a fundamental question in all of science, and really excites the general public. How do you see the role of ESO in this context? Tim de Zeeuw: ESO has a very important role in the context of European and worldwide astronomy because it is one of the leading organisations for ground-based astronomy. You may even say it is the pre-eminent organisation. Therefore, we have both an opportunity and a responsibility to lead the further developments in astronomy. Where do you see ESO developing in the coming years? Tim de Zeeuw: I see three main goals for ESO in the coming years. The first one is to get the best possible science out of the Very Large Telescope, the interferometer and the survey telescopes, all of them on Paranal. The second is to build ALMA, the new observatory at 5 000 metres in the high Andes. Together with our North American and East Asian partners, we need to deliver this on budget and on time, and prepare the European astronomers for leading the science. The third main goal is to design a world-leading Extremely Large Telescope (ELT), which may have a main mirror with a diameter larger than 40 metres and will enable wonderful science. And of course, we don't only want to design it, we also want to construct it. And what about La Silla? Tim de Zeeuw: La

  10. Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia

    PubMed Central

    Miko, Eva; Meggyes, Matyas; Bogar, Barbara; Schmitz, Nora; Barakonyi, Aliz; Varnagy, Akos; Farkas, Balint; Tamas, Peter; Bodis, Jozsef; Szekeres-Bartho, Julia; Illes, Zsolt; Szereday, Laszlo

    2013-01-01

    Background Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction. Methods The aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry. Results Investigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56dim NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56dim NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia. Conclusion These data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered

  11. Recipient T-Cell TIM-3 and Hepatocyte Galectin-9 Signaling Protects Mouse Liver Transplants Against Ischemia-Reperfusion Injury

    PubMed Central

    Liu, Yuanxing; Ji, Haofeng; Zhang, Yu; Shen, Xiuda; Gao, Feng; He, Xiangyi; Li, Gabriella A.; Busuttil, Ronald W.; Kuchroo, Vijay K.; Kupiec-Weglinski, Jerzy W.

    2015-01-01

    Background & Aims By binding to T-cell immunoglobulin mucin-3 (TIM-3) on activated Th1 cells, Galectin-9 (Gal-9) negatively regulates Th1-type alloimmunity. Although T cells contribute to hepatic ischemia-reperfusion injury (IRI), it is unknown whether negative T cell-dependent TIM-3 costimulation may rescue IR-stressed orthotopic liver transplants (OLT) from innate immunity-driven inflammation. Methods We used WT and TIM-3Tg mice (C57BL6) as liver donors and recipients in a clinically-relevant model of hepatic cold storage (20h at 4°C in UW solution) and syngeneic OLT. Results OLTs in WT or TIM-3Tg->TIM-3Tg groups were resistant against IR- stress, evidenced by preserved hepatocellular function (sALT levels) and liver architecture (Suzuki’s score). In contrast, OLTs in WT or TIM-3Tg->WT groups were susceptible to IRI. TIM-3 induction in recipient circulating CD4+ T cells: 1/ depressed Tbet/IFN-γ, while amplifying GATA3 and IL-4/IL-10 expression in OLTs; 2/ promoted T cell exhaustion (PD-1, LAG-3) phenotype; and 3/ depressed neutrophil and macrophage infiltration/function in OLTs. In parallel studies, we have documented, for the first time that Gal-9, a natural TIM-3 ligand, was produced primarily by and released from IR-stressed hepatocytes, both in-vivo and in-vitro. Moreover, exogenous rGal-9 potentiated liver resistance against IRI by depressing T cell activation and promoting apoptosis of CD4+ T cells. Conclusion Harnessing TIM-3–Gal-9 signaling at T cell–hepatocyte interface facilitates homeostasis in IR-stressed OLTs. Enhancing anti-oxidant hepatocyte Gal-9 potentiates liver IR-resistance. Negative regulation by recipient TIM-3+CD4+ cells provides evidence for cytoprotective functions of a discrete T cell subset, which should be spared when applying T cell-targeted immunosuppression in transplant recipients. PMID:25450716

  12. Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

    PubMed Central

    Rhein, Bethany A.; Brouillette, Rachel B.; Schaack, Grace A.; Chiorini, John A.

    2016-01-01

    ABSTRACT Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion–TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. IMPORTANCE With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many

  13. Tim de Zeeuw to Become the Next Director General of ESO

    NASA Astrophysics Data System (ADS)

    2007-01-01

    The ESO Council has just appointed Tim de Zeeuw, 50, as the next Director General of ESO, effective as of 1 September 2007, when the current Director General, Catherine Cesarsky will complete her mandate. ESO PR Photo 02/07 ESO PR Photo 03/07 Professor Tim de Zeeuw "ESO is Europe's flagship organisation for ground-based astronomy," said, Richard Wade, President of the ESO Council. "The ESO Council is very pleased that Professor de Zeeuw has accepted the task as its next Director General. He has played a key role over the last few years in developing a strategic vision for ESO, and I have every confidence that he will now lead the organisation in the realisation of that exciting vision." Tim de Zeeuw has an excellent record, both as a highly respected scientist and as a leader of an internationally recognised science institute in the Netherlands. He is Scientific Director of the Leiden Observatory, a research institute in the College of Mathematics and Natural Sciences of Leiden University. Tim de Zeeuw also has considerable experience as regards science policy issues. Catherine Cesarsky, ESO's current Director General commented: "Over the recent years, ESO has developed considerably with more activities and new member states, and with its ambitious project portfolio, ESO is clearly facing an exciting future. I shall be delighted to pass the baton to Tim de Zeeuw, who as a recent Council member is very familiar with our Organisation." "It is a great honour and an exciting challenge to lead this world-class organisation in the years to come in support of one of the most dynamic areas of science today," said de Zeeuw. "I look forward to overseeing the continued upgrading of the Very Large Telescope with the second-generation instrumentation and the completion of the ALMA project, and in particular to help developing the future European Extremely Large Telescope." Tim de Zeeuw's main research interests embrace the formation, structure and dynamics of galaxies

  14. CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients.

    PubMed

    Zhang, Yong; Zhang, Xiuying; Xia, Yan; Jia, Xiao; Li, Hao; Zhang, Yanyan; Shao, Zhen; Xin, Ning; Guo, Mingfeng; Chen, Jing; Zheng, ShuangShuang; Wang, YuZhong; Fu, Linlin; Xiao, Chenghua; Geng, Deqin; Liu, Yonghai; Cui, Guiyun; Dong, Ruiguo; Huang, Xiaoyu; Yu, Tingyan

    2016-12-01

    T cell immunoglobulin mucin domain-1(Tim-1) was recently identified to be critical and essential for optimal regulatory B cells function in maintaining immune tolerance. We aimed to measure the expression levels of Tim-1 on B cells from patients with Myasthenia Gravis (MG) and to investigate whether the expression of Tim-1 is associated with pathogenesis of MG. A total of 34 patients with MG (18 generalized MG (GMG) and 16 ocular MG (OMG) and 24 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and flow cytometry were used to measure the levels of Tim-1 expressed on peripheral B cells. Peripheral CD138+ plasma cells were assayed by flow cytometry. Serum Th17-related cytokines (IL-6, IL-1β and IL-17) and anti-AChR antibody (Ab) titers were tested by enzyme-linked immunosorbent assay (ELISA). Our data demonstrated that the mRNA and protein expression levels of B cell Tim-1 in both the GMG and OMG groups were significantly lower than those in healthy controls, with lower expression in GMG than in OMG. Tim-1 expression on B cells from OMG/GMG was negatively correlated with clinical severity, plasma cells frequency, serum Th17-related cytokines and anti-AChR Ab levels. Our results indicated that aberrant expression of Tim-1 exists on B cells and may contribute to the Th17 polarization and antibody-secreting plasma cells differentiation in MG patients.

  15. Interference with Tim-3 protein expression attenuates the invasion of clear cell renal cell carcinoma and aggravates anoikis

    PubMed Central

    Yu, Muming; Lu, Bin; Liu, Yancun; Me, Ying; Wang, Lijun; Li, Hui

    2017-01-01

    Tumor cells resistant to anoikis are considered to be candidates for metastasis. In the present study, the role of Tim-3 in anoikis and its influence on the invasion of clear cell renal cell carcinoma (ccRCC) was investigated. Here, polyhydroxylethylmethacrylate (poly-HEMA) was applied to two ccRCC cell lines, 786-O and Caki-2, to induce detachment from the extracellular matrix (ECM). Tim-3 mRNA and protein expression levels were assayed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively. Anoikis was measured by Ho33342/PI double staining, acridine orange staining, and further determined using the CytoSelect™ 24-well Anoikis Assay kit. Apoptosis was measured using flow cytometry, E-cadherin and N-cadherin protein expression were determined using western blotting and a Chemicon cell invasion assay kit was used to quantify the invasive capacity of 786-O and Caki-2 cells. It was demonstrated that detachment from the ECM decreases transcription and the protein expression level of Tim-3 in 786-O and Caki-2 cells compared with control cells. Interference with Tim-3 expression using small interfering RNA exacerbated anoikis in 786-O and Caki-2 cells induced by poly-HEMA treatment. E-cadherin upregulation, N-cadherin downregulation, and ECM detachment-induced reduction in invasion ability were all exacerbated by knockdown of Tim-3. In conclusion, interference with Tim-3 expression may attenuate the invasion of renal cell carcinoma by aggravating anoikis, indicating Tim-3 as a potential therapeutic target for treating ccRCC. PMID:28112366

  16. The Influence of Tim-3 Signaling on Central Nervous System Autoimmune Disease is Determined by the Effector Function of the Pathogenic T Cells

    PubMed Central

    Lee, Sarah Y.; Goverman, Joan M.

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) mediated by self-reactive, myelin-specific T cells. Both CD4+ and CD8+ T cells play important roles in the pathogenesis of MS. MS is studied using experimental autoimmune encephalomyelitis (EAE), an animal model mediated by myelin-specific T cells. Tim-3 is a cell-surface receptor expressed on CD4+ IFN-γ-secreting Th1 cells, and triggering Tim-3 signaling ameliorated EAE by inducing death in pathogenic Th1 cells in vivo. This suggested that enhancing Tim-3 signaling might be beneficial in patients with MS. However, Tim-3 is also expressed on activated CD8+ T cells, microglia, and dendritic cells (DCs), and the combined effect of manipulating Tim-3 signaling on these cell types during CNS autoimmunity is unknown. Furthermore, CD4+ IL-17-secreting Th17 cells also play a rolein MS but do not express high levels of Tim-3. We investigated Tim-3 signaling in EAE models that include myelin-specific Th17, Th1 and CD8+ T cells. We found that preventing Tim-3 signaling in CD4+ T cells altered the inflammatory pattern in the CNS due to differential effects on Th1 versus Th17 cells. In contrast, preventing Tim-3 signaling during CD8+ T cell-mediated EAE exacerbated disease. We also analyzed the importance of Tim-3 signaling in EAE in innate immune cells. Tim-3 signaling in DCs and microglia did not affect the manifestation of EAE in these models. These results indicate that the therapeutic efficacy of targeting Tim-3 in EAE is dependent on the nature of the effector T cells contributing to the disease. PMID:23562810

  17. A Disintegrin and Metalloprotease (ADAM) 10 and ADAM17 Are Major Sheddases of T Cell Immunoglobulin and Mucin Domain 3 (Tim-3)*

    PubMed Central

    Möller-Hackbarth, Katja; Dewitz, Christin; Schweigert, Olga; Trad, Ahmad; Garbers, Christoph; Rose-John, Stefan; Scheller, Jürgen

    2013-01-01

    T cell immunoglobulin and mucin domain 3 (Tim-3) dampens the response of CD4+ and CD8+ effector T cells via induction of cell death and/or T cell exhaustion and enhances the ability of macrophages to clear pathogens via binding to galectin 9. Here we provide evidence that human Tim-3 is a target of A disintegrin and metalloprotease (ADAM)-mediated ectodomain shedding resulting in a soluble form of Tim-3. We identified ADAM10 and ADAM17 as major sheddases of Tim-3 as shown by ADAM-specific inhibitors and the ADAM10 pro-domain in HEK293 cells and ADAM10/ADAM17-deficient murine embryonic fibroblasts. PMA-induced shedding of Tim-3 was abrogated by deletion of amino acids Glu181–Asp190 of the stalk region and Tim-3 lacking the intracellular domain was not efficiently cleaved after PMA stimulation. Surprisingly, a single lysine residue within the intracellular domain rescues shedding of Tim-3. Shedding of endogenous Tim-3 was found in primary human CD14+ monocytes after PMA and ionomycin stimulation. Importantly, the recently described down-regulation of Tim-3 from Toll-like receptor-activated CD14+ monocytes was caused by ADAM10- and ADAM17-mediated shedding. Inhibition of Tim-3 shedding from lipopolysaccharide-induced monocytes did not influence lipopolysaccharide-induced TNFα and IL-6 but increases IL-12 expression. In summary, we describe Tim-3 as novel target for ADAM-mediated ectodomain shedding and suggest a role of Tim-3 shedding in TLR-mediated immune responses of CD14+ monocytes. PMID:24121505

  18. Detection and mapping of volcanic rock assemblages and associated hydrothermal alteration with Thermal Infrared Multiband Scanner (TIMS) data Comstock Lode Mining District, Virginia City, Nevada

    NASA Technical Reports Server (NTRS)

    Taranik, James V.; Hutsinpiller, Amy; Borengasser, Marcus

    1986-01-01

    Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the Virginia City area on September 12, 1984. The data were acquired at approximately 1130 hours local time (1723 IRIG). The TIMS data were analyzed using both photointerpretation and digital processing techniques. Karhuen-Loeve transformations were utilized to display variations in radiant spectral emittance. The TIMS image data were compared with color infrared metric camera photography, LANDSAT Thematic Mapper (TM) data, and key areas were photographed in the field.

  19. Tumor-infiltrating Tim-3(+) T cells proliferate avidly except when PD-1 is co-expressed: Evidence for intracellular cross talk.

    PubMed

    Li, Jing; Shayan, Gulidanna; Avery, Lyndsay; Jie, Hyun-Bae; Gildener-Leapman, Neil; Schmitt, Nicole; Lu, Bin Feng; Kane, Lawrence P; Ferris, Robert L

    2016-01-01

    Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3. We investigated the phenotypic and functional characteristics of T cells with differential expression of PD-1 (high/low) and Tim-3 (positive/negative), using TIL directly isolated from head and neck squamous cell carcinomas (HNSCC). Unexpectedly, we found that expression of Tim-3 alone does not necessarily mark TIL as dysfunctional/exhausted. In Tim-3-TIL, PD-1 levels correlate with T cell dysfunction, with a PD-1(low/intermed) phenotype identifying recently activated and still functional cells, whereas PD-1(hi)Tim-3(-) T cells are actually exhausted. Nonetheless, PD-1(intermed) cells are still potently suppressed by PD-L1. PD-1 expression was associated with reduced phosphorylation of ribosomal protein S6 (pS6), whereas Tim-3 expression was associated with increased pS6. Using a novel mouse model for inducible Tim-3 expression, we confirmed that expression of Tim-3 does not necessarily render T cells refractory to further activation. These results suggest the existence of PD-1 and Tim-3 crosstalk in regulating antitumor T cell responses, with important implications for anti-PD-1 immunotherapy.

  20. Tim-3 promotes tumor-promoting M2 macrophage polarization by binding to STAT1 and suppressing the STAT1-miR-155 signaling axis.

    PubMed

    Jiang, Xingwei; Zhou, Tingting; Xiao, Yan; Yu, Jiahui; Dou, Shuaijie; Chen, Guojiang; Wang, Renxi; Xiao, He; Hou, Chunmei; Wang, Wei; Shi, Qingzhu; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Li, Yan; Han, Gencheng

    2016-01-01

    T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer. The Tim-3 signaling pathway in macrophages was explored using microarray, co-immunoprecipitation, gene mutation, and high-content analysis. For the first time, we demonstrated that Tim-3 polarizes macrophages by directly binding to STAT1 via residue Y256 and Y263 in its intracellular tail and inhibiting the STAT1-miR-155-SOCS1 signaling axis. We also identified a new signaling adaptor of Tim-3 in macrophages, and, by modulating the Tim-3 pathway, demonstrated the feasibility of altering macrophage polarization as a potential tool for treating this kind of disease.

  1. Summaries of the Fifth Annual JPL Airborne Earth Science Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1995-01-01

    This publication is the second volume of the summaries for the Fifth Annual JPL Airborne Earth Science Workshop, held in Pasadena, California, on January 23-26, 1995. The main workshop is divided into three smaller workshops as follows: (1) The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop on January 23-24. The summaries for this workshop appear in Volume 1; (2) The Airborne Synthetic Aperture Radar (AIRSAR) workshop on January 25-26. The summaries for this workshop appear in volume 3; and (3) The Thermal Infrared Multispectral Scanner (TIMS) workshop on January 26. The summaries for this workshop appear in this volume.

  2. Summaries of the Third Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1992-01-01

    This publication contains the preliminary agenda and summaries for the Third Annual JPL Airborne Geoscience Workshop, held at the Jet Propulsion Laboratory, Pasadena, California, on 1-5 June 1992. This main workshop is divided into three smaller workshops as follows: (1) the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on June 1 and 2; the summaries for this workshop appear in Volume 1; (2) the Thermal Infrared Multispectral Scanner (TIMS) workshop, on June 3; the summaries for this workshop appear in Volume 2; and (3) the Airborne Synthetic Aperture Radar (AIRSAR) workshop, on June 4 and 5; the summaries for this workshop appear in Volume 3.

  3. Second NASA Technical Interchange Meeting (TIM): Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box (TTB)

    NASA Technical Reports Server (NTRS)

    ONeil, D. A.; Mankins, J. C.; Christensen, C. B.; Gresham, E. C.

    2005-01-01

    The Advanced Technology Lifecycle Analysis System (ATLAS), a spreadsheet analysis tool suite, applies parametric equations for sizing and lifecycle cost estimation. Performance, operation, and programmatic data used by the equations come from a Technology Tool Box (TTB) database. In this second TTB Technical Interchange Meeting (TIM), technologists, system model developers, and architecture analysts discussed methods for modeling technology decisions in spreadsheet models, identified specific technology parameters, and defined detailed development requirements. This Conference Publication captures the consensus of the discussions and provides narrative explanations of the tool suite, the database, and applications of ATLAS within NASA s changing environment.

  4. Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex.

    PubMed

    Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

    2011-06-01

    The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion.

  5. High-precision isotopic characterization of USGS reference materials by TIMS and MC-ICP-MS

    NASA Astrophysics Data System (ADS)

    Weis, Dominique; Kieffer, Bruno; Maerschalk, Claude; Barling, Jane; de Jong, Jeroen; Williams, Gwen A.; Hanano, Diane; Pretorius, Wilma; Mattielli, Nadine; Scoates, James S.; Goolaerts, Arnaud; Friedman, Richard M.; Mahoney, J. Brian

    2006-08-01

    The Pacific Centre for Isotopic and Geochemical Research (PCIGR) at the University of British Columbia has undertaken a systematic analysis of the isotopic (Sr, Nd, and Pb) compositions and concentrations of a broad compositional range of U.S. Geological Survey (USGS) reference materials, including basalt (BCR-1, 2; BHVO-1, 2), andesite (AGV-1, 2), rhyolite (RGM-1, 2), syenite (STM-1, 2), granodiorite (GSP-2), and granite (G-2, 3). USGS rock reference materials are geochemically well characterized, but there is neither a systematic methodology nor a database for radiogenic isotopic compositions, even for the widely used BCR-1. This investigation represents the first comprehensive, systematic analysis of the isotopic composition and concentration of USGS reference materials and provides an important database for the isotopic community. In addition, the range of equipment at the PCIGR, including a Nu Instruments Plasma MC-ICP-MS, a Thermo Finnigan Triton TIMS, and a Thermo Finnigan Element2 HR-ICP-MS, permits an assessment and comparison of the precision and accuracy of isotopic analyses determined by both the TIMS and MC-ICP-MS methods (e.g., Nd isotopic compositions). For each of the reference materials, 5 to 10 complete replicate analyses provide coherent isotopic results, all with external precision below 30 ppm (2 SD) for Sr and Nd isotopic compositions (27 and 24 ppm for TIMS and MC-ICP-MS, respectively). Our results also show that the first- and second-generation USGS reference materials have homogeneous Sr and Nd isotopic compositions. Nd isotopic compositions by MC-ICP-MS and TIMS agree to within 15 ppm for all reference materials. Interlaboratory MC-ICP-MS comparisons show excellent agreement for Pb isotopic compositions; however, the reproducibility is not as good as for Sr and Nd. A careful, sequential leaching experiment of three first- and second-generation reference materials (BCR, BHVO, AGV) indicates that the heterogeneity in Pb isotopic compositions

  6. Summaries of the 4th Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1993-01-01

    This is volume 2 of a three volume set of publications that contain the summaries for the Fourth Annual JPL Airborne Geoscience Workshop, held in Washington, D.C. on October 25-29, 1993. The main workshop is divided into three smaller workshops as follows: The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on October 25-26. The summaries for this workshop appear in Volume 1. The Thermal Infrared Multispectral Scanner (TIMS) workshop, on October 27. The summaries for this workshop appear in Volume 2. The Airborne Synthetic Aperture Radar (AIRSAR) workshop, on October 28-29. The summaries for this workshop appear in Volume 3.

  7. AVIRIS and TIMS data processing and distribution at the land processes distributed active archive center

    NASA Technical Reports Server (NTRS)

    Mah, G. R.; Myers, J.

    1993-01-01

    The U.S. Government has initiated the Global Change Research program, a systematic study of the Earth as a complete system. NASA's contribution of the Global Change Research Program is the Earth Observing System (EOS), a series of orbital sensor platforms and an associated data processing and distribution system. The EOS Data and Information System (EOSDIS) is the archiving, production, and distribution system for data collected by the EOS space segment and uses a multilayer architecture for processing, archiving, and distributing EOS data. The first layer consists of the spacecraft ground stations and processing facilities that receive the raw data from the orbiting platforms and then separate the data by individual sensors. The second layer consists of Distributed Active Archive Centers (DAAC) that process, distribute, and archive the sensor data. The third layer consists of a user science processing network. The EOSDIS is being developed in a phased implementation. The initial phase, Version 0, is a prototype of the operational system. Version 0 activities are based upon existing systems and are designed to provide an EOSDIS-like capability for information management and distribution. An important science support task is the creation of simulated data sets for EOS instruments from precursor aircraft or satellite data. The Land Processes DAAC, at the EROS Data Center (EDC), is responsible for archiving and processing EOS precursor data from airborne instruments such as the Thermal Infrared Multispectral Scanner (TIMS), the Thematic Mapper Simulator (TMS), and Airborne Visible and Infrared Imaging Spectrometer (AVIRIS). AVIRIS, TIMS, and TMS are flown by the NASA-Ames Research Center ARC) on an ER-2. The ER-2 flies at 65000 feet and can carry up to three sensors simultaneously. Most jointly collected data sets are somewhat boresighted and roughly registered. The instrument data are being used to construct data sets that simulate the spectral and spatial

  8. A field- and laboratory-based quantitative analysis of alluvium: Relating analytical results to TIMS data

    NASA Technical Reports Server (NTRS)

    Wenrich, Melissa L.; Hamilton, Victoria E.; Christensen, Philip R.

    1995-01-01

    Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the McDowell Mountains northeast of Scottsdale, Arizona during August 1994. The raw data were processed to emphasize lithologic differences using a decorrelation stretch and assigning bands 5, 3, and 1 to red, green, and blue, respectively. Processed data of alluvium flanking the mountains exhibit moderate color variation. The objective of this study was to determine, using a quantitative approach, what environmental variable(s), in the absence of bedrock, is/are responsible for influencing the spectral properties of the desert alluvial surface.

  9. Role of Tim17 in coupling the import motor to the translocation channel of the mitochondrial presequence translocase

    PubMed Central

    Demishtein-Zohary, Keren; Günsel, Umut; Marom, Milit; Banerjee, Rupa; Neupert, Walter; Azem, Abdussalam; Mokranjac, Dejana

    2017-01-01

    The majority of mitochondrial proteins use N-terminal presequences for targeting to mitochondria and are translocated by the presequence translocase. During translocation, proteins, threaded through the channel in the inner membrane, are handed over to the import motor at the matrix face. Tim17 is an essential, membrane-embedded subunit of the translocase; however, its function is only poorly understood. Here, we functionally dissected its four predicted transmembrane (TM) segments. Mutations in TM1 and TM2 impaired the interaction of Tim17 with Tim23, component of the translocation channel, whereas mutations in TM3 compromised binding of the import motor. We identified residues in the matrix-facing region of Tim17 involved in binding of the import motor. Our results reveal functionally distinct roles of different regions of Tim17 and suggest how they may be involved in handing over the proteins, during their translocation into mitochondria, from the channel to the import motor of the presequence translocase. DOI: http://dx.doi.org/10.7554/eLife.22696.001 PMID:28165323

  10. Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease.

    PubMed

    Li, Xia; Chen, Guojiang; Li, Yurong; Wang, Renxi; Wang, Liyan; Lin, Zhou; Gao, Xudong; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Li, Yan; Han, Gencheng

    2010-02-01

    Augmented intestinal T cells, especially CD4(+)T cells, are involved in the pathogenesis of inflammatory bowel disease (IBD). We used a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model to investigate whether Tim-3, a negative regulator of CD4(+)T cells, is involved in the suppression of IBD. We found that blocking the Tim-3 signal pathway exacerbated TNBS-induced colitis, as shown by increased weight loss and aggravated tissue injury. Blockade of the Tim-3 pathway resulted in an increase in Tim-3(+)CD4T cells, a biased T effector cell response, and a decrease in Treg cells. It also resulted in an altered profile of co-stimulatory molecules expressed on lymphocytes, which partially explained the biased polarization of different T cell subsets. Our data suggest that the Tim-3 pathway is highly involved in the negative regulation of IBD. A better understanding of this pathway may shed new light on the pathogenesis of this disease.

  11. Tim Watkins

    EPA Pesticide Factsheets

    Tim’s expertise and interests lie in the area of air pollution exposure assessment, including ambient air monitoring, personal monitoring, source apportionment, and air quality and exposure modeling.

  12. DAS User Manual

    NASA Astrophysics Data System (ADS)

    Østensen, Roy

    2008-10-01

    The HELAS Database for AsteroSeismology (DAS) is one of the deliverables of the Work Package NA5: Asteroseismology of the European Coordination Action in Helio- and Asteroseismology (HELAS). The DAS aims to provide easy access to publicly available asteroseismological timeseries data, both photometric and spectroscopic. In particular, the DAS and the HELAS software package FAMIAS are ideally suited to train Master and PhD students in asteroseismic data analysis and to build longterm datasets. The number of stars in the system is still limited and reflects the willingness of data owners to provide their data after publication. Work continues to populate the database with contributions from the community, and at present the number of stars in the database is 82

  13. Earth-Mars Telecommunications and Information Management System (TIMS): Antenna Visibility Determination, Network Simulation, and Management Models

    NASA Technical Reports Server (NTRS)

    Odubiyi, Jide; Kocur, David; Pino, Nino; Chu, Don

    1996-01-01

    This report presents the results of our research on Earth-Mars Telecommunications and Information Management System (TIMS) network modeling and unattended network operations. The primary focus of our research is to investigate the feasibility of the TIMS architecture, which links the Earth-based Mars Operations Control Center, Science Data Processing Facility, Mars Network Management Center, and the Deep Space Network of antennae to the relay satellites and other communication network elements based in the Mars region. The investigation was enhanced by developing Build 3 of the TIMS network modeling and simulation model. The results of several 'what-if' scenarios are reported along with reports on upgraded antenna visibility determination software and unattended network management prototype.

  14. Simulation modeling and preliminary analysis of TIMS data from the Carlin area and the northern Grapevine Mountains, Nevada

    NASA Technical Reports Server (NTRS)

    Watson, Ken; Hummer-Miller, Susanne; Kruse, Fred A.

    1986-01-01

    A theoretical radiance model was employed together with laboratory data on a suite of igneous rock to evaluate various algorithms for processing Thermal Infrared Multispectral Scanner (TIMS) data. Two aspects of the general problem were examined: extraction of emissivity information from the observed TIMS radiance data, and how to use emissivity data in a way that is geologically meaningful. The four algorithms were evaluated for appropriate band combinations of TIMS data acquired on both day and night overflights of the Tuscarora Mountains, including the Carlin gold deposit, in north-central Nevada. Analysis of a color composited PC decorrelated image (Bands 3, 4, 5--blue/green/red) of the Northern Grapevine Mountains, Nevada, area showed some useful correlation with the regional geology. The thermal infrared region provides fundamental spectral information that can be used to discriminate the major rock types occurring on the Earth's surface.

  15. Upregulation of T-cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Monocytes/Macrophages Associates with Gastric Cancer Progression.

    PubMed

    Wang, Zhenxin; Yin, Ni; Zhang, Zixiang; Zhang, Yi; Zhang, Guangbo; Chen, Weichang

    2017-02-01

    T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is an important immune regulatory molecule in cancer immune system. However, expression and function of Tim-3 in monocytes/macrophages in cancer progression mainly remain unclear. In this study, we analyzed Tim-3 levels in peripheral blood mononuclear cells (PBMCs) from 62 gastric cancer patients and 45 healthy controls using flow cytometry and then associated Tim-3 levels with clinical pathological data from patients. We found Tim-3 level was significantly upregulated in monocytes from gastric cancer patients compared with those from healthy controls, and that upregulated Tim-3 levels associated with depth of tumor invasion and tumor lymph node metastasis and advanced clinical stages of gastric cancer patients. Furthermore, tumor-bearing mouse experiments revealed that Tim-3 level on monocytes/macrophages associated with xenograft formation and growth. In addition, culture of monocytes from healthy controls with gastric cancer cell-conditioned medium upregulated Tim-3 expression, but IL-10, TNF-α, IFN-γ, or GM-CSF treatment or T-bet, Eomes, and T-bet/Eomes double gene knockout did not affect Tim-3 levels in blood monocytes/macrophages from human or mouse, respectively. Gal-9/Tim-3 signal was able to significantly stimulate monocyte to secrete IL-6, IL-8, and IL-10, but not IL-1β, IL-12p70, or TNF-α in presence of LPS. In conclusion, our study demonstrated that Tim-3 expressed by monocyte/macrophages might be an important mechanism in gastric cancer progression.

  16. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer.

    PubMed

    Shayan, Gulidanna; Srivastava, Raghvendra; Li, Jing; Schmitt, Nicole; Kane, Lawrence P; Ferris, Robert L

    2017-01-01

    Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL. We observed that PD-1 and Tim-3 co-expression was associated with a more exhausted phenotype, with the highest PD-1 levels on TIL co-expressing Tim-3. Dampened Akt/S6 phosphorylation in these PD-1(+)Tim-3(+) TIL, when the PD-1 pathway was ligated, suggested that signaling cross-talk could lead to escape through Tim-3 expression. Indeed, PD-1 blockade of human HNSCC TIL led to further Tim-3 upregulation, supporting a circuit of compensatory signaling and potentially permitting escape from anti-PD-1 blockade in the tumor microenvironment. Also, in a murine HNC tumor model that is partially responsive to anti-PD-1 therapy, Tim-3 was upregulated in TIL from persistently growing tumors. Significant antitumor activity was observed after sequential addition of anti-Tim-3 mAb to overcome adaptive resistance to anti-PD-1 mAb. This increased Tim-3-mediated escape of exhausted TIL from PD-1 inhibition that was mediated by phospho-inositol-3 kinase (PI3K)/Akt complex downstream of TCR signaling but not cytokine-mediated pathways. Taken together, we conclude that during PD-1 blockade, TIL upregulate Tim-3 in a PI3K/Akt-dependent manner, providing further support for dual targeting of these molecules for more effective cancer immunotherapy.

  17. The amelioration of composite tissue allograft rejection by TIM-3-modified dendritic cell: Regulation of the balance of regulatory and effector T cells.

    PubMed

    Wang, Yaojun; Zheng, Zhao; Zhu, Xiongxiang; Han, Juntao; Dong, Maolong; Tao, Ke; Wang, Hongtao; Wang, Yunchuan; Hu, Dahai

    2016-01-01

    T cell-dependent immune responses play a central role in allograft rejection. Exploring ways to disarm alloreactive T cells represents a potential strategy to promote long-term allograft acceptance and survival. T cell Ig domain and mucin domain 3 (TIM-3) has previously been demonstrated as a central regulator of T helper 1 (Th1) responses and immune tolerance. Hence, TIM-3 may be an important molecule for decreasing immunological rejection during composite tissue allotransplantation (CTA). In this study, BALB/c and C57BL/6 mice were chosen as the experimental animals. The effects of TIM-3 on allograft rejection were explored using TIM-3-modified mature dendritic cells (TIM-3 mDCs). A laser speckle blood flow (LSBF) imager was used to evaluate blood distribution of the BALB/c mice. ELISA, MTT, ELISPOT assays and flow cytometry analysis were carried out for further researches. We found that TIM-3 could obviously prolong the survival time of the transplanted limbs. And TIM-3 could mitigate the immune response and thus enhance immune tolerance after CTA. Also, TIM-3 can induce lymphocyte hyporesponsiveness, including facilitating lymphocyte apoptosis, decreasing lymphocyte proliferation, and influencing the secretion of inflammatory cytokines by CD4(+) T cells. Furthermore, TIM-3 overexpression could induce CD4(+) T cells to differentiate into regulatory T cells (Tregs), which recalibrate the effector and regulatory arms of the alloimmune response. In summary, we concluded that TIM-3 can mitigate allograft rejection and thus enhance immune tolerance by inducing lymphocyte hyporesponsiveness and increasing the number of Tregs of the alloimmune response. TIM-3 may be a potential therapeutic molecule for allograft rejection in CTA.

  18. The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas.

    PubMed

    Komohara, Yoshihiro; Morita, Tomoko; Annan, Dorcas A; Horlad, Hasita; Ohnishi, Koji; Yamada, Sohsuke; Nakayama, Toshiyuki; Kitada, Shohei; Suzu, Shinya; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Akashi, Koichi; Takeya, Motohiro; Jinushi, Masahisa

    2015-09-01

    Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204(+) tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14(+) monocytes upon long-term stimulation with RCC cells, and TIM-3-expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti-TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC.

  19. Phlebotomine fauna in the urban area of Timóteo, State of Minas Gerais, Brazil.

    PubMed

    de Souza, Cristian Ferreira; Quaresma, Patrícia Flávia; Andrade Filho, Jose Dilermando; Bevilacqua, Paula Dias

    2014-06-01

    This work is characterized by an entomological research and an investigation on whether seasonal behaviours can be associated to the phlebotomine fauna found in the urban area of Timóteo-MG - an endemic focus of tegumentary leishmaniasis (TL). The analysis of the seasonal behaviour of sand flies has taken into account the following climatic variables: rainfall, relative humidity and temperature. Automatic light traps were installed in households between 2009 and 2010. The sand fly species with the highest number captured was Lutzomyia whitmani (66.5%), a TL vector species, whose abundance has provided strong evidences that this species is the main vector of TL in the municipality of Timóteo, with its cycle of transmission developing in its urban area. Amongst the results observed in the analyses of seasonal behaviour, only temperature conveyed particular association between seasonal occurrence of sand flies and climate variables. The findings of this study may assist the local epidemiological surveillance agency in defining strategies and directing efforts for controlling these insects.

  20. Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.

    PubMed

    Casals, Núria; Gómez-Puertas, Paulino; Pié, Juan; Mir, Cecilia; Roca, Ramón; Puisac, Beatriz; Aledo, Rosa; Clotet, Josep; Menao, Sebastián; Serra, Dolors; Asins, Guillermina; Till, Jacqueline; Elias-Jones, Alun C; Cresto, Juan C; Chamoles, Nestor A; Abdenur, Jose E; Mayatepek, Ertan; Besley, Guy; Valencia, Alfonso; Hegardt, Fausto G

    2003-08-01

    This study describes three novel homozygous missense mutations (S75R, S201Y, and D204N) in the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase gene, which caused 3-hydroxy-3-methylglutaric aciduria in patients from Germany, England, and Argentina. Expression studies in Escherichia coli show that S75R and S201Y substitutions completely abolished the HMG-CoA lyase activity, whereas D204N reduced catalytic efficiency to 6.6% of the wild type. We also propose a three-dimensional model for human HMG-CoA lyase containing a (betaalpha)8 (TIM) barrel structure. The model is supported by the similarity with analogous TIM barrel structures of functionally related proteins, by the localization of catalytic amino acids at the active site, and by the coincidence between the shape of the substrate (HMG-CoA) and the predicted inner cavity. The three novel mutations explain the lack of HMG-CoA lyase activity on the basis of the proposed structure: in S75R and S201Y because the new amino acid residues occlude the substrate cavity, and in D204N because the mutation alters the electrochemical environment of the active site. We also report the localization of all missense mutations reported to date and show that these mutations are located in the beta-sheets around the substrate cavity.

  1. analysis of data from upgraded 2.33 micron TIMS: Example of GEO-CAPE application

    NASA Astrophysics Data System (ADS)

    Kumer, J. B.; Rairden, R. L.; Roche, A. E.; Chatfield, R. B.

    2011-12-01

    The Tropospheric Infrared Mapping Spectrometers (TIMS) were originally developed with support from the NASA ESTO Instrument Incubator program (IIP). These were developed to operate in the spectral regions of the CO overtone and fundamental bands at about 2.33 and 4.67 microns, respectively. In the IIP it was shown these could provide measurements of CO vertical structure, with area coverage rate and spatial resolution that would satisfy GEO-CAPE requirements as laid out in the NRC Decadal Survey report. Since completion of the IIP there has been further internal supported development including but not limited to; (a) deployment of the 2.33 unit on an airship that further developed the case for GEO-CAPE application(see HISE 2011 reference below), and (B) a recent upgrade in the 2.33 micron TIMS performance. In this presentation we describe the upgrade and preliminary data (improved spectral resolution). We describe a retrieval procedure that starts with a trial model that is considerably different than the "truth" atmosphere for which the data were acquired, and modifies the trial model to produce a best fit to the data. The result is a best estimate retrieval of the CO, CH4 and H2O columns. Differences in the trial model temperature vs the truth are accounted for. HISE 2011 reference, click on http://www.opticsinfobase.org/abstract.cfm?URI=HISE-2011-HTuD2 and then click on "View Full Text" .

  2. Enhanced ionization efficiency in TIMS analyses of plutonium and americium using porous ion emitters

    DOE PAGES

    Baruzzini, Matthew L.; Hall, Howard L.; Watrous, Matthew G.; ...

    2016-12-05

    Investigations of enhanced sample utilization in thermal ionization mass spectrometry (TIMS) using porous ion emitter (PIE) techniques for the analyses of trace quantities of americium and plutonium were performed. Repeat ionization efficiency (i.e., the ratio of ions detected to atoms loaded on the filament) measurements were conducted on sample sizes ranging from 10–100 pg for americium and 1–100 pg for plutonium using PIE and traditional (i.e., a single, zone-refined rhenium, flat filament ribbon with a carbon ionization enhancer) TIMS filament sources. When compared to traditional filaments, PIEs exhibited an average boost in ionization efficiency of ~550% for plutonium and ~1100%more » for americium. A maximum average efficiency of 1.09% was observed at a 1 pg plutonium sample loading using PIEs. Supplementary trials were conducted using newly developed platinum PIEs to analyze 10 pg mass loadings of plutonium. As a result, platinum PIEs exhibited an additional ~134% boost in ion yield over standard PIEs and ~736% over traditional filaments at the same sample loading level.« less

  3. Enhanced ionization efficiency in TIMS analyses of plutonium and americium using porous ion emitters

    SciTech Connect

    Baruzzini, Matthew L.; Hall, Howard L.; Watrous, Matthew G.; Spencer, Khalil J.; Stanley, Floyd E.

    2016-12-05

    Investigations of enhanced sample utilization in thermal ionization mass spectrometry (TIMS) using porous ion emitter (PIE) techniques for the analyses of trace quantities of americium and plutonium were performed. Repeat ionization efficiency (i.e., the ratio of ions detected to atoms loaded on the filament) measurements were conducted on sample sizes ranging from 10–100 pg for americium and 1–100 pg for plutonium using PIE and traditional (i.e., a single, zone-refined rhenium, flat filament ribbon with a carbon ionization enhancer) TIMS filament sources. When compared to traditional filaments, PIEs exhibited an average boost in ionization efficiency of ~550% for plutonium and ~1100% for americium. A maximum average efficiency of 1.09% was observed at a 1 pg plutonium sample loading using PIEs. Supplementary trials were conducted using newly developed platinum PIEs to analyze 10 pg mass loadings of plutonium. As a result, platinum PIEs exhibited an additional ~134% boost in ion yield over standard PIEs and ~736% over traditional filaments at the same sample loading level.

  4. TIM-3 Rs10515746 (A/C) and Rs10053538 (C/A) Gene Polymorphisms and Risk of Multiple Sclerosis

    PubMed Central

    YAGHOOBI, Esmat; ABEDIAN, Saeed; BABANI, Omid; IZAD, Maryam

    2016-01-01

    Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by auto-reactive T cells against myelin antigens. T-cell immunoglobulin mucin -3 (TIM-3) is a negative regulator glycoprotein expressed by a range of immune cells, including, Th1 cells, activated CD8+ T cells and in a lower level on Th17 cells. A defect in TIM-3 regulation has been shown in multiple sclerosis patients. In humans, several single nucleotide polymorphisms (SNPs) have been identified in the TIM-3 gene and are associated with inflammatory diseases. The aim of this study was to analyze the association between TIM-3 -574A>C and -1516 C>A SNPs in the promoter region, and susceptibility to MS. Methods: DNA samples from 102 patients and 102 healthy controls were genotyped using RFLP-PCR method. Results: In this case-control study, analysis of the alleles and genotypes revealed a significant higher frequency of C/C and lower frequency of A/C genotypes for -574 locus of TIM-3 gene in MS patients (P=0.0002). We also found that C/C genotype for locus of -1516 increased in MS patients, while A/C genotype decreased (P=0.012). Allele C of -574C/C and -1516 C>A SNPs were also more frequent in MS patients (P=0.036 and 0.0027 respectively). Conclusion: -574 A>C and -1516 C>A SNPs in the promoter region of TIM3 gene may affect the disease susceptibility. PMID:27398337

  5. Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells.

    PubMed

    Xie, Zhijian; Harrison, Scott H; Torti, Suzy V; Torti, Frank M; Han, Jian

    2013-01-01

    Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modeling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS), we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt) receptor, T cell immunoglobulin and mucin domain-2 (TIM-2). The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt (Fe-HFt) was 2.17 pmol per million cells. TIM-2 binding probability with Fe-HFt was 16.6%. An average of 8.5 min was required for the complex of TIM-2 and Fe-HFt to form an endosome. The endosome containing HFt lasted roughly 2 h. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP) and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method.

  6. Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.

    PubMed

    Pawlak, Kevin J; Prasad, Manoj; Thomas, James L; Whittal, Randy M; Bose, Himangshu S

    2011-11-11

    In the adrenals, testes, and ovaries, 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2) catalyzes the conversion of pregnenolone to progesterone and dehydroepiandrostenedione to androstenedione. Alterations in this pathway can have deleterious effects, including sexual development impairment, spontaneous abortion, and breast cancer. 3βHSD2, synthesized in the cytosol, is imported into the inner mitochondrial membrane (IMM) by translocases. Steroidogenesis requires that 3βHSD2 acts as both a dehydrogenase and isomerase. To achieve this dual functionality, 3βHSD2 must undergo a conformational change; however, what triggers that change remains unknown. We propose that 3βHSD2 associates with IMM or outer mitochondrial membrane translocases facing the intermembrane space (IMS) and that this interaction promotes the conformational change needed for full activity. Fractionation assays demonstrate that 3βHSD2 associated with the IMM but did not integrate into the membrane. Through mass spectrometry and Western blotting of mitochondrial complexes and density gradient ultracentrifugation, we show that that 3βHSD2 formed a transient association with the translocases Tim50 and Tom22 and with Tim23. This association occurred primarily through the interaction of Tim50 with the N terminus of 3βHSD2 and contributed to enzymatic activity. Tim50 knockdown inhibited catalysis of dehydroepiandrostenedione to androstenedione and pregnenolone to progesterone. Although Tim50 knockdown decreased 3βHSD2 expression, restoration of expression via proteasome and protease inhibition did not rescue activity. In addition, protein fingerprinting and CD spectroscopy reveal the flexibility of 3βHSD2, a necessary characteristic for forming multiple associations. In summary, Tim50 regulates 3βHSD2 expression and activity, representing a new role for translocases in steroidogenesis.

  7. The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy.

    PubMed

    Li, Yan-Hong; Zhou, Wen-Hui; Tao, Yu; Wang, Song-Cun; Jiang, Yun-Lan; Zhang, Di; Piao, Hai-Lan; Fu, Qiang; Li, Da-Jin; Du, Mei-Rong

    2016-01-01

    Decidual natural killer (dNK) cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) are expressed on over 60% of dNK cells. Tim-3(+) dNK cells display higher interleukin (IL)-4 and lower tumor necrosis factor (TNF)-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 (Gal-9) and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper (Th)2-type cytokines were decreased and Th1-type cytokines were increased in Tim-3(+) but not Tim-3(-) dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.

  8. [A TIM-3/galectin-9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemia progression].

    PubMed

    Kikushige, Yoshikane

    2016-04-01

    Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. We previously reported that the T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the LCS surface in most types of AML. Since only the TIM-3(+), i.e. not the TIM-3(-), fraction of human AML cells can reconstitute human AML in immunodeficient mice, we hypothesized that the TIM-3 has an essential function in maintaining AML LSCs. Herein, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for human AML LSC development. Serum Gal-9 was significantly elevated in primary AML patients and in mice xenografted with human AML. Neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML, as well as Gal-9 ligation of TIM-3 co-activated NF-κB and β-catenin signaling, suggesting that TIM-3 signaling is necessary for LSC self-renewal. Interestingly, identical changes were found to be involved in the progressive transformation of a variety of pre-leukemic disorders into myeloid leukemia. Thus, molecules constituting the TIM-3/Gal-9 autocrine loop are potential therapeutic targets applicable to most types of myeloid leukemia.

  9. PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy.

    PubMed

    Wang, S-C; Li, Y-H; Piao, H-L; Hong, X-W; Zhang, D; Xu, Y-Y; Tao, Y; Wang, Y; Yuan, M-M; Li, D-J; Du, M-R

    2015-05-07

    CD8+ T cells are critical in the balance between fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T cells from decidua greatly outnumbered those from peripheral blood during human early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+ and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co-expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in decidua. This population exhibited high proliferative activity and Th2-type cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in vitro proliferation and Th2-type cytokine production while increased trophoblast killing and IFN-γ producing capacities of CD8+ T cells. Pregnant CBA/J females challenged with Tim-3 and/or PD-1 blocking antibodies were more susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction. Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were significantly impaired in miscarriage. These findings underline the important roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and maintaining normal pregnancy.

  10. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation.

    PubMed

    Xiao, Sheng; Brooks, Craig R; Sobel, Raymond A; Kuchroo, Vijay K

    2015-02-15

    T cell Ig and mucin domain (Tim)-1 identifies IL-10-producing regulatory B cells (Bregs). Mice on the C57BL/6 background harboring a loss-of-function Tim-1 mutant showed progressive loss of IL-10 production in B cells and with age developed severe multiorgan tissue inflammation. We demonstrate that Tim-1 expression and signaling in Bregs are required for optimal production of IL-10. B cells with Tim-1 defects have impaired IL-10 production but increased proinflammatory cytokine production, including IL-1 and IL-6. Tim-1-deficient B cells promote Th1 and Th17 responses but inhibit the generation of regulatory T cells (Foxp3(+) and IL-10-producing type 1 regulatory T cells) and enhance the severity of experimental autoimmune encephalomyelitis. Mechanistically, Tim-1 on Bregs is required for apoptotic cell (AC) binding to Bregs and for AC-induced IL-10 production in Bregs. Treatment with ACs reduces the severity of experimental autoimmune encephalomyelitis in hosts with wild-type but not Tim-1-deficient Bregs. Collectively, these findings suggest that in addition to serving as a marker for identifying IL-10-producing Bregs, Tim-1 is also critical for maintaining self-tolerance by regulating IL-10 production in Bregs.

  11. Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection

    PubMed Central

    Ju, Ying; Hou, Nan; Zhang, Xiaoning; Zhao, Di; Liu, Ying; Wang, Jinjin; Luan, Fang; Shi, Wei; Zhu, Faliang; Sun, Wensheng; Zhang, Lining; Gao, Chengjiang; Gao, Lifen; Liang, Xiaohong; Ma, Chunhong

    2009-01-01

    T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been reported to participate in the pathogenesis of inflammatory diseases. However, whether Tim-3 is involved in hepatitis B virus (HBV) infection remains unknown. Here, we studied the expression and function of Tim-3 in a hydrodynamics-based mouse model of HBV infection. A significant increase of Tim-3 expression on hepatic T lymphocytes, especially on CD8+ T cells, was demonstrated in HBV model mice from day 7 to day 18. After Tim-3 knockdown by specific shRNAs, significantly increased IFN-γ production from hepatic CD8+ T cells in HBV model mice was observed. Very interestingly, we found Tim-3 expression on CD8+ T cells was higher in HBV model mice with higher serum anti-HBs production. Moreover, Tim-3 knockdown influenced anti-HBs production in vivo. Collectively, our data suggested that Tim-3 might act as a potent regulator of antiviral T-cell responses in HBV infection. PMID:19254478

  12. Das DNA-Puzzle

    NASA Astrophysics Data System (ADS)

    Kirchner, Stefan

    Im Jahre 1953 wurde von James Watson und Francis Crick erstmalig der strukturelle Aufbau der sogenannten DNA (Desoxyribonukleinsäure) beschrieben, welche das Erbgut jedes Lebewesens enthält. Der wesentliche Teil des Erbguts wird dabei durch eine sehr lange Folge der vier Basen Adenin (A), Cytosin (C), Guanin (G) und Thymin (T) codiert. Seit einigen Jahren ist es möglich, die Folge der vier Basen zu einer gegebenen DNA zu bestimmen. Biologen bezeichnen diesen Vorgang als Sequenzierung.

  13. Making Sense of Instruction on Fractions when a Student Lacks Necessary Fractional Schemes: The Case of Tim

    ERIC Educational Resources Information Center

    Olive, John; Vomvoridi, Eugenia

    2006-01-01

    This paper critically examines the discrepancies among the pre-requisite fractional concepts assumed by a curricular unit on operations with fractions, the teacher's assumptions about those concepts and a particular student's understanding of fractions. The paper focuses on the case of one student (Tim) in the teacher's 6th grade class who was…

  14. Fluorescence mapping of mitochondrial TIM23 complex reveals a water-facing, substrate-interacting helix surface.

    PubMed

    Alder, Nathan N; Jensen, Robert E; Johnson, Arthur E

    2008-08-08

    Protein translocation across the mitochondrial inner membrane is mediated by the TIM23 complex. While its central component, Tim23, is believed to form a protein-conducting channel, the regions of this subunit that face the imported protein are unknown. To examine Tim23 structure and environment in intact membranes at high resolution, various derivatives, each with a single, environment-sensitive fluorescent probe positioned at a specific site, were assembled into functional TIM23 complexes in active mitochondria and analyzed by multiple spectral techniques. Probes placed sequentially throughout a transmembrane region that was identified by crosslinking as part of the protein-conducting channel revealed an alpha helix in an amphipathic environment. Probes on the aqueous-facing helical surface specifically underwent spectral changes during protein import, and their accessibility to hydrophilic quenching agents is considered in terms of channel gating. This approach has therefore provided an unprecedented view of a translocon channel structure in an intact, fully operational, membrane-embedded complex.

  15. SIMS and TIMS U-Th-Pb Geochronology of Zircon From the Bishop Tuff

    NASA Astrophysics Data System (ADS)

    Ickert, R. B.; Magee, C. W.; Mundil, R.

    2013-12-01

    The mid-Pleistocene Bishop Tuff (Long Valley, California) is one of the largest volume Quaternary volcanic eruptions and has been extensively studied for its physical and chemical characteristics. These data sets have resulted in the Bishop Tuff being described as an 'archetypal' magmatic system. It has also been the subject of multiple geochronological investigations, in particular due to its occurrence just above the Bruhnes-Matuyama geomagnetic reversal, but also for geochemical investigations of the longevity of magmatic systems and the determination of crystal residence times. Published ages for the BT using different isotopic systems and techniques are difficult to reconcile; for example SIMS Pb/U data sets have been interpreted to reflect zircon crystallization over a timescale of 105 years, with a mean crystallization date around 820 Ka, suggesting a protracted magmatic evolution. In contrast, TIMS Pb/U data suggests zircon crystallization over a much shorter period of time, interpreted to be less than 104 years, with the bulk of zircon crystallization occurring in the last few thousand years before eruption. Augmenting these problems are that some new 40Ar/39Ar sanidine dates are >10% older than the youngest population of zircon, yielding a physically impossible reversal of cooling (eruption) and crystallization ages. Here, we present new SHRIMP II U-Th-Pb data and TIMS single-grain and sub-grain analyses of zircon from the Bishop Tuff. Cathodoluminescence imaging reveals similar features described by others - featureless central regions bounded by sector and oscillatory zoned rims. For young zircon such as these, with radiogenic 206Pb concentrations below 0.5ppm, analyses are very sensitive to corrections to common Pb (either introduced in the lab or present as initial Pb in the zircon). The results of 37 single spot SHRIMP analyses, in which central portions of grains were targeted in order to capture the onset of zircon crytsallization, show a range of

  16. Operations Manager Tim Miller checks out software for the Airborne Synthetic Aperature Radar (AIRSAR

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Tim Miller checks out software for the Airborne Synthetic Aperture Radar (AIRSAR). He was the AIRSAR operations manager for NASA's Jet Propulsion Laboratory. The AIRSAR produces imaging data for a range of studies conducted by the DC-8. NASA is using a DC-8 aircraft as a flying science laboratory. The platform aircraft, based at NASA's Dryden Flight Research Center, Edwards, Calif., collects data for many experiments in support of scientific projects serving the world scientific community. Included in this community are NASA, federal, state, academic and foreign investigators. Data gathered by the DC-8 at flight altitude and by remote sensing have been used for scientific studies in archeology, ecology, geography, hydrology, meteorology, oceanography, volcanology, atmospheric chemistry, soil science and biology.

  17. Optimizing separation of iodine from halogen interferences in preparation for TIMS analysis

    SciTech Connect

    Metz, Lori A.; Payne, Rosara F.; Engelmann, Mark D.

    2011-11-28

    Low-level analysis of radioiodine performed by TIMS requires an initial chemical separation from interfering higher electron-affinity halogens. Experiments using 125I and 36Cl tracers have shown that iodide can be selectively oxidized and purged from solution while the chloride remains in the solution. A systematic investigation of the experimental factors that affect the oxidation and transfer of iodine along with the separation of iodide from chloride has been completed. Experimental design was used to determine the optimum experimental conditions by obtaining a better understanding of factor affects and interactions. Factors such as gas purge rate, experiment run time, and oxidant concentration were simultaneously studied in a central composite design of experiments and response surfaces were generated from results. Optimizing experimental factors resulted in improved iodide oxidation and transfer efficiencies, halogen separation, and shorter analysis times.

  18. Comparison of TSI from SORCE TIM with SFO Ground-Based Photometry

    NASA Astrophysics Data System (ADS)

    Chapman, G. A.; Cookson, A. M.; Preminger, D. G.

    2012-02-01

    Total solar irradiance (TSI) measurements have been available from the TIM instrument on the SORCE spacecraft since 2003. We compare TSI data, both 24-h and 6-h averages, with photometric indices from red and K-line images obtained on a daily basis at the San Fernando Observatory (SFO). For 1253 days of data from 2 March 2003 to 5 May 2010 we compare the data in linear multiple regression analyses. The best results come from using two photometric indices, the red and K-line photometric sums, and SORCE TSI 6-h averages interpolated to the SFO time of observation. For this case, we obtain a coefficient of multiple determination, R 2, of 0.9495 and a quiet-Sun irradiance S 0 = 1360.810 ± 0.004 W m-2. These results provide further support for the hypothesis that the quiet Sun is constant over time.

  19. Comparison of preliminary results from Airborne Aster Simulator (AAS) with TIMS data

    NASA Technical Reports Server (NTRS)

    Kannari, Yoshiaki; Mills, Franklin; Watanabe, Hiroshi; Ezaka, Teruya; Narita, Tatsuhiko; Chang, Sheng-Huei

    1992-01-01

    The Japanese Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER), being developed for a NASA EOS-A satellite, will have 3 VNIR, 6 SWIR, and 5 TIR (8-12 micron) bands. An Airborne ASTER Simulator (AAS) was developed for Japan Resources Observation System Organization (JAROS) by the Geophysical Environmental Research Group (GER) Corp. to research surface temperature and emission features in the MWIR/TIR, to simulate ASTER's TIR bands, and to study further possibility of MWIR/TIR bands. ASTER Simulator has 1 VNIR, 3 MWIR (3-5 microns), and 20 (currently 24) TIR bands. Data was collected over 3 sites - Cuprite, Nevada; Long Valley/Mono Lake, California; and Death Valley, California - with simultaneous ground truth measurements. Preliminary data collected by AAS for Cuprite, Nevada is presented and AAS data is compared with Thermal Infrared Multispectral Scanner (TIMS) data.

  20. Urban remote sensing applications: TIMS observations of the City of Scottsdale

    NASA Technical Reports Server (NTRS)

    Christensen, Philip R.; Melendrez, David E.; Anderson, Donald L.; Hamilton, Victoria E.; Wenrich, Melissa L.; Howard, Douglas

    1995-01-01

    A research program has been initiated between Arizona State University and the City of Scottsdale, Arizona to study the potential applications of TIMS (Thermal Infrared Multispectral Scanner) data for urban scene classification, desert environmental assessment, and change detection. This program is part of a long-term effort to integrate remote sensing observations into state and local planning activities to improve decision making and future planning. Specific test sites include a section of the downtown Scottsdale region that has been mapped in very high detail as part of a pilot program to develop an extensive GIS database. This area thus provides excellent time history of the evolution of the city infrastructure, such as the timing and composition of street repavement. A second area of study includes the McDowell intensive study by state and local agencies to assess potential sites for urban development as well as preservation. These activities are of particular relevance as the Phoenix metropolitan area undergoes major expansion into the surrounding desert areas. The objectives of this study in urban areas are aimed at determining potential applications of TIMS data for classifying and assessing land use and surface temperatures. Land use centers on surface impermeability studies for storm runoff assessment and pollution control. These studies focus on determining the areal abundance of urban vegetation and undeveloped soil. Highly experimental applications include assessment and monitoring of pavement condition. Temperature studies focus on determining swimming pool area and temperature for use in monitoring evaporating and urban water consumption. These activities are of particular relevance as the Phoenix metropolitan area undergoes major expansion into the surrounding desert area.

  1. Interplay between Drying and Stability of a TIM Barrel Protein: A Combined Simulation-Experimental Study

    PubMed Central

    Das, Payel; Kapoor, Divya; Halloran, Kevin T.; Zhou, Ruhong; Matthews, C. Robert

    2013-01-01

    Recent molecular dynamics simulations have suggested important roles for nanoscale dewetting on the stability, function, and folding dynamics of proteins. Using a synergistic simulation-experimental approach on the αTS TIM barrel protein, we validate this hypothesis by revealing the occurrence of drying inside hydrophobic amino acid clusters and its manifestation on experimental measures of protein stability and structure. Cavities created within three clusters of branched aliphatic amino acids, isoleucines, leucines and valines (ILV), were found to experience strong water density fluctuations or intermittent dewetting transitions in simulations. Individually substituting 10 residues in the large ILV cluster at the N-terminus with the less hydrophobic alanine showed a weakening or diminishing effect on dewetting that depended on the site of the mutation. Our simulations also demonstrated that replacement of buried leucines with the isosteric and polar asparagine enhanced the wetting of the N- and C-terminal clusters. Experimental results on the stability, secondary structure and compactness of the native and intermediate states for the asparagine variants are consistent with the preferential drying of the large N-terminal cluster in the intermediate. By contrast, the region encompassing the small C-terminal cluster only experiences partial drying in the intermediate and its structure and stability are unaffected by the asparagine substitution. Surprisingly, the structural distortions required to accommodate the replacement of leucine by asparagine in the N-terminal cluster revealed the existence of alternative stable folds in the native basin. This combined simulation-experimental study demonstrates the critical role of drying in hydrophobic ILV clusters to the folding and stability of the αTS TIM barrel. PMID:23293932

  2. Integrated Modeling System for Analysis of Watershed Water Balance: A Case Study in the Tims Branch Watershed, South Carolina

    NASA Astrophysics Data System (ADS)

    Setegn, S. G.; Mahmoudi, M.; Lawrence, A.; Duque, N.

    2015-12-01

    The Applied Research Center at Florida International University (ARC-FIU) is supporting the soil and groundwater remediation efforts of the U.S. Department of Energy (DOE) Savannah River Site (SRS) by developing a surface water model to simulate the hydrology and the fate and transport of contaminants and sediment in the Tims Branch watershed. Hydrological models are useful tool in water and land resource development and decision-making for watershed management. Moreover, simulation of hydrological processes improves understanding of the environmental dynamics and helps to manage and protect water resources and the environment. MIKE SHE, an advanced integrated modeling system is used to simulate the hydrological processes of the Tim Branch watershed with the objective of developing an integrated modeling system to improve understanding of the physical, chemical and biological processes within the Tims Branch watershed. MIKE SHE simulates water flow in the entire land based phase of the hydrological cycle from rainfall to river flow, via various flow processes such as, overland flow, infiltration, evapotranspiration, and groundwater flow. In this study a MIKE SHE model is developed and applied to the Tim branch watershed to study the watershed response to storm events and understand the water balance of the watershed under different climatic and catchment characteristics. The preliminary result of the integrated model indicated that variation in the depth of overland flow highly depend on the amount and distribution of rainfall in the watershed. The ultimate goal of this project is to couple the MIKE SHE and MIKE 11 models to integrate the hydrological component in the land phase of hydrological cycle and stream flow process. The coupled MIKE SHE/MIKE 11 model will further be integrated with an Ecolab module to represent a range of water quality, contaminant transport, and ecological processes with respect to the stream, surface water and groundwater in the Tims

  3. Das Allgemeine Statistische Archiv

    NASA Astrophysics Data System (ADS)

    Rinne, Horst

    Das Allgemeine Statistische Archiv1, nachfolgend kurz Archiv genannt, ist die älteste, ausschließlich der Statistik gewidmete deutschsprachige wissenschaftliche Fachzeitschrift. Sie ist gut zwanzig Jahre älter als die Deutsche Statistische Gesellschaft, zu deren Publikationsorgan sie mit der Gründung der Gesellschaft im Jahre 1911 wurde. Zeitschrift und Gesellschaft blicken auf eine sehr wechselvolle, aber erfolgreiche gemeinsame Geschichte zurück. Die wissenschaftliche Arbeit der Gesellschaft ist im Archiv und seinen Sonderheften für nachfolgende Generationen dokumentiert.

  4. Development of a Novel Antibody-Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1.

    PubMed

    Thomas, Lawrence J; Vitale, Laura; O'Neill, Thomas; Dolnick, Ree Y; Wallace, Paul K; Minderman, Hans; Gergel, Lauren E; Forsberg, Eric M; Boyer, James M; Storey, James R; Pilsmaker, Catherine D; Hammond, Russell A; Widger, Jenifer; Sundarapandiyan, Karuna; Crocker, Andrea; Marsh, Henry C; Keler, Tibor

    2016-12-01

    T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody-drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1-expressing cell lines, but not on TIM-1-negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1-expressing tumors. Mol Cancer Ther; 15(12); 2946-54. ©2016 AACR.

  5. Preferential Tim-3 expression on Treg and CD8(+) T cells, supported by tumor-associated macrophages, is associated with worse prognosis in gastric cancer.

    PubMed

    Shen, Pinying; Yue, Rongxi; Tang, Jiahong; Si, Haige; Shen, Liqun; Guo, Changsheng; Zhang, Lixin; Han, Huaizhong; Song, Haihan K; Zhao, Pengfei; Wang, Ning; Song, Zongchang; Guo, Chunliang

    2016-01-01

    While infection with H. pylori is a strong risk factor for gastric cancer, most H. pylori-colonized individuals, even those with the high-risk CagA(+)VacA(+) strain, remain asymptomatic over their lifetime. We hypothesized that the discordant outcomes were due to differences in the host immune responses. Previously, Tim-3-mediated immune modulation was observed in H. pylori-challenged mice. In this study, we compared Tim-3-related responses in CagA(+)VacA(+) H. pylori-infected asymptomatic individuals and H. pylori-associated gastric adenocarcinoma patients. We showed that compared to H. pylori-uninfected individuals, both H. pylori-infected asymptomatic and gastric cancer patients upregulated Tim-3 overall. However, the Tim-3 upregulation was enriched on Th1 cells in asymptomatic patients and on Treg and CD8(+) T cells in gastric cancer patients, with respective differences in T cell subset functions. In gastric cancer patients, high Tim-3 expression on Treg and CD8(+) T cells, but not on Th1 cells, was associated with worse prognosis. H. pylori-antigen presentation by tumor-associated macrophages upregulated Tim-3 expression more effectively than by blood monocyte-derived macrophages in vitro. The upregulation of Tim-3 in vitro depended on the concentration of H. pylori antigen but not on whether the cells were from asymptomatic or cancer patients. These data suggest that the discrepancy in Tim-3 upregulation in asymptomatic and cancer subjects is induced by cancer but not the other way around. Once gastric cancer is developed, Tim-3 expression is associated with worse prognosis.

  6. The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.

    PubMed

    He, Ping; Tan, De-Li; Liu, Hong-Xiang; Lv, Feng-Lin; Wu, Wei

    2015-04-01

    The short isoform of Rho guanine nucleotide exchange factor ARHGEF5 is known as TIM, which plays diverse roles in, for example, tumorigenesis, neuronal development and Src-induced podosome formation through the activation of its substrates, the Rho family of GTPases. The activation is auto-inhibited by a putative helix N-terminal to the DH domain of TIM, which is stabilized by the intramolecular interaction of C-terminal SH3 domain with a poly-proline sequence between the putative helix and the DH domain. In this study, we systematically investigated the structural basis, energetic landscape and biological implication underlying TIM auto-inhibition by using atomistic molecular dynamics simulations and binding free energy analysis. The computational study revealed that the binding of SH3 domain to poly-proline sequence is the prerequisite for the stabilization of TIM auto-inhibition. Thus, it is suggested that targeting SH3 domain with competitors of the poly-proline sequence would be a promising strategy to relieve the auto-inhibitory state of TIM. In this consideration, we rationally designed a number of peptide aptamers for competitively inhibiting the SH3 domain based on modeled TIM structure and computationally generated data. Peptide binding test and guanine nucleotide exchange analysis solidified that these designed peptides can both bind to the SH3 domain potently and activate TIM-catalyzed RhoA exchange reaction effectively. Interestingly, a positive correlation between the peptide affinity and induced exchange activity was observed. In addition, separate mutation of three conserved residues Pro49, Pro52 and Lys54 - they are required for peptide recognition by SH3 domain -- in a designed peptide to Ala would completely abolish the capability of this peptide activating TIM. All these come together to suggest an intrinsic relationship between peptide binding to SH3 domain and the activation of TIM.

  7. Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection

    PubMed Central

    Dong, Jie; Yang, Xiao-Fei; Wang, Lin-Xu; Wei, Xin; Wang, An-Hui; Hao, Chun-Qiu; Shen, Huan-Jun; Huang, Chang-Xing; Zhang, Ye; Lian, Jian-Qi

    2017-01-01

    T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study. Tim-3 expressions on CD4+ and CD8+ T cells were assessed in response to HBV-encoding antigens, HBV peptide pools, and common γ-chain (γc) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28 directly induced Tim-3 expression on T cells. γc cytokines also drive Tim-3 up-regulations on both CD4+ and CD8+ T cells in patients with chronic HBV infection. However, γc cytokines did not enhance the Tim-3 inductions by either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, γc cytokines-mediated Tim-3 induction could not be abrogated by γc cytokine receptor-neutralizing antibodies. The current results suggested that elevation of Tim-3 expression on T cells could be regulated by both antigen-dependent and -independent manner in patients with chronic HBV infection. The role of γc cytokines in modulation of inhibitory pathway might be evaluated as immunotherapies in humans.

  8. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia.

    PubMed

    Zhou, Qing; Munger, Meghan E; Veenstra, Rachelle G; Weigel, Brenda J; Hirashima, Mitsuomi; Munn, David H; Murphy, William J; Azuma, Miyuki; Anderson, Ana C; Kuchroo, Vijay K; Blazar, Bruce R

    2011-04-28

    Tumor-associated immune suppression can lead to defective T cell-mediated antitumor immunity. Here, we identified a unique phenotype of exhausted T cells in mice with advanced acute myelogenous leukemia (AML). This phenotype is characterized by the coexpression of Tim-3 and PD-1 on CD8(+) T cells in the liver, the major first site of AML metastases. PD-1 and Tim-3 coexpression increased during AML progression. PD-1(+)Tim-3(+) CD8(+) T cells were deficient in their ability to produce IFN-γ, TNF-α, and IL-2 in response to PD-1 ligand (PDL1) and Tim-3 ligand (galectin-9) expressing AML cells. PD-1 knockout (KO), which were partially resistant to AML challenge, up-regulated Tim-3 during AML progression and such Tim-3(+)PD-1- KO CD8(+) T cells had reduced cytokine production. Galectin-9 KO mice were more resistant to AML, which was associated with reduced T-regulatory cell accumulation and a modest induction of PD-1 and Tim-3 expression on CD8(+) T cells. Whereas blocking the PD-1/PDL1 or Tim-3/galectin-9 pathway alone was insufficient to rescue mice from AML lethality, an additive effect was seen in reducing-albeit not eliminating-both tumor burden and lethality when both pathways were blocked. Therefore, combined PD-1/PDL1 and Tim-3/galectin-9 blockade may be beneficial in preventing CD8(+) T-cell exhaustion in patients with hematologic malignancies such as advanced AML.

  9. Upregulation of Tim-3 on CD4(+) T cells is associated with Th1/Th2 imbalance in patients with allergic asthma.

    PubMed

    Tang, Fei; Wang, Fukun; An, Liyun; Wang, Xianling

    2015-01-01

    T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4(+) T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4(+) T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4(+) T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production.

  10. Least destructive sampling of human remains using laser drilling for Sr isotope analysis by TIMS

    NASA Astrophysics Data System (ADS)

    Willmes, Malte; Moffat, Ian; Grün, Rainer; Armstrong, Richard; Kinsley, Les; McMorrow, Linda

    2013-04-01

    Strontium isotope ratios (87Sr/86Sr) measured in ancient human remains can be used to reconstruct migration patterns of ancient human populations. This application is based on the fact that different geologic regions have distinct Sr isotope signatures that are cycled through the soils, plants and rivers, and eventually enter the food cycle. Sr isotope ratios measured in skeletal remains (bones and teeth) reflect the average of dietary Sr that was consumed when the tissue was formed, allowing the investigation of human migration between geologically distinct terrains. The analysis of human remains is always a sensitive topic requiring minimal damage to the sample, while at the same time providing highly precise and accurate results. Samples can be analysed either by solution methods like thermal ionisation mass spectrometry (TIMS), or by in-situ laser ablation MC-ICP-MS. For TIMS a drill is used to extract a small amount of sample, which is then digested in acid and Sr is separated out using ion exchange chromatography. This technique provides highly precise and accurate results, because any isobaric interferences are removed during chemical separation. The drawback is that drilling may cause visible damage to the sample, restricting access to precious human remains. LA-MC-ICP-MS analysis is very fast and nearly destruction free. However, the accuracy and precision of LA-MC-ICP-MS is limited by a number of factors including large instrumental mass discrimination, laser-induced isotopic and elemental fractionations and molecular interferences on 87Sr. Its application thus requires rigorous data reduction, which can introduce significant uncertainties into the analysis. This is especially true for samples with relatively low Sr concentrations such as human teeth (e.g., Woodhead et al., 2005; Horstwood et al., 2008; Vroon et al., 2008). In addition, LA-MC-ICP-MS has traditionally required a flat sample surface, thus an unbroken tooth needs to be cut, which is rather

  11. High precision calcium isotope analysis using 42Ca-48Ca double-spike TIMS technique

    NASA Astrophysics Data System (ADS)

    Feng, L.; Zhou, L.; Gao, S.; Tong, S. Y.; Zhou, M. L.

    2014-12-01

    Double spike techniques are widely used for determining calcium isotopic compositions of natural samples. The most important factor controlling precision of the double spike technique is the choice of appropriate spike isotope pair, the composition of double spikes and the ratio of spike to sample(CSp/CN). We propose an optimal 42Ca-48Ca double spike protocol which yields the best internal precision for calcium isotopic composition determinations among all kinds of spike pairs and various spike compositions and ratios of spike to sample, as predicted by linear error propagation method. It is suggested to use spike composition of 42Ca/(42Ca+48Ca) = 0.44 mol/mol and CSp/(CN+ CSp)= 0.12mol/mol because it takes both advantages of the largest mass dispersion between 42Ca and 48Ca (14%) and lowest spike cost. Spiked samples were purified by pass through homemade micro-column filled with Ca special resin. K, Ti and other interference elements were completely separated, while 100% calcium was recovered with negligible blank. Data collection includes integration time, idle time, focus and peakcenter frequency, which were all carefully designed for the highest internal precision and lowest analysis time. All beams were automatically measured in a sequence by Triton TIMS so as to eliminate difference of analytical conditions between samples and standards, and also to increase the analytical throughputs. The typical internal precision of 100 duty cycles for one beam is 0.012‒0.015 ‰ (2δSEM), which agrees well with the predicted internal precision of 0.0124 ‰ (2δSEM). Our methods improve internal precisions by a factor of 2‒10 compared to previous methods of determination of calcium isotopic compositions by double spike TIMS. We analyzed NIST SRM 915a, NIST SRM 915b and Pacific Seawater as well as interspersed geological samples during two months. The obtained average δ44/40Ca (all relative to NIST SRM 915a) is 0.02 ± 0.02 ‰ (n=28), 0.72±0.04 ‰ (n=10) and 1

  12. Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma

    PubMed Central

    Li, Zhu; Li, Na; Li, Fang; Zhou, Zhihua; Sang, Jiao; Chen, Yanping; Han, Qunying; Lv, Yi; Liu, Zhengwen

    2016-01-01

    Abstract Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis. PD-1 and TIM-3 expression in liver tissues were examined by immunohistochemistry and the genotypes of PD1 rs10204525 and TIM3 rs10053538 polymorphisms were determined using genomic DNA extracted from peripheral blood as template. Both PD-1 and TIM-3 expressions in liver infiltrating lymphocytes of HCC tumor tissues were significantly higher than those in tumor adjacent tissues or cirrhotic tissues. The elevated PD-1 and TIM-3 expressions were significantly associated with higher tumor grades. The levels between PD-1 and TIM-3 expression in tumor tissues and tumor adjacent tissues had a significant positive intercorrelation. The expressions of PD-1 and TIM-3 in tumor tissues, tumor adjacent tissues, and cirrhotic tissues were significantly associated with PD1 and TIM3 polymorphisms, with genotype AA of PD1 rs10204525 and genotypes GT+TT of TIM3 rs10053538 being associated with significantly increased PD-1 and TIM-3 expression, respectively. These findings support the potential to improve the efficiency of immune checkpoint-targeted therapy and reduce resistance to the therapy by blocking both PD-1 and TIM-3 and suggest the potential to apply the genotype determination of PD1 rs10204525 and TIM3 rs10053538 as biomarkers of immune checkpoint-directed therapies. PMID:28033288

  13. Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma.

    PubMed

    Li, Zhu; Li, Na; Li, Fang; Zhou, Zhihua; Sang, Jiao; Chen, Yanping; Han, Qunying; Lv, Yi; Liu, Zhengwen

    2016-12-01

    Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis.PD-1 and TIM-3 expression in liver tissues were examined by immunohistochemistry and the genotypes of PD1 rs10204525 and TIM3 rs10053538 polymorphisms were determined using genomic DNA extracted from peripheral blood as template.Both PD-1 and TIM-3 expressions in liver infiltrating lymphocytes of HCC tumor tissues were significantly higher than those in tumor adjacent tissues or cirrhotic tissues. The elevated PD-1 and TIM-3 expressions were significantly associated with higher tumor grades. The levels between PD-1 and TIM-3 expression in tumor tissues and tumor adjacent tissues had a significant positive intercorrelation. The expressions of PD-1 and TIM-3 in tumor tissues, tumor adjacent tissues, and cirrhotic tissues were significantly associated with PD1 and TIM3 polymorphisms, with genotype AA of PD1 rs10204525 and genotypes GT+TT of TIM3 rs10053538 being associated with significantly increased PD-1 and TIM-3 expression, respectively.These findings support the potential to improve the efficiency of immune checkpoint-targeted therapy and reduce resistance to the therapy by blocking both PD-1 and TIM-3 and suggest the potential to apply the genotype determination of PD1 rs10204525 and TIM3 rs10053538 as biomarkers of immune checkpoint-directed therapies.

  14. Tipin/Tim1/And1 protein complex promotes Pol alpha chromatin binding and sister chromatid cohesion.

    PubMed

    Errico, Alessia; Cosentino, Claudia; Rivera, Teresa; Losada, Ana; Schwob, Etienne; Hunt, Tim; Costanzo, Vincenzo

    2009-12-02

    The Tipin/Tim1 complex plays an important role in the S-phase checkpoint and replication fork stability. However, the biochemical function of this complex is poorly understood. Using Xenopus laevis egg extract we show that Tipin is required for DNA replication in the presence of limiting amount of replication origins. Under these conditions the DNA replication defect correlates with decreased levels of DNA Polalpha on chromatin. We identified And1, a Polalpha chromatin-loading factor, as new Tipin-binding partner. We found that both Tipin and And1 promote stable binding of Polalpha to chromatin and that this is required for DNA replication under unchallenged conditions. Strikingly, extracts lacking Tipin and And1 also show reduced sister chromatids cohesion. These data indicate that Tipin/Tim1/And1 form a complex that links stabilization of replication fork and establishment of sister chromatid cohesion.

  15. Quantitative estimation of granitoid composition from thermal infrared multispectral scanner (TIMS) data, Desolation Wilderness, northern Sierra Nevada, California

    NASA Technical Reports Server (NTRS)

    Sabine, Charles; Realmuto, Vincent J.; Taranik, James V.

    1994-01-01

    We have produced images that quantitatively depict modal and chemical parameters of granitoids using an image processing algorithm called MINMAP that fits Gaussian curves to normalized emittance spectra recovered from thermal infrared multispectral scanner (TIMS) radiance data. We applied the algorithm to TIMS data from the Desolation Wilderness, an extensively glaciated area near the northern end of the Sierra Nevada batholith that is underlain by Jurassic and Cretaceous plutons that range from diorite and anorthosite to leucogranite. The wavelength corresponding to the calculated emittance minimum lambda(sub min) varies linearly with quartz content, SiO2, and other modal and chemical parameters. Thematic maps of quartz and silica content derived from lambda(sub min) values distinguish bodies of diorite from surrounding granite, identify outcrops of anorthosite, and separate felsic, intermediate, and mafic rocks.

  16. TIM Version 3.0 beta Technical Description and User Guide - Appendix D - Avian Data to Support Generic and Custom Species

    EPA Pesticide Factsheets

    TIM Appendix D summarizes avian census studies from pesticide registrant submissions and literature. The purpose of this review is to identify avian species that are representative of those that commonly visit agricultural fields.

  17. TIM Version 3.0 beta Technical Description and User Guide - Appendix B - Example input file for TIMv3.0

    EPA Pesticide Factsheets

    Terrestrial Investigation Model, TIM, has several appendices to its user guide. This is the appendix that includes an example input file in its preserved format. Both parameters and comments defining them are included.

  18. The use of aircraft-based Thermal Infrared Multispectral Scanner (TIMS) data to measure surface energy budgets on a landscape scale

    NASA Technical Reports Server (NTRS)

    Luvall, Jeffrey C.

    1991-01-01

    A series of Thermal Infrared Multispectral Scanner Data (TIMS) was collected over the H. J. Andrews experimental forest in western Oregon and at the Coweeta Hydrologic Laboratory in North Carolina. Flight lines were overlapped with an 8 to 28 minute time difference between flight lines. Concurrent radiosonde measurements of atmospheric profiles of air and dew point temperatures provided inputs to LOWTRAN6 for atmospheric radiance corrections of the TIMS data. Surface temperature differences over time between flight lines allowed the development of thermal response numbers (TRN) which characterized the thermal response of the different surface types. The polygons containing mostly soil and bare rock had the lowest TRN whereas the forested polygons were the highest. Results indicate that forest canopy temperatures measured by the TIMS are comparable to needle thermocouples temperatures. ET models developed from the TIMS data obtained similar ET rates as those using energy balance techniques.

  19. The many Metaphysics within Physics. Essay review of 'The Metaphysics within Physics' by Tim Maudlin

    NASA Astrophysics Data System (ADS)

    Suárez, Mauricio

    Tim Maudlin's new book The Metaphysics within Physics (Oxford University Press, 2007) collects six essays by one of the most thoughtful and original minds working in the philosophy of physics nowadays. Some had previously circulated informally for years. For example, Chapter 1 ('A Modest Proposal Concerning Laws, Counterfactuals and Explanations') is as old as my own philosophical career-I recall reading a draft in the early 1990s. The mere publication of such a long-awaited collection is therefore already good news. In addition, the degree of coherence and the lack of redundancy are greater than one would expect from a collection of disparate essays written at diverse times and with a range of different targets. The whole book can be understood coherently as an extended argument in favor of a particular 'physics-based' methodology for inquiry in metaphysics. This methodology recommends a detailed and thorough analysis of current physics as a benchmark for any thesis, dispute or argument in metaphysics. It follows that proper metaphysical inquiry must be suitably informed not just about the current state of play in analytical metaphysics but also about the current state of development of the relevant part of present day physics.

  20. A Compact, TIM-Based, Pulsed-Power System for Magnetized Target Experiments on OMEGA

    NASA Astrophysics Data System (ADS)

    Gotchev, O. V.; Barbero, M. D.; Jang, N. W.; Knauer, J. P.; Betti, R.

    2006-10-01

    By magnetizing the target and then compressing the magnetic flux to levels sufficient to inhibit thermal transport in the hot spot, one can trigger ignition in massive cryogenic shells imploded with low velocity. The reduction in thermal-conduction losses leads to increased hot-spot temperatures at lower implosion velocities, thus relaxing the energy requirements for ignition. This work describes a compact, pulsed-power system for the generation of a macroscopic seed magnetic field and its integration into such flux-compression experiments on OMEGA. Magnetohydrodynamic simulations predict compression of a 10-T seed field to multimegagauss values. A fast (100-ns) current pulse (up to 60 kA), driven by a TIM-based energy-delivery system, is discharged into a low-mass, double coil that surrounds the laser target. A working prototype has generated a >11-T seed field utilizing a <100-J capacitor bank, laser-triggered spark gap, and a low-impedance (<1-φ) stripline. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-92SF19460. N. W. Jang et al., ``Theory and Simulation of Laser-Driven Magnetic Field Compression,'' this conference.

  1. Characterization of age-associated exhausted CD8⁺ T cells defined by increased expression of Tim-3 and PD-1.

    PubMed

    Lee, Kyoo-A; Shin, Kwang-Soo; Kim, Ga-Young; Song, You Chan; Bae, Eun-Ah; Kim, Il-Kyu; Koh, Choong-Hyun; Kang, Chang-Yuil

    2016-04-01

    Aging is accompanied by altered T-cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD-1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T-cell exhaustion and aging-associated immune dysfunction. In this study, we demonstrate that T-cell immunoglobulin mucin domain-3 (Tim-3), another exhaustion marker, is up-regulated on aged T cells, especially CD8(+) T cells. Tim-3-expressing cells also produced PD-1, but Tim-3(+) PD-1(+) CD8(+) T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim-3(-) PD-1(+) cells. Tim-3(+) PD-1(+) CD8(+) T cells showed more evident properties associated with exhaustion than Tim-3(-) PD-1(+) CD8(+) T cells: an exhaustion-related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL-10 and induced normal CD8(+) T cells to produce IL-10, which might contribute to immune dysregulation in aged mice. The generation of Tim-3-expressing CD8(+) T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8(+) T-cell population with age-associated exhaustion was distinguishable by its expression of Tim-3. These results provide clues for understanding the alterations that occur in T-cell populations with age and for improving dysfunctions related to the aging of the immune system.

  2. Dissection of the gene of the bifunctional PGK-TIM fusion protein from the hyperthermophilic bacterium Thermotoga maritima: design and characterization of the separate triosephosphate isomerase.

    PubMed Central

    Beaucamp, N.; Hofmann, A.; Kellerer, B.; Jaenicke, R.

    1997-01-01

    Triosephosphate isomerase (TIM), from the hyperthermophilic bacterium Thermotoga maritima, has been shown to be covalently linked to phosphoglycerate kinase (PGK) forming a bifunctional fusion protein with TIM as the C-terminal portion of the subunits of the tetrameric protein (Schurig et al., EMBO J 14:442-451, 1995). To study the effect of the anomalous state of association on the structure, stability, and function of Thermotoga TIM, the isolated enzyme was cloned and expressed in Escherichia coli, and compared with its wild-type structure in the PGK-TIM fusion protein. After introducing a start codon at the beginning of the tpi open reading frame, the gene was expressed in E.c.BL21(DE3)/ pNBTIM. The nucleotide sequence was confirmed and the protein purified as a functional dimer of 56.5 kDa molecular mass. Spectral analysis, using absorption, fluorescence emission, near- and far-UV circular dichroism spectroscopy were used to compare the separated Thermotoga enzyme with its homologs from mesophiles. The catalytic properties of the enzyme at approximately 80 degrees C are similar to those of its mesophilic counterparts at their respective physiological temperatures, in accordance with the idea that under in vivo conditions enzymes occupy corresponding states. As taken from chaotropic and thermal denaturation transitions, the separated enzyme exhibits high intrinsic stability, with a half-concentration of guanidinium-chloride at 3.8 M, and a denaturation half-time at 80 degrees C of 2 h. Comparing the properties of the TIM portion of the PGK-TIM fusion protein with those of the isolated recombinant TIM, it is found that the fusion of the two enzymes not only enhances the intrinsic stability of TIM but also its catalytic efficiency. PMID:9336838

  3. MicroRNA-155 regulates interferon-γ production in natural killer cells via Tim-3 signalling in chronic hepatitis C virus infection.

    PubMed

    Cheng, Yong Q; Ren, Jun P; Zhao, Juan; Wang, Jia M; Zhou, Yun; Li, Guang Y; Moorman, Jonathan P; Yao, Zhi Q

    2015-08-01

    Host immune responses must be tightly regulated by an intricate balance between positive and negative signals while fighting pathogens; persistent pathogens may usurp these regulatory mechanisms to dampen host immunity to facilitate survival in vivo. Here we report that Tim-3, a negative signalling molecule expressed on monocytes and T cells, is up-regulated on natural killer (NK) cells in individuals chronically infected with hepatitis C virus (HCV). Additionally, the transcription factor T-bet was also found to be up-regulated and associated with Tim-3 expression in NK cells during chronic HCV infection. MicroRNA-155 (miR-155), an miRNA that inhibits signalling proteins involved in immune responses, was down-regulated in NK cells by HCV infection. This Tim-3/T-bet over-expression and miR-155 inhibition were recapitulated in vitro by incubating primary NK cells or NK92 cell line with Huh-7 hepatocytes expressing HCV. Reconstitution of miR-155 in NK cells from HCV-infected patients led to a decrease in T-bet/Tim-3 expression and an increase in interferon-γ production. Blocking Tim-3 signalling also enhanced interferon-γ production in NK cells by improving signal transducer and activator of transcription-5 phosphorylation. These data indicate that HCV-induced, miR-155-regulated Tim-3 expression regulates NK cell function, suggesting a novel mechanism for balancing immune clearance and immune injury during chronic viral infection.

  4. Connecting the Dots in DAS

    ERIC Educational Resources Information Center

    Ford, Tracy

    2012-01-01

    Many institutions implement a distributed antenna system (DAS) as part of a holistic approach to providing better wireless coverage and capacity on campus. A DAS provides wireless service within a particular area or structure via a network of separate antenna nodes that are connected to a common source through fiber or coaxial cable. Because DAS…

  5. Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9.

    PubMed

    Schwartz, Jordan Ari; Clayton, Kiera L; Mujib, Shariq; Zhang, Hongliang; Rahman, A K M Nur-Ur; Liu, Jun; Yue, Feng Yun; Benko, Erika; Kovacs, Colin; Ostrowski, Mario A

    2017-03-06

    In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG. Thus, Tim-3 may serve as a biomarker of pDC dysfunction in HIV infection. The source and function of Tim-3 was investigated on enriched pDC populations from donors not infected with HIV. Tim-3 induction was achieved in response to viral and artificial stimuli, as well as exogenous IFN-α, and was PI3K dependent. Potent pDC-activating stimuli, such as CpG, imiquimod, and Sendai virus, induced the most Tim-3 expression and subsequent dysfunction. Small interfering RNA knockdown of Tim-3 increased IFN-α secretion in response to activation. Intracellular Tim-3, as measured by confocal microscopy, was dispersed throughout the cytoplasm prior to activation. Postactivation, Tim-3 accumulated at the plasma membrane and associated with disrupted TLR9 at the submembrane. Tim-3-expressing pDCs had reduced IRF7 levels. Furthermore, intracellular Tim-3 colocalized with p85 and IRF7 within LAMP1(+) lysosomes, suggestive of a role in degradation. We conclude that Tim-3 is a biomarker of dysfunctional pDCs and may negatively regulate IFN-α, possibly through interference with TLR signaling and recruitment of IRF7 and p85 into lysosomes, enhancing their degradation.

  6. Uranium and Calcium Isotope Ratio Measurements using the Modified Total Evaporation Method in TIMS

    NASA Astrophysics Data System (ADS)

    Richter, S.; Kuehn, H.; Berglund, M.; Hennessy, C.

    2010-12-01

    A new version of the "modified total evaporation" (MTE) method for isotopic analysis by multi-collector thermal ionization mass spectrometry (TIMS), with high analytical performance and designed in a more user-friendly and routinely applicable way, is described in detail. It is mainly being used for nuclear safeguards measurements of U and Pu and nuclear metrology, but can readily be applied to other scientific tasks in geochemistry, e.g. for Sr, Nd and Ca, as well. The development of the MTE method was organized in collaboration of several "key nuclear mass spectrometry laboratories", namely the New Brunswick Laboratory (NBL), the Institute for Transuranium Elements (ITU), the Safeguards Analytical Laboratory (now Safeguards Analytical Services, SGAS) of the International Atomic Energy Agency (IAEA) and the Institute for Reference Materials and Measurements (IRMM), with IRMM taking the leading role. The manufacturer of the TRITON TIMS instrument, Thermo Fisher Scientific, integrated this method into the software of the instrument. The development has now reached its goal to become a user-friendly and routinely useable method for uranium isotope ratio measurements with high precision and accuracy. Due to the use of the “total evaporation” (TE) method the measurement of the "major" uranium isotope ratio 235U/238U is routinely being performed with a precision of 0.01% to 0.02%. The use of a (certified) reference material measured under comparable conditions is emphasized to achieve an accuracy at a level of 0.02% - depending on the stated uncertainty of the certified value of the reference material. In contrast to the total evaporation method (TE), in the MTE method the total evaporation sequence is interrupted on a regular basis to allow for correction for background from peak tailing, internal calibration of a secondary electron multiplier (SEM) detector versus the Faraday cups, and ion source re-focusing. Therefore, the most significant improvement using the

  7. Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer

    PubMed Central

    2013-01-01

    Background T-cell immunoglobulin and mucin domain 3 (TIM-3) is known as a negative immune regulator and emerging data have implicated TIM-3 a pivotal role in suppressing antitumor immunity. The co-stimulatory receptor CD137 is transiently upregulated on T-cells following activation and increases their proliferation and survival when engaged. Although antagonistic anti-TIM-3 or agonistic anti-CD137 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. In this study, we sought to evaluate whether combined TIM-3 blockade and CD137 activation would significantly improve the immunotherapy in the murine ID8 ovarian cancer model. Methods Mice with established ID8 tumor were intraperitoneally injected with single or combined anti-TIM-3/CD137 monoclonal antibody (mAb); mice survival was recorded, the composition and gene expression of tumor-infiltrating immune cells in these mice was analyzed by flow cytometry and quantitative RT-PCR respectively, and the function of CD8+ cells was evaluated by ELISA and cytotoxicity assay. Results Either anti-TIM-3 or CD137 mAb alone, although effective in 3 days established tumor, was unable to prevent tumor progression in mice bearing 10 days established tumor, however, combined anti-TIM-3/CD137 mAb significantly inhibited the growth of these tumors with 60% of mice tumor free 90 days after tumor inoculation. Therapeutic efficacy was associated with a systemic immune response with memory and antigen specificity, required CD4+ cells and CD8+ cells. The 2 mAb combination increased CD4+ and CD8+ cells and decreased immunosuppressive CD4+FoxP3+ regulatory T (Treg) cells and CD11b+Gr-1+ myeloid suppressor cells (MDSC) at tumor sites, giving rise to significantly elevated ratios of CD4+ and CD8+ cells to Treg and MDSC; This is consistent with biasing local immune response towards an immunostimulatory Th1 type and is further supported by quantitative RT-PCR data

  8. High-Precision Th-Pb Dating by Isotope-Dilution TIMS+MC-ICPMS - Preliminary Results

    NASA Astrophysics Data System (ADS)

    Ickert, R. B.; Mundil, R.; Sharp, W. D.

    2014-12-01

    Relative to the U-Pb decay series, the Th-Pb decay series has received relatively little attention for geochronology although it offers promising applications in both high-resolution geochronology as well as thermochronology. The limitations are partly because Th measurements by thermal ionization have proven notoriously difficult, and for many geochronological applications, the additional information provided by Th-Pb has not been worth the effort required. However, the current generation of MC-ICPMS instruments provides nearly two orders of magnitude better sensitivity of Th than TIMS, eliminating this barrier to measurement and opening up this chronometer for new use. We have developed a method to measure relative abundances of Th, U and Pb by isotope dilution for high-precision geochronology. This method leverages the strengths of two instruments, the high sensitivity and stable mass fractionation of MC-ICPMS instruments for Th and U, and the low background, lack of isobaric interference, and signal stability of TIMS instruments for Pb. To make these measurements, we have calibrated a new synthetic isotope tracer that comprises a mixture of 229Th-233U-236U-202Pb-205Pb. The analytical strategy developed for accessory minerals is a hybrid of techniques previously developed for U-Pb ID-TIMS and U/230Th ID-MC-ICPMS, with a two-column HCl-HNO3 anion exchange procedure (one to separate U and Pb from matrix+Th, and the other to separate Th from matrix), followed by a recombination of the U and Th fractions for MC-ICPMS analysis while the Pb fraction is measured by TIMS. Th-Pb measurements are complementary to, and potentially as precise as the U-Pb gold standard, and the method will find application in certain geological problems, including (1) precisely determining the relative decay rates of 232Th and 238U, (2) dating materials that are young enough to be substantially affected by 230Th or 231Pa disequilibria, and (3) dating small quantities of high-Th minerals like

  9. Genetic variations of PD1 and TIM3 are differentially and interactively associated with the development of cirrhosis and HCC in patients with chronic HBV infection.

    PubMed

    Li, Zhu; Li, Na; Zhu, Qianqian; Zhang, Guoyu; Han, Qunying; Zhang, Pingping; Xun, Meng; Wang, Yawen; Zeng, Xiaoyan; Yang, Cuiling; Liu, Zhengwen

    2013-03-01

    Cooperation or interaction of programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) molecules is more relevant than either molecule alone to immune dysfunction in chronic viral infection and cancers. This study simultaneously investigated polymorphisms at PD1 +8669 and TIM3 -1516 loci in 845 hepatitis B virus (HBV) chronically infected patients [151 asymptomatic carriers, 202 chronic hepatitis, 221 cirrhosis and 271 hepatocellular carcinoma (HCC)], 141 HBV infection resolvers and 318 healthy controls. Multivariate analysis showed that, in addition to gender, age, ALT, albumin and HBV DNA, PD1 +8669 genotype AA was associated with cirrhosis compared with patients without cirrhosis (OR, 2.410; P=0.001). TIM3 -1516 genotypes GT+TT, together with gender, age, ALT, AST, direct bilirubin, albumin and HBeAg status, were associated with HCC compared with cirrhosis patients without HCC (OR, 2.142; P=0.011). The combined carriage of PD1 +8669 AA/TIM3 -1516 GT or TT was higher in cirrhosis and HCC pooled patients than in patients without cirrhosis (OR, 2.326; P=0.020) and in HCC patients than in cirrhosis patients (OR, 2.232; P=0.013). These data suggest that PD1 and TIM3 polymorphisms may differentially and interactively predispose cirrhosis and HCC in chronic HBV infection.

  10. K-feldspar megacrysts growth and their link to the granitic mush: insight from high precision U-Pb dates (ID-TIMS) and trace elements (TIMS-TEA) on zircon

    NASA Astrophysics Data System (ADS)

    Barboni, M.; Schoene, B.

    2012-12-01

    K-feldspar megacrysts are common in granitic to granodioritic rocks though their origin and evolution is still poorly understood. Their occurrence seems to reflect a low nucleation rate relative to growth rate at low degrees of supersaturation. Though K-feldspar has been argued to be one of the last minerals to saturate in felsic magma, crystal mush may still contain 60-70% liquid at the initiation of crystallization. Therefore, abundant liquid might be available for development of large crystals early in the magma cooling process. The recent recognition that many granitoid plutons are built incrementally by many magma injections open new perspectives for K-feldspar megacrysts formation. Repeated replenishment, reheating and reinvigoration of the mush might play a significant role in making and preserving K-feldspar megacrysts. The Miocene Elba island intrusives (Italy) are famous for having some of the largest K-feldspar megacrysts ever found (up to 25 cm.). This young plutonic body emplaced incrementally at shallow crustal level (ca. 3km) and displays extensive evidence of interactions between magmas of contrasting compositions. We have sampled three different families of K-feldspar megacrysts occurring in different host rock and have combined U/Pb high precision dates (ID-TIMS) with trace elements (TIMS-TEA) and Hf isotopes of zircons that are included within the K-feldspar megacrysts and compared them to zircons from the host rock. Ages of zircon included in the megacrysts could document whether the crystals grew early in the magmatic system (inclusions older than the host rock) or late during the cooling history (similar ages within inclusions and host rock). Ti-in zircon thermometer combined with trace-elements signature could record slight differences between megacrysts and host rock zircons, documenting the development of the megacrysts in comparison with the one of the host granite. Strong field evidence support a magmatic/ phenocrystic origin for the Elba

  11. Aerolian erosion, transport, and deposition of volcaniclastic sands among the shifting sand dunes, Christmas Lake Valley, Oregon: TIMS image analysis

    NASA Technical Reports Server (NTRS)

    Edgett, Kenneth S.; Ramsey, Michael S.; Christensen, Philip R.

    1995-01-01

    Remote sensing is a tool that, in the context of aeolian studies, offers a synoptic view of a dune field, sand sea, or entire desert region. Blount et al. (1990) presented one of the first studies demonstrating the power of multispectral images for interpreting the dynamic history of an aeolian sand sea. Blount's work on the Gran Desierto of Mexico used a Landsat TM scene and a linear spectral mixing model to show where different sand populations occur and along what paths these sands may have traveled before becoming incorporated into dunes. Interpretation of sand transport paths and sources in the Gran Desierto led to an improved understanding of the origin and Holocene history of the dunes. With the anticipated advent of the EOS-A platform and ASTER thermal infrared capability in 1998, it will become possible to look at continental sand seas and map sand transport paths using 8-12 mu m bands that are well-suited to tracking silicate sediments. A logical extension of Blount's work is to attempt a similar study using thermal infrared images. One such study has already begun by looking at feldspar, quartz, magnetite, and clay distributions in the Kelso Dunes of southern California. This paper describes the geology and application of TIMS image analysis of a less-well known Holocene dune field in south central Oregon using TIMS data obtained in 1991.

  12. Kinetic Intermediates of Holo- and Apo-Myoglobin Studied Using HDX-TIMS-MS and Molecular Dynamic Simulations

    NASA Astrophysics Data System (ADS)

    Schenk, Emily R.; Almeida, Raybel; Miksovska, Jaroslava; Ridgeway, Mark E.; Park, Melvin A.; Fernandez-Lima, Francisco

    2015-04-01

    In the present work, the kinetic intermediates of holo- and apo-myoglobin were studied by correlating the ion-neutral collision cross section and time resolved H/D back exchange rate simultaneously in a trapped ion mobility spectrometer coupled to a mass spectrometer (HDX-TIMS-MS). The high mobility resolution of the TIMS cell permitted the observation of multiple IMS bands and complementary molecular dynamics simulations resulted in the assignment of candidate structures for each experimental condition studied (e.g., holo [M + 8H]+8-[M + 9H]+9 and apo [M + 9H]+9-[M + 19H]+19). Inspection of the kinetic intermediates suggests that the tertiary structure of apomyoglobin unfolds quickly upon the loss of the Fe protoporphyrin IX that stabilizes the interactions between the A, G, and H helices. In the absence of the porphyrin heme, the apomyoglobin unfolds to Xn kinetic intermediates that vary in the extent of unfolding as a result of the observed charge state.

  13. Mini-DIAL system measurements coupled with multivariate data analysis to identify TIC and TIM simulants: preliminary absorption database analysis.

    NASA Astrophysics Data System (ADS)

    Gaudio, P.; Malizia, A.; Gelfusa, M.; Martinelli, E.; Di Natale, C.; Poggi, L. A.; Bellecci, C.

    2017-01-01

    Nowadays Toxic Industrial Components (TICs) and Toxic Industrial Materials (TIMs) are one of the most dangerous and diffuse vehicle of contamination in urban and industrial areas. The academic world together with the industrial and military one are working on innovative solutions to monitor the diffusion in atmosphere of such pollutants. In this phase the most common commercial sensors are based on “point detection” technology but it is clear that such instruments cannot satisfy the needs of the smart cities. The new challenge is developing stand-off systems to continuously monitor the atmosphere. Quantum Electronics and Plasma Physics (QEP) research group has a long experience in laser system development and has built two demonstrators based on DIAL (Differential Absorption of Light) technology could be able to identify chemical agents in atmosphere. In this work the authors will present one of those DIAL system, the miniaturized one, together with the preliminary results of an experimental campaign conducted on TICs and TIMs simulants in cell with aim of use the absorption database for the further atmospheric an analysis using the same DIAL system. The experimental results are analysed with standard multivariate data analysis technique as Principal Component Analysis (PCA) to develop a classification model aimed at identifying organic chemical compound in atmosphere. The preliminary results of absorption coefficients of some chemical compound are shown together pre PCA analysis.

  14. Tumor antigen-specific CD8(+) T cells are negatively regulated by PD-1 and Tim-3 in human gastric cancer.

    PubMed

    Lu, Xu; Yang, Lin; Yao, Daxing; Wu, Xuan; Li, Jingpo; Liu, Xuesong; Deng, Lijuan; Huang, Caiting; Wang, Yue; Li, Dan; Liu, Jingwei

    2017-03-01

    Cytotoxic CD8 T lymphocytes that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally important in eliciting tumor rejection. NY-ESO-1 is a major target of CD8(+) T cell recognition in gastric cancer (GC) and is among the most immunogenic tumor antigens defined to date. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T cell dysfunction may reveal effective strategies for immunotherapy. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) of GC patients. Here, we report that Tim-3 expression defines a subpopulation of PD-1(+) exhausted NY-ESO-1-specific CD8(+) T cell and PD-1(+)Tim-3(+) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in GC patients. Functionally, CD8(+)PD-1(+)Tim-3(+) T cells were more impaired in IFN-γ, TNF-α and IL-2 production compared with PD-1(+)Tim-3(-) or PD-1(-)Tim-3(-) subsets. Dual blockade of Tim-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1-specific CD8(+) T cells could potentially be improved by therapeutic targeting of these inhibitory receptors, indicating that antitumor function of NY-ESO-1-specific CD8(+) T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.

  15. MyDas, an extensible Java DAS server.

    PubMed

    Salazar, Gustavo A; García, Leyla J; Jones, Philip; Jimenez, Rafael C; Quinn, Antony F; Jenkinson, Andrew M; Mulder, Nicola; Martin, Maria; Hunter, Sarah; Hermjakob, Henning

    2012-01-01

    A large number of diverse, complex, and distributed data resources are currently available in the Bioinformatics domain. The pace of discovery and the diversity of information means that centralised reference databases like UniProt and Ensembl cannot integrate all potentially relevant information sources. From a user perspective however, centralised access to all relevant information concerning a specific query is essential. The Distributed Annotation System (DAS) defines a communication protocol to exchange annotations on genomic and protein sequences; this standardisation enables clients to retrieve data from a myriad of sources, thus offering centralised access to end-users.We introduce MyDas, a web server that facilitates the publishing of biological annotations according to the DAS specification. It deals with the common functionality requirements of making data available, while also providing an extension mechanism in order to implement the specifics of data store interaction. MyDas allows the user to define where the required information is located along with its structure, and is then responsible for the communication protocol details.

  16. High-Precision Isotope Analysis of Uranium and Thorium by TIMS

    NASA Astrophysics Data System (ADS)

    Neymark, L. A.; Paces, J. B.

    2006-12-01

    The U.S. Geological Survey (USGS) Yucca Mountain Project Branch laboratory in Denver, Colorado, conducts routine high-precision isotope analyses of uranium (U) and thorium (Th) using thermal ionization mass- spectrometry (TIMS). The measurements are conducted by a ThermoFinnigan Triton\\texttrademark equipped with a Faraday multi-collector system and an energy filter in front of an active-film-type secondary electron multiplier (SEM). The abundance sensitivity of the instrument (signal at mass 237 over 238U in natural U) with the energy filter is about 15 ppb and peak tails are reduced by a factor of about 100 relative to the Faraday cup measurements. Since instrument installation in April 2004, more than 500 rock and water samples have been analyzed in support of isotope-geochemical studies for the U.S. Department of Energy`s Yucca Mountain Project. Isotope ratios of sub-nanogram to microgram U and Th samples are measured on graphite-coated single- filament and double-filament assemblies using zone-refined rhenium filaments. Ion beams less than 5 mV are measured with the SEM, which is corrected for non-linearity on the basis of measurements of NIST U-500 and 4321B standards with ion beams ranging from 0.01 to 8 mV. Inter-calibration between the SEM and the Faraday multi-collector is performed for every mass cycle using a 5 mV beam switched between Faraday cup and SEM (bridging technique), because SEM-Faraday inter-calibrations prior to the measurement failed to produce acceptable results. Either natural (^{235}U) or artificial (^{236}U, ^{229}Th) isotopes were used for the bridging. Separate runs are conducted for minor isotopes using SEM only. These techniques result in high within-run precisions of less than 0.1 to 0.2 percent for 234U/238U and 0.2 to 0.5 percent for 230Th/238U. The performance of the instrument is monitored using several U and Th isotope standards. The mean measured 234U/238U in NIST SRM 4321B is (52.879±0.004)×10-6 (95 percent confidence, n

  17. Constructing and Deconstructing Giftedness: A Reflective Conversation between Tim Dracup, Architect of England's National Gifted and Talented Education Programme from 1996 to 2009, and Barry Hymer, Professor of Psychology in Education, University of Cumbria, UK

    ERIC Educational Resources Information Center

    Hymer, Barry

    2014-01-01

    This conversation was prompted by a blog entry posted by Tim Dracup in January 2012. The subsequent e-exchange between Tim and Barry Hymer explored a number of issues central to the nature and aetiology of giftedness, confronting these issues from contrasting ontological and epistemological stances. As a result, their conversation includes…

  18. Tim-3 alters the balance of IL-12/IL-23 and drives TH17 cells: role in hepatitis B vaccine failure during hepatitis C infection

    PubMed Central

    Wang, Jia M.; Ma, Cheng J.; Li, Guang Y.; Wu, Xiao Y.; Thayer, Penny; Greer, Pamela; Smith, Ashley M.; High, Kevin P.; Moorman, Jonathan P; Yao, Zhi Q.

    2013-01-01

    Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production with in turn TH17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection. PMID:23499521

  19. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

    PubMed Central

    Schneider, H C; Westermann, B; Neupert, W; Brunner, M

    1996-01-01

    Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

  20. Geologic mapping in Death Valley, California/Nevada using NASA/JPL airborne systems (AVIRIS, TIMS, and AIRSAR)

    NASA Technical Reports Server (NTRS)

    Kruse, Fred A.; Dietz, John B.; Kiereinyoung, Kathryn S.

    1991-01-01

    A multi-sensor aircraft campaign called the Geologic Remote Sensing Field Experiment (GRSFE) conducted during 1989 resulted in acquisition of high quality multispectral images in the visible, near infrared, shortwave infrared, thermal infrared, and microwave regions of the electromagnetic spectrum. The airborne data sets include the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS), the Thermal Infrared Multispectral Scanner (TIMS), and the Airborne Synthetic Aperture Radar (SAR). Ancillary data include Landsat Thematic Mapper, laboratory and field spectral measurements, and traditional geologic mapping. The GRSFE data for a site in the northern Death Valley, (California and Nevada) region were calibrated to physical units and geometrically registered to a map base. Various aspects of this experiment are briefly discussed.

  1. TinyTim modeling of NICMOS PSF subtraction: effects of focus breathing, cold mask wiggling, and color variations

    NASA Astrophysics Data System (ADS)

    Suchkov, A.; Krist, J.

    1998-11-01

    We conduct TinyTim modeling of NICMOS camera 2 PSFs to assess limits to the accuracy of PSF subtraction imposed by color dependence, OTA focus breathing, and cold mask wiggling. The results suggest that effects of both cold mask wiggling and focus breathing can be described as a noise in a PSF-subtracted image, well above 20% of the PSF signal in narrow band filters, with a spatial scale of a few pixels. The main effect of the PSF color dependence is adding a systemic component to the PSF subtracted image. The effect is quite large if the color of the PSF used for subtraction is very different from the image PSF color. It is pronounced in blue, wide filters, like F110W, while in filters like F187W or redder/ narrower it is essentially negligible.

  2. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer

    SciTech Connect

    Heon, Elise K.; Wulan, Hasi; Macdonald, Loch P.; Malek, Adel O.; Braunstein, Glenn H.; Eaves, Connie G.; Schattner, Mark D.; Allen, Peter M.; Alexander, Michael O.; Hawkins, Cynthia A.; McGovern, Dermot W.; Freeman, Richard L.; Amir, Eitan P.; Huse, Jason D.; Zaltzman, Jeffrey S.; Kauff, Noah P.; Meyers, Paul G.; Gleason, Michelle H.; Overholtzer, Michael G.; Wiseman, Sam S.; and others

    2015-08-14

    IL-15 has pivotal roles in the control of CD8{sup +} memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. - Highlights: • We explored the effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells of breast cancer. • IL-15

  3. Chemical Analysis of Water-accommodated Fractions of Crude Oil Spills Using TIMS-FT-ICR MS.

    PubMed

    Benigni, Paolo; Marin, Rebecca; Sandoval, Kathia; Gardinali, Piero; Fernandez-Lima, Francisco

    2017-03-03

    Multiple chemical processes control how crude oil is incorporated into seawater and also the chemical reactions that occur overtime. Studying this system requires the careful preparation of the sample in order to accurately replicate the natural formation of the water-accommodated fraction that occurs in nature. Low-energy water-accommodated fractions (LEWAF) are carefully prepared by mixing crude oil and water at a set ratio. Aspirator bottles are then irradiated, and at set time points, the water is sampled and extracted using standard techniques. A second challenge is the representative characterization of the sample, which must take into consideration the chemical changes that occur over time. A targeted analysis of the aromatic fraction of the LEWAF can be performed using an atmospheric-pressure laser ionization source coupled to a custom-built trapped ion mobility spectrometry-Fourier transform-ion cyclotron resonance mass spectrometer (TIMS-FT-ICR MS). The TIMS-FT-ICR MS analysis provides high-resolution ion mobility and ultrahigh-resolution MS analysis, which further allow the identification of isomeric components by their collision cross-sections (CCS) and chemical formula. Results show that as the oil-water mixture is exposed to light, there is significant photo-solubilization of the surface oil into the water. Over time, the chemical transformation of the solubilized molecules takes place, with a decrease in the number of identifications of nitrogen- and sulfur-bearing species in favor of those with a greater oxygen content than were typically observed in the base oil.

  4. Analysis of Mammalian Sphingolipids by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and Tissue Imaging Mass Spectrometry (TIMS)

    PubMed Central

    Sullards, M. Cameron; Liu, Ying; Chen, Yanfeng; Merrill, Alfred H.

    2011-01-01

    Sphingolipids are a highly diverse category of molecules that serve not only as components of biological structures but also as regulators of numerous cell functions. Because so many of the structural features of sphingolipids give rise to their biological activity, there is a need for comprehensive or “sphingolipidomic” methods for identification and quantitation of as many individual subspecies as possible. This review defines sphingolipids as a class, briefly discusses classical methods for their analysis, and focuses primarily on liquid chromatography tandem mass spectrometry (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). Recently, a set of evolving and expanding methods have been developed and rigorously validated for the extraction, identification, separation, and quantitation of sphingolipids by LC-MS/MS. Quantitation of these biomolecules is made possible via the use of an internal standard cocktail. The compounds that can be readily analyzed are free long-chain (sphingoid) bases, sphingoid base 1-phosphates, and more complex species such as ceramides, ceramide 1-phosphates, sphingomyelins, mono- and di-hexosylceramides sulfatides, and novel compounds such as the 1-deoxy- and 1-(deoxymethyl)-sphingoid bases and their N-acyl-derivatives. These methods can be altered slightly to separate and quantitate isomeric species such as glucosyl/galactosylceramide. Because these techniques require the extraction of sphingolipids from their native environment, any information regarding their localization in histological slices is lost. Therefore, this review also describes methods for TIMS. This technique has been shown to be a powerful tool to determine the localization of individual molecular species of sphingolipids directly from tissue slices. PMID:21749933

  5. Between-species variation in the kinetic stability of TIM proteins linked to solvation-barrier free energies.

    PubMed

    Costas, Miguel; Rodríguez-Larrea, David; De Maria, Leonardo; Borchert, Torben V; Gómez-Puyou, Armando; Sanchez-Ruiz, Jose M

    2009-01-23

    Theoretical, computational, and experimental studies have suggested the existence of solvation barriers in protein unfolding and denaturation processes. These barriers are related to the finite size of water molecules and can be envisioned as arising from the asynchrony between water penetration and breakup of internal interactions. Solvation barriers have been proposed to play roles in protein cooperativity and kinetic stability; therefore, they may be expected to be subject to natural selection. We study the thermal denaturation, in the presence and in the absence of chemical denaturants, of triosephosphate isomerases (TIMs) from three different species: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania mexicana. In all cases, denaturation was irreversible and kinetically controlled. Surprisingly, however, we found large differences between the kinetic denaturation parameters, with T. cruzi TIM showing a much larger activation energy value (and, consequently, much lower room-temperature, extrapolated denaturation rates). This disparity cannot be accounted for by variations in the degree of exposure to solvent in transition states (as measured by kinetic urea m values) and is, therefore, to be attributed mainly to differences in solvation-barrier contributions. This was supported by structure-energetics analyses of the transition states and by application of a novel procedure to estimate from experimental data the solvation-barrier impact at the entropy and free-energy levels. These analyses were actually performed with an extended protein set (including six small proteins plus seven variants of lipase from Thermomyces lanuginosus and spanning a wide range of activation parameters), allowing us to delineate the general trends of the solvation-barrier contributions. Overall, this work supports that proteins sharing the same structure and function but belonging to different organisms may show widely different solvation barriers, possibly as a result of different

  6. HCV-specific T cells in HCV/HIV co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression.

    PubMed

    Vali, Bahareh; Jones, R Brad; Sakhdari, Ali; Sheth, Prameet M; Clayton, Kiera; Yue, Feng-Yun; Gyenes, Gabor; Wong, David; Klein, Marina B; Saeed, Sahar; Benko, Erika; Kovacs, Colin; Kaul, Rupert; Ostrowski, Mario A

    2010-09-01

    Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.

  7. PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8+ T cells induced by melanoma vaccines

    PubMed Central

    Fourcade, Julien; Sun, Zhaojun; Pagliano, Ornella; Chauvin, Joe-Marc; Sander, Cindy; Janjic, Bratislav; Tarhini, Ahmad A.; Tawbi, Hussein A.; Kirkwood, John M.; Moschos, Stergios; Wang, Hong; Guillaume, Philippe; Luescher, Immanuel F.; Krieg, Arthur; Anderson, Ana C.; Kuchroo, Vijay K.; Zarour, Hassane M.

    2014-01-01

    Although melanoma vaccines stimulate tumor antigen (TA)-specific CD8+ T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8+ T cells with regard to the inhibitory T cell co-receptors PD-1 and Tim-3 in metastatic melanoma patients who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant (IFA), CpG oligodeoxynucleotide (CpG) and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid TA-specific CD8+ T-cell responses detected ex vivo, however, TA-specific CD8+ T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8+ T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8+ T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8+ T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T cell responses and increase the likelihood of clinical responses in advanced melanoma patients. PMID:24343228

  8. Better U-Pb Zircon Standards for SIMS and LA-ICPMS? Preliminary Results of Detailed Characterization and Pre-treatment using CA-TIMS

    NASA Astrophysics Data System (ADS)

    Mattinson, J. M.; Hourigan, J.; Wooden, J. L.

    2006-12-01

    U-Pb zircon dating using SIMS and LA-ICPMS requires calibrations against natural zircons of known age. Ideally, such zircons should be perfectly concordant -- free from Pb-loss, inheritance, or any other complications, and also accurately dated. In practice this can be problematic. Complexities can be difficult to detect by SIMS and LA-ICPMS analysis if they are at or below the level of precision of an individual analysis. In addition, conventional TIMS dating, used to date the standards, can be limited by residual minor Pb loss that has not been removed by conventional "pretreatments" such as air abrasion. CA-TIMS (Mattinson, 2005, Chem Geol 220, 47-66) utilizes high-T annealing of natural radiation damage, followed by partial dissolution in HF, and has proven highly successful at complete removal of zircon domains that have experienced Pb loss, both from the outer rims and also from the deep interiors of zircon grains. Thus, it is useful for detailed characterization of existing and potential zircon standards. Here, we also investigate the potential of CA-TIMS for pre-treating zircon standards prior to SIMS and LA-ICPMS analysis. Multi-step CA-TIMS analyses of Temora-2, R-33, and a possible new standard from the Klamath Mountains reveal minor Pb loss in the first few partial dissolution steps, then yield excellent 206Pb*/238 plateau ages, and concordant 207Pb*/206Pb* ages for the remaining steps. Additional aliquots of these zircons were then "pretreated" by CA-TIMS, with sufficient partial dissolution to remove all vestiges of Pb loss, based on the earlier experiments. A sample of AS-57 was pre-treated "blind" because it was received just prior to a scheduled SHRIMP session. All samples were then prepared in a single mount for SHRIMP analysis. Our preliminary results from a round-robin Stanford SHRIMP-RG session using Temora-2, R-33, AS-57, and the Klamath sample are very promising. The Temora-2 and Klamath zircons in particular yielded excellent reproducibility

  9. Mineralogic variability of the Kelso Dunes, Mojave Desert, California derived from Thermal Infrared Multispectral Scanner (TIMS) data

    NASA Technical Reports Server (NTRS)

    Ramsey, Michael S.; Howard, Douglas A.; Christensen, Philip R.; Lancaster, Nicholas

    1993-01-01

    Mineral identification and mapping of alluvial material using thermal infrared (TIR) remote sensing is extremely useful for tracking sediment transport, assessing the degree of weathering and locating sediment sources. As a result of the linear relation between a mineral's percentage in a given area (image pixel) and the depth of its diagnostic spectral features, TIR spectra can be deconvolved in order to ascertain mineralogic percentages. Typical complications such as vegetation, particle size and thermal shadowing are minimized upon examination of dunes. Actively saltating dunes contain little to no vegetation, are very well sorted and lack the thermal shadows that arise from rocky terrain. The primary focus of this work was to use the Kelso Dunes as a test location for an accuracy analysis of temperature/emissivity separation and linear unmixing algorithms. Accurate determination of ground temperature and component discrimination will become key products of future ASTER data. A decorrelation stretch of the TIMS image showed clear color variations within the active dunes. Samples collected from these color units were analyzed for mineralogy, grain size, and separated into endmembers. This analysis not only revealed that the dunes contained significant mineralogic variation, but were more immature (low quartz percentage) than previously reported. Unmixing of the TIMS data using the primary mineral endmembers produced unique variations within the dunes and may indicate near, rather than far, source locales for the dunes. The Kelso Dunes lie in the eastern Mojave Desert, California, approximately 95 km west of the Colorado River. The primary dune field is contained within a topographic basin bounded by the Providence, Granite Mountains, with the active region marked by three northeast trending linear ridges. Although active, the dunes appear to lie at an opposing regional wind boundary which produces little net movement of the crests. Previous studies have estimated

  10. The Southern Urals Large Igneous Province with an age of approximately 1380 Ma: Precision U-Pb ID-TIMS constraints

    NASA Astrophysics Data System (ADS)

    Ronkin, Yu. L.; Tichomirowa, M.; Maslov, A. V.

    2016-06-01

    The formation of the Large Igneous Province (LIP) approximately 1380 Ma old in the South Urals was related to the Mashak riftogenic event in the Bashkir meganticlinorium, which was synchronous with the emplacement of different magmatic bodies (the Berdyaush pluton of rapakivi granites and associated rocks, the Main dike of the Bakal ore field, and the Medvedev, Guben, and Kusa massifs, among others) localized among sedimentary deposits of the Burzyan and Yurmatin Groups representing Lower and Middle Riphean type units of northern Eurasia. The U-Pb ID-TIMS age of 1379.6 Ma (MSWD = 1.3) obtained with an accuracy of ±2.9 Ma (confidence interval 95%) combined with the available published U-Pb ID-TIMS data constrain the age and duration of the Early-Middle Riphean pulse in the LIP formation in the Southern Urals.

  11. Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

    PubMed

    Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

    2016-12-01

    Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (Cm of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (Tm of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement.

  12. Evaluation of GO_CONS_GCF_2_TIM and GOCO01S Geopotential Models in Venezuela and Caribbean Region

    NASA Astrophysics Data System (ADS)

    Orihuela, N. D.; Garcia, A. D.; Tabare, T.; Scientific Team Of Venezuelan; Caribbean Crustal Study From Satellital Data

    2010-12-01

    This paper shows two maps of the magnitude of the surface gravity vector (MSGV) of Venezuela and Caribbean region at 1:500.000 scale in the geographic window between the 0-20 north latitude and 74-58 western longitude (Fig. 1 and Fig. 2), that were generated from GOCE gravity gradients data provided by the European Space Agency (ESA). The maps that are showed come from the combined global gravity field model GOCO01s [GOCO Consortium., 2010] and from the satellite-only global gravity field model GO_CONS_GCF_2_TIM [Pail et al., 2010], both of 224 degree. The DEMs used for the evaluation of the MSGV are: Etopo2v2 [NGDC., 2006] and Etopo1 [Amante and Eakins, 2009] respectively. The data processing was done using: Shm2func [ICGEM., 2007]; Goce User Toolbox [ESA., 2009]; Gravsoft package [Tscherning et al., 1992] and Oasis Montaj (Geosoft). This research shows a review of observed gravity in the main geological provinces of the Venezuela and Caribbean region geography, revealing gravitational features important of the geological structures that are in Venezuelan and Caribbean subsurface.

  13. KIM-1-/TIM-1-mediated phagocytosis links ATG5-/ULK1-dependent clearance of apoptotic cells to antigen presentation

    PubMed Central

    Brooks, Craig R; Yeung, Melissa Y; Brooks, Yang S; Chen, Hui; Ichimura, Takaharu; Henderson, Joel M; Bonventre, Joseph V

    2015-01-01

    Phagocytosis of apoptotic cells by both professional and semi-professional phagocytes is required for resolution of organ damage and maintenance of immune tolerance. KIM-1/TIM-1 is a phosphatidylserine receptor that is expressed on epithelial cells and can transform the cells into phagocytes. Here, we demonstrate that KIM-1 phosphorylation and association with p85 results in encapsulation of phagosomes by lipidated LC3 in multi-membrane organelles. KIM-1-mediated phagocytosis is not associated with increased ROS production, and NOX inhibition does not block LC3 lipidation. Autophagy gene expression is required for efficient clearance of apoptotic cells and phagosome maturation. KIM-1-mediated phagocytosis leads to pro-tolerogenic antigen presentation, which suppresses CD4 T-cell proliferation and increases the percentage of regulatory T cells in an autophagy gene-dependent manner. Taken together, these data reveal a novel mechanism of epithelial biology linking phagocytosis, autophagy and antigen presentation to regulation of the inflammatory response. PMID:26282792

  14. Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1).

    PubMed

    Ribnicky, David M; Roopchand, Diana E; Oren, Andrew; Grace, Mary; Poulev, Alexander; Lila, Mary Ann; Havenaar, Robert; Raskin, Ilya

    2014-01-01

    The TNO intestinal model (TIM-1) of the human upper gastrointestinal tract was used to compare intestinal absorption/bioaccessibility of blueberry anthocyanins under different digestive conditions. Blueberry polyphenol-rich extract was delivered to TIM-1 in the absence or presence of a high-fat meal. HPLC analysis of seventeen anthocyanins showed that delphinidin-3-glucoside, delphinidin-3-galactoside, delphinidin-3-arabinoside and petunidin-3-arabinoside were twice as bioaccessible in fed state, whilst delphinidin-3-(6″-acetoyl)-glucoside and malvidin-3-arabinoside were twice as bioaccessible under fasted conditions, suggesting lipid-rich matrices selectively effect anthocyanin bioaccessibility. TIM-1 was fed blueberry juice (BBJ) or blueberry polyphenol-enriched defatted soybean flour (BB-DSF) containing equivalent amounts of free or DSF-sorbed anthocyanins, respectively. Anthocyanin bioaccessibility from BB-DSF (36.0±10.4) was numerically, but not significantly, greater than that from BBJ (26.3±10.3). Ileal efflux samples collected after digestion of BB-DSF contained 2.8-fold more anthocyanins than same from BBJ, suggesting that protein-rich DSF protects anthocyanins during transit through upper digestive tract for subsequent colonic delivery/metabolism.

  15. Application of Thermal Infrared Multiband Scanner (TIMS) data to mapping of Plutonic and stratified rock and assemblages in accreted terrains of the Northern Sierra, California

    NASA Technical Reports Server (NTRS)

    Taranik, James V.; Davis, David; Borengasser, Marcus

    1986-01-01

    The Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the Donner Pass area in California on September 12, 1985. The higher peaks in the area approach 9,200 feet in elevation, while the canyon of the north fork of the American River is only 3000 feet in elevation. The vegetation is dominated by conifers, although manzanita and other shrubs are present in areas where soils have developed. The data contain noise patterns which cut across scan lines diagonally. The TIMS data were analyzed using both photointerpretative and digital processing techniques. Preliminary image interpretation and field analysis confirmed that TIMS image data displays the chert units and silicic volcanics as bright red. The imagery appears to display zoning in the batholithic and hypabyssal intrusive rocks, although this was not field checked at this time. Rocks which appear to be more dioritic in composition appear purple on the imagery, while rocks more granitic in composition appear shades of red and pink. Areas that have more than 40% vegetative cover appear green on the imagery.

  16. Alternative splice variants in TIM barrel proteins from human genome correlate with the structural and evolutionary modularity of this versatile protein fold.

    PubMed

    Ochoa-Leyva, Adrián; Montero-Morán, Gabriela; Saab-Rincón, Gloria; Brieba, Luis G; Soberón, Xavier

    2013-01-01

    After the surprisingly low number of genes identified in the human genome, alternative splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes. However, it is still not known if its prevalence along the genome evolution has contributed to the overall functional protein diversity or if it simply reflects splicing noise. The (βα)8 barrel or TIM barrel is one of the most frequent, versatile, and ancient fold encountered among enzymes. Here, we analyze the structural modifications present in TIM barrel proteins from the human genome product of alternative splicing events. We found that 87% of all splicing events involved deletions; most of these events resulted in protein fragments that corresponded to the (βα)2, (βα)4, (βα)5, (βα)6, and (βα)7 subdomains of TIM barrels. Because approximately 7% of all the splicing events involved internal β-strand substitutions, we decided, based on the genomic data, to design β-strand and α-helix substitutions in a well-studied TIM barrel enzyme. The biochemical characterization of one of the chimeric variants suggests that some of the splice variants in the human genome with β-strand substitutions may be evolving novel functions via either the oligomeric state or substrate specificity. We provide results of how the splice variants represent subdomains that correlate with the independently folding and evolving structural units previously reported. This work is the first to observe a link between the structural features of the barrel and a recurrent genetic mechanism. Our results suggest that it is reasonable to expect that a sizeable fraction of splice variants found in the human genome represent structurally viable functional proteins. Our data provide additional support for the hypothesis of the origin of the TIM barrel fold through the assembly of smaller subdomains. We suggest a model of how nature explores new proteins through alternative splicing as a mechanism to diversify the

  17. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer.

    PubMed

    Heon, Elise K; Wulan, Hasi; Macdonald, Loch P; Malek, Adel O; Braunstein, Glenn H; Eaves, Connie G; Schattner, Mark D; Allen, Peter M; Alexander, Michael O; Hawkins, Cynthia A; McGovern, Dermot W; Freeman, Richard L; Amir, Eitan P; Huse, Jason D; Zaltzman, Jeffrey S; Kauff, Noah P; Meyers, Paul G; Gleason, Michelle H; Overholtzer, Michael G; Wiseman, Sam S; Streutker, Catherine D; Asa, Sylvia W; McAlindon, Timothy P; Newcomb, Polly O; Sorensen, Poul M; Press, Oliver A

    2015-08-14

    IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy.

  18. Alternative Splice Variants in TIM Barrel Proteins from Human Genome Correlate with the Structural and Evolutionary Modularity of this Versatile Protein Fold

    PubMed Central

    Ochoa-Leyva, Adrián; Montero-Morán, Gabriela; Saab-Rincón, Gloria; Brieba, Luis G.; Soberón, Xavier

    2013-01-01

    After the surprisingly low number of genes identified in the human genome, alternative splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes. However, it is still not known if its prevalence along the genome evolution has contributed to the overall functional protein diversity or if it simply reflects splicing noise. The (βα)8 barrel or TIM barrel is one of the most frequent, versatile, and ancient fold encountered among enzymes. Here, we analyze the structural modifications present in TIM barrel proteins from the human genome product of alternative splicing events. We found that 87% of all splicing events involved deletions; most of these events resulted in protein fragments that corresponded to the (βα)2, (βα)4, (βα)5, (βα)6, and (βα)7 subdomains of TIM barrels. Because approximately 7% of all the splicing events involved internal β-strand substitutions, we decided, based on the genomic data, to design β-strand and α-helix substitutions in a well-studied TIM barrel enzyme. The biochemical characterization of one of the chimeric variants suggests that some of the splice variants in the human genome with β-strand substitutions may be evolving novel functions via either the oligomeric state or substrate specificity. We provide results of how the splice variants represent subdomains that correlate with the independently folding and evolving structural units previously reported. This work is the first to observe a link between the structural features of the barrel and a recurrent genetic mechanism. Our results suggest that it is reasonable to expect that a sizeable fraction of splice variants found in the human genome represent structurally viable functional proteins. Our data provide additional support for the hypothesis of the origin of the TIM barrel fold through the assembly of smaller subdomains. We suggest a model of how nature explores new proteins through alternative splicing as a mechanism to diversify the

  19. Data Acquisition System(DAS) Sustaining Engineering

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This paper presents general information describing the Data Acquisition System contract, a summary of objectives, tasks performed and completed. The hardware deliverables which are comprised of: 1) Two ground DAS units; 2) Two flight DAS units; 3) Logistic spares; and 4) Shipping containers are described. Also included are the data requirements and scope of the contract.

  20. New Ca-Tims and La-Icp Analyses of GJ-1, Plesovice, and FC1 Reference Materials

    NASA Astrophysics Data System (ADS)

    Feldman, J. D.; Möller, A.; Walker, J. D.

    2014-12-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U-Pb zircon geochronology relies on external reference standards to monitor and correct for different mass fractionation effects and instrument drift. Common zircon reference materials used within the community, including the KU Isotope Geochemistry Laboratory, are GJ-1 (207Pb/206Pb age: 608.53 +/- 0.37Ma; Jackson et al., 2004), Plesovice (337.13 +/- 0.37 Ma; Slama et al., 2008), and FC-1 (1099.0 +/-0.6 Ma; Paces and Miller, 1993). The age distribution of zircon reference material varies slightly from sample fraction to sample fraction, and the published results for GJ-1 are slightly discordant. As a result, using the published data for the distributed standard splits can lead to small systematic variations when comparing datasets from different labs, and more high precision data are needed to evaluate potential inhomogeneity of sample splits used in different laboratories. Here we characterize these reference materials with cathodoluminescence, LA-ICP-MS traverses across grains, and high precision CA-TIMS to better constrain the ages and assess zoning of these standards, and present the data for comparison with other laboratories. Reducing systematic error by dating our own reference material lends confidence to our analyses and allows for inter-laboratory age reproducibility of unknowns. Additionally, the reduction in propagated uncertainties (especially in GJ-1, for which both the red and yellow variety will be analyzed) will be used to improve long-term reproducibility, comparisons between samples of similar age, detrital populations and composite pluton zircons. Jackson, S.E., et al., 2004, Chemical Geology, v. 211, p. 47-69. Paces, J.B. & Miller, J.D., 1993, Journal of Geophysical Research, v. 80, p. 13997-14013. Slama, J., et al., 2008, Chemical Geology, v. 249. p. 1-35.

  1. Targeting PD-1 and Tim-3 Pathways to Reverse CD8 T-Cell Exhaustion and Enhance Ex Vivo T-Cell Responses to Autologous Dendritic/Tumor Vaccines.

    PubMed

    Liu, Jingwei; Zhang, Shurong; Hu, Yuefeng; Yang, Zhaomin; Li, Jingpo; Liu, Xuesong; Deng, Lijuan; Wang, Yue; Zhang, Xiaoyan; Jiang, Ting; Lu, Xu

    2016-05-01

    The paradoxical coexistence of spontaneous tumor antigen-specific immune response with progressive disease in cancer patients need to dissect the molecular pathways involved in tumor-induced T-cell dysfunction or exhaustion. Programmed cell death 1 (PD-1) has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1-PD-L1 interactions has been shown to partially restore T-cell function. We have found that T-cell immunoglobulin mucin (Tim) 3 is expressed on CD8+ tumor-infiltrating lymphocytes (TILs) isolated from patients with colorectal cancer. All T-cell immunoglobulin mucin 3 (Tim-3+) TILs coexpress PD-1, and Tim-3+ PD-1+ CD8+ TILs represent the predominant fraction of Tcells infiltrating tumors. Tim-3+PD-1+ CD8+ TILs exhibit the most severe exhausted phenotype as defined by failure to produce cytokines, such as interferon-γ, tumor necrosis factor-α, and interleukin-2. We further find that combined targeting of the Tim-3 and PD-1 pathways increased the frequencies of not only interferon-γ and tumor necrosis factor-α but also frequencies of proliferating tumor antigen-specific CD8+ T cells than targeting either pathway alone. A concomitant decrease in regulatory T cells and enhanced killing in a cytotoxicity assay was observed. Collectively, our findings support the use of Tim-3-Tim-3L blockade together with PD-1-PD-L1 blockade to reverse tumor-induced T-cell exhaustion/dysfunction in patients with colorectal cancer.

  2. High-Resolution Zircon U-Pb CA-TIMS Dating of the Carboniferous—Permian Successions, Paraná Basin, Brazil

    NASA Astrophysics Data System (ADS)

    Griffis, N. P.; Mundil, R.; Montanez, I. P.; Isbell, J.; Fedorchuk, N.; Lopes, R.; Vesely, F.; Iannuzzi, R.

    2015-12-01

    The late Paleozoic Ice Age (LPIA) is Earth's only record of a CO2-forced climatic transition from an icehouse to greenhouse state in a vegetated world. Despite a refined framework of Gondwanan ice distribution, questions remain about the timing, volume, and synchronicity of high-latitude continental ice and the subsequent deglaciation. These questions ultimately preclude our understanding of linkages between ice volume, sea level, and high- and low-latitude climate. Poor constraints on the timing and synchronicity of glacial and interglacial transitions reflect a lack of high-resolution radioisotopic dates from high-latitude, ice-proximal Carboniferous-Permian successions. The Rio Bonito Fm in Rio Grande do Sul State of southern Brazil hosts the oldest non-glaciogenic Carboniferous- Permian deposits of the Paraná Basin, thus recording the icehouse-to-greenhouse transition. Despite a widespread effort over the last two decades to constrain these deposits in time by means of U-Pb zircon geochronology, published data sets of the Candiota and Faxinal coals of the Rio Bonito Fm host discrepancies that may reflect post- eruptive open system behavior of zircon and analytical artifacts. These discrepancies have hindered the correlation of the Candiota and Faxinal sediments within the larger Gondwanan framework. Here we present the first U-Pb ages on closed system single zircons using CA-TIMS techniques on Permo-Carboniferous ash deposits of the Paraná Basin. Preliminary results indicate two major and distinct coal-forming periods that are separated by ca 10 Ma. Our results and conclusions are not in agreement with multi- crystal U-Pb TIMS and SIMS ages that suggest coeval deposition of the Candiota and Faxinal coals. CA-TIMS analyses applied to zircons from additional ash deposits are aimed at constructing a robust chronostratigraphic framework for the Carboniferous- Permian succession of the Paraná Basin, which will facilitate a better understanding of the timing and

  3. Overexpression of Tim-3 reduces Helicobacter pylori-associated inflammation through TLR4/NFκB signaling in vitro.

    PubMed

    Wang, Fucai; Mao, Zhirong; Liu, Dongsheng; Yu, Jing; Wang, Youhua; Ye, Wen; Lin, Dongjia; Zhou, Nanjin; Xie, Yong

    2017-03-21

    The present study aimed to investigate the interaction between T-cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF‑κB) signaling in Helicobacter pylori-infected RAW264.7 macrophage cells. RAW264.7 cells were co‑cultured with H. pylori SS1 at different bacteria/cell ratios, and subsequently the mRNA expression of Tim‑3, TLR4, and myeloid differentiation factor 88 (MyD88) was measured by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR). Furthermore, the effect of Tim‑3 overexpression was examined by transfection of RAW264.7 with pLVX-IRES-ZsGreen-Tim-3 and co‑culturing with H. pylori. mRNA and protein expression levels were then analyzed for Tim‑3, TLR4, MyD88, and phosphorylated (p‑) NF‑κB by RT‑qPCR and western blot analysis respectively. The concentrations of pro‑inflammatory cytokines [tumor necrosis factor‑α (TNF‑α), interleukin 6 (IL-6), interferon‑γ (IFN‑γ) and interleukin 10 (IL‑10)] released in the culture supernatants were measured by ELISA. H. pylori stimulation resulted in a significant increase of Tim‑3, TLR4, and MyD88 mRNA expression in RAW264.7 cells. H. pylori stimulation upregulated Tim‑3 expression even in the Tim‑3‑overexpressing RAW264.7 cells compared with unstimulated cells. TLR4, MyD88, and pNF‑κB protein expression and pro‑inflammatory cytokines (TNF‑α, IL‑6, and IFN‑γ) release levels were increased in the control RAW264.7 cells following H. pylori infection, but not in the Tim-3-overexpressing RAW264.7 cells. By contrast, IL‑10 levels were decreased following H. pylori infection in both control and Tim‑3‑overexpressing RAW264.7 cells. Overexpression of Tim-3 reduced H. pylori-associated inflammation in RAW264.7 macrophages, by downregulating expression of proteins in the TLR4 pathway and release of pro‑inflammatory cytokines. These findings suggest that Tim‑3 serves a crucial role

  4. Characterization Activities to Evaluate Chlorinated Solvent Discharges to Tims Branch from the A/M Area of the Savannah River Site

    SciTech Connect

    Jackson, D.G.

    2001-02-23

    The objective of this investigation was to identify those regions of plume outcrop along Tims Branch southeast of A/M Area and to establish fixed monitoring points along the seepline to evaluate proposed remediation needs and to support long-term monitoring activities in the vicinity of the seepline. The characterization approach employed in completing these tasks was dynamic and graded. Three stages of characterization were used to evaluate the outcrop region, with the results from each of the previous activities used to direct subsequent characterization.

  5. Uncle Tim's Dilemma

    ERIC Educational Resources Information Center

    DiBiase, Warren

    2009-01-01

    In this investigation, students make predictions and observations of a counterintuitive phenomenon. Given the scenario of a boat filled with a set of large rocks placed in a swimming pool, the students investigate what happens to both the water level in the pool and the level at which the boat floats when the rocks are taken out of the boat and…

  6. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable

    PubMed Central

    Fleischmann, Roy M; van der Heijde, Désirée; Gardiner, Philip V; Szumski, Annette; Marshall, Lisa; Bananis, Eustratios

    2017-01-01

    Background In most patients with rheumatoid arthritis (RA), Disease Activity Score 28-joint count C reactive protein (DAS28-CRP) is lower than DAS28 erythrocyte sedimentation rate (DAS28-ESR), suggesting that use of the DAS28-ESR cut-off to assess high disease activity (HDA) with DAS28-CRP may underestimate the number of patients with HDA. We determined the DAS28-CRP value corresponding to the validated DAS28-ESR cut-off for HDA. Methods Baseline data were pooled from 2 clinical studies evaluating etanercept (ETN) plus methotrexate (MTX) or MTX in early RA; DAS28-CRP and DAS28-ESR were obtained, allowing the determination of the DAS28-CRP HDA value best corresponding to the DAS28-ESR cut-off of >5.1. Results At baseline, as expected, fewer patients had HDA by DAS28-CRP than DAS28-ESR; DAS28-CRP>5.1 and DAS28-ESR>5.1 had only modest agreement (κ coefficients 0.45–0.54). Mean DAS28-CRP and DAS28-ESR were 5.7 and 6.2, respectively, in the ETN+MTX group (n=571), and 6.0 and 6.5 in the MTX group (n=262). A DAS28-CRP cut-off of 4.6 corresponded to a DAS28-ESR cut-off of 5.1. Conclusions We have shown that a DAS28-CRP of 4.6 corresponds to 5.1 for DAS28-ESR. Since this is substantially lower than the DAS28-ESR cut-off of 5.1, using 5.1 as the cut-off for DAS28-CRP underestimates disease activity in RA. Trial registration number NCT00195494; NCT00913458. PMID:28255449

  7. Enhanced Virus-Specific CD8+ T Cell Responses by Listeria monocytogenes-Infected Dendritic Cells in the Context of Tim-3 Blockade

    PubMed Central

    Ma, Cheng J.; Ren, Jun P.; Li, Guang Y.; Wu, Xiao Y.; Brockstedt, Dirk G.; Lauer, Peter; Moorman, Jonathan P.; Yao, Zhi Q.

    2014-01-01

    In this study, we engineered Listeria monocytogens (Lm) by deleting the LmΔactA/ΔinlB virulence determinants and inserting HCV-NS5B consensus antigens to develop a therapeutic vaccine against hepatitis C virus (HCV) infection. We tested this recombinant Lm-HCV vaccine in triggering of innate and adaptive immune responses in vitro using immune cells from HCV-infected and uninfected individuals. This live-attenuated Lm-HCV vaccine could naturally infect human dendritic cells (DC), thereby driving DC maturation and antigen presentation, producing Th1 cytokines, and triggering CTL responses in uninfected individuals. However, vaccine responses were diminished when using DC and T cells derived from chronically HCV-infected individuals, who express higher levels of inhibitory molecule Tim-3 on immune cells. Notably, blocking Tim-3 signaling significantly improved the innate and adaptive immune responses in chronically HCV-infected patients, indicating that novel strategies to enhance the potential of antigen presentation and cellular responses are essential for developing an effective therapeutic vaccine against HCV infection. PMID:24498204

  8. Enhanced virus-specific CD8+ T cell responses by Listeria monocytogenes-infected dendritic cells in the context of Tim-3 blockade.

    PubMed

    Ma, Cheng J; Ren, Jun P; Li, Guang Y; Wu, Xiao Y; Brockstedt, Dirk G; Lauer, Peter; Moorman, Jonathan P; Yao, Zhi Q

    2014-01-01

    In this study, we engineered Listeria monocytogens (Lm) by deleting the LmΔactA/ΔinlB virulence determinants and inserting HCV-NS5B consensus antigens to develop a therapeutic vaccine against hepatitis C virus (HCV) infection. We tested this recombinant Lm-HCV vaccine in triggering of innate and adaptive immune responses in vitro using immune cells from HCV-infected and uninfected individuals. This live-attenuated Lm-HCV vaccine could naturally infect human dendritic cells (DC), thereby driving DC maturation and antigen presentation, producing Th1 cytokines, and triggering CTL responses in uninfected individuals. However, vaccine responses were diminished when using DC and T cells derived from chronically HCV-infected individuals, who express higher levels of inhibitory molecule Tim-3 on immune cells. Notably, blocking Tim-3 signaling significantly improved the innate and adaptive immune responses in chronically HCV-infected patients, indicating that novel strategies to enhance the potential of antigen presentation and cellular responses are essential for developing an effective therapeutic vaccine against HCV infection.

  9. Long-Term Performance of Pb Isotopic Analysis by TIMS with 202Pb-205Pb Double Spike

    NASA Astrophysics Data System (ADS)

    Amelin, Y.; Connelly, J. N.

    2008-05-01

    The 202Pb-205Pb-233U-235U spike (Pb DS), prepared at the Geological Survey of Canada in 2005 [1], and the 202Pb-205Pb-235U spike, prepared at the Department of Geosciences, University of Oslo [2], have been used for more than two years. Both spikes are routinely used for TIMS analysis of Pb with internal fractionation correction for U-Pb dating of various rocks and minerals, including dating perovskite [2] and meteorites and their components [1, 4-7]. A few hundred standard and sample Pb DS analyses were acquired with these two spikes using Triton TI mass spectrometers at the Geological Survey of Canada, US Geological Survey and the Australian National University, a Finnigan-MAT 261 mass spectrometer at The University of Texas at Austin and a Finnigan-MAT 262 mass spectrometer at the University of Oslo. All analyses were performed using high efficiency silicic acid emitter [8] and a static multicollector mode if the samples were sufficiently large to produce an ion beam greater than ca. 2-5×10-14 A on 206Pb and 207Pb. These data allow us to evaluate long - term performance of the Pb DS procedure for sub-nanogram samples of Pb. The performance of this procedure is evaluated on the basis of the long-term reproducibility of analyses of isotopic standards, and from improving quality of linear fits in Pb-Pb isochron diagrams (and, hence, improved precision of ages) compared to the same data reduced using external normalization. The data for 0.3 ng loads of SRM-981, analyzed with the batches of samples in 2006 and 2007 at the GSC, yield the mean 204Pb/206Pb of 0.05904±0.00013 (0.226% 2σ), #207Pb/206Pb of 0.91483±0.00018 (0.020% 2σ)), and 208Pb/206Pb of 2.16771±0.00054 (0.025% 2σ)). These values and errors are similar to those reported in [1] for the loads of the same size, and to the values obtained for similar loads at the USGS and at ANU over shorter periods of time. The precision and reproducibility of sample analysis and standard analyses is similar, and

  10. Dasty3, a WEB framework for DAS

    PubMed Central

    Villaveces, Jose M.; Jimenez, Rafael C.; Garcia, Leyla J.; Salazar, Gustavo A.; Gel, Bernat; Mulder, Nicola; Martin, Maria; Garcia, Alexander; Hermjakob, Henning

    2011-01-01

    Motivation: Dasty3 is a highly interactive and extensible Web-based framework. It provides a rich Application Programming Interface upon which it is possible to develop specialized clients capable of retrieving information from DAS sources as well as from data providers not using the DAS protocol. Dasty3 provides significant improvements on previous Web-based frameworks and is implemented using the 1.6 DAS specification. Availability: Dasty3 is an open-source tool freely available at http://www.ebi.ac.uk/dasty/ under the terms of the GNU General public license. Source and documentation can be found at http://code.google.com/p/dasty/. Contact: hhe@ebi.ac.uk PMID:21798964

  11. Physik gestern und heute Das Eiskalorimeter

    NASA Astrophysics Data System (ADS)

    Heering, P.

    2003-07-01

    Kalorimetrische Messungen gehören heute zum experimentellen Standardrepertoire im Bereich der Thermodynamik und der physikalischen Chemie. Das erste Gerät für derartige Messungen entwickelten Ende des 18. Jahrhunderts die französischen Wissenschaftler Antoine Laurent Lavoisier und Pierre Simon de Laplace.

  12. GHRSST-14 DAS-TAG Report

    NASA Technical Reports Server (NTRS)

    Armstrong, Edward; Piolle, Jean Francois

    2013-01-01

    The DAS-TAG provides the informatics and data management expertise in emerging information technologies for the GHRSST community. It provides expertise in data and metadata formats and standards, fosters improvements for GHRSST data curation, experiments with new data processing paradigms, and evaluates services and tools for data usage. It provides a forum for producer and distributor data management issues and coordination.

  13. Application of U-Pb ID-TIMS dating to the end-Triassic global crisis: testing the limits on precision and accuracy in a multidisciplinary whodunnit (Invited)

    NASA Astrophysics Data System (ADS)

    Schoene, B.; Schaltegger, U.; Guex, J.; Bartolini, A.

    2010-12-01

    The ca. 201.4 Ma Triassic-Jurassic boundary is characterized by one of the most devastating mass-extinctions in Earth history, subsequent biologic radiation, rapid carbon cycle disturbances and enormous flood basalt volcanism (Central Atlantic Magmatic Province - CAMP). Considerable uncertainty remains regarding the temporal and causal relationship between these events though this link is important for understanding global environmental change under extreme stresses. We present ID-TIMS U-Pb zircon geochronology on volcanic ash beds from two marine sections that span the Triassic-Jurassic boundary and from the CAMP in North America. To compare the timing of the extinction with the onset of the CAMP, we assess the precision and accuracy of ID-TIMS U-Pb zircon geochronology by exploring random and systematic uncertainties, reproducibility, open-system behavior, and pre-eruptive crystallization of zircon. We find that U-Pb ID-TIMS dates on single zircons can be internally and externally reproducible at 0.05% of the age, consistent with recent experiments coordinated through the EARTHTIME network. Increased precision combined with methods alleviating Pb-loss in zircon reveals that these ash beds contain zircon that crystallized between 10^5 and 10^6 years prior to eruption. Mineral dates older than eruption ages are prone to affect all geochronologic methods and therefore new tools exploring this form of “geologic uncertainty” will lead to better time constraints for ash bed deposition. In an effort to understand zircon dates within the framework of a magmatic system, we analyzed zircon trace elements by solution ICPMS for the same volume of zircon dated by ID-TIMS. In one example we argue that zircon trace element patterns as a function of time result from a mix of xeno-, ante-, and autocrystic zircons in the ash bed, and approximate eruption age with the youngest zircon date. In a contrasting example from a suite of Cretaceous andesites, zircon trace elements

  14. Chlorine Isotopes: As a Possible Tracer of Fluid/Bio-Activities on Mars and a Progress Report on Chlorine Isotope Analysis by TIMs

    NASA Technical Reports Server (NTRS)

    Nakamura, N.; Nyquist, L.E.; Reese, Y.; Shih, C-Y.; Numata, M.; Fujitani, T.; Okano, O.

    2009-01-01

    Significantly large mass fractionations between chlorine isotopes (Cl-35, Cl-37) have been reported for terrestrial materials including both geological samples and laboratory materials. Also, the chlorine isotopic composition can be used as a tracer for early solar system processes. Moreover, chlorine is ubiquitous on the Martian surface. Typical chlorine abundances in Gusev soils are approx.0.5 %. The global surface average chlorine abundance also is approx.0.5 %. Striking variations among outcrop rocks at Meridiani were reported with some chlorine abundances as high as approx.2%. Characterizing conditions under which chlorine isotopic fractionation may occur is clearly of interest to planetary science. Thus, we have initiated development of a chlorine isotopic analysis technique using TIMS at NASA-JSC. We present here a progress report on the current status of development at JSC and discuss the possible application of chlorine isotopic analysis to Martian meteorites in a search for fluid- and possibly biological activity on Mars.

  15. Radiogenic Isotopes As Paleoceanographic Tracers in Deep-Sea Corals: Advances in TIMS Measurements of Pb Isotopes and Application to Southern Ocean Corals

    NASA Astrophysics Data System (ADS)

    Wilson, D. J.; van de Flierdt, T.; Bridgestock, L. J.; Paul, M.; Rehkamper, M.; Robinson, L. F.; Adkins, J. F.

    2014-12-01

    Deep-sea corals have emerged as a valuable archive of deep ocean paleoceanographic change, with uranium-series dating providing absolute ages and the potential for centennial resolution. In combination with measurements of radiocarbon, neodymium isotopes and clumped isotopes, this archive has recently been exploited to reconstruct changes in ventilation, water mass sourcing and temperature in relation to millennial climate change. Lead (Pb) isotopes in both corals and seawater have also been used to track anthropogenic inputs through space and time and to trace transport pathways within the oceans. Better understanding of the oceanic Pb cycle is emerging from the GEOTRACES programme. However, while Pb isotopes have been widely used in environmental studies, their full potential as a (pre-anthropogenic) paleoceanographic tracer remains to be exploited. In deep-sea corals, challenges exist from low Pb concentrations in aragonite in comparison to secondary coatings, the potential for contamination, and the efficient elemental separation required for measurement by thermal ionisation mass spectrometry (TIMS). Here we discuss progress in measuring Pb isotopes in coral aragonite using a 207Pb-204Pb double spike on a ThermoFinnigan Triton TIMS. For a 2 ng NIST-981 Pb standard, the long term reproducibility (using 1011 Ω resistors) is ~1000 ppm (2 s.d.) on 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios. We now show that using a new 1012 Ω resistor to measure the small 204Pb beam improves the internal precision on these ratios from ~500 ppm (2 s.e.) to ~250 ppm (2 s.e.) and we envisage a potential improvement in the long term reproducibility as a consequence. We further assess the internal precision and external reproducibility of our method using a BCR-2 rock standard and an in-house coral standard. Preliminary evidence on the application of this method to natural samples is derived from cleaning experiments and replication tests on deep-sea corals from the Southern

  16. Advances in ID-TIMS and LA-MC-ICP-MS U-Pb mass spectrometry with applications to geochronology and environmental U analysis

    NASA Astrophysics Data System (ADS)

    Parrish, R. R.; Noble, S. R.; Condon, D. J.; Horstwood, M. S.; Bowring, S.; Schoene, B.; Crowley, Q.

    2006-12-01

    Recent advances highlighted are the analysis of tiny quantities of U and Pb isotopes, ID-TIMS U-Pb dating using EARTHTIME double spike tracers and improved detectors, and the performance of integrated LA-MC- ICP-MS systems for U-Pb dating. Detector improvements: The use of 1012 ohm resistors with faraday detectors has shown that their noise levels conform closely to prediction and overlap ion intensities previously in the realm of ion counting detectors, enabling multiple faraday ion detection for <20 pg of radiogenic Pb. A trade-off in slower response time, however, hinders rapid peak-switching data acquisition and favours use in static multicollection mode. Sub-ng high precision U analysis of complex matrices: The accurate measurement of U isotopes, including ^{236}U at the <1e^{-5} level, in sub-ng quantities of uranium, represents a very significant challenge to the detection of human internal uranium contamination many years after exposure. We have used MC-ICP-MS instruments with mixed SEM-faraday detectors along with improvements in chemical separation and purification to measure uranium isotopes in urine with detection limits of a few fg. In a large study >95% of samples intentionally blind-doped with very small amounts (~3 fg to 40 pg) of either depleted uranium or pure ^{236}U were accurately quantified from a sample cohort of more than 300 urine samples. ID-TIMS: Recent developments spearheaded by the EARTHTIME project (www.earth-time.org) has driven a community effort to improve inter-laboratory U-Pb comparability (and accuracy) via the development of mixed U-Pb tracer solutions for community use. In addition a ^{202}Pb-^{205}Pb-^{233}U-^{235}U double spike has been mixed as part of this project aimed at achieving increased precision via real time Pb mass bias determination. LA-MC-ICP-MS: The Pb/U and 207Pb/206Pb precision by LA-(MC)-ICP-MS can be comparable to SIMS U-Pb dating of zircon. A weakness of LA-ICP-MS U-Pb analysis has been the large

  17. Comparing pre- and post-chemical abrasion ages for Miocene Peach Springs Tuff zircon from ID-TIMS and SIMS analyses

    NASA Astrophysics Data System (ADS)

    Lidzbarski, M. I.; Mundil, R.; Miller, J. S.; Vazquez, J. A.

    2012-12-01

    removes micro-inclusions that typically contain common Pb. Thermal annealing followed by CA techniques were used for ID-TIMS dating of a sub-set of zircon crystals previously analyzed by SIMS. Prior to TIMS analyses, zircon crystals were imaged by scanning electron microscopy (SEM) to evaluate the effects of CA on crystal domains sampled by SIMS. SEM images reveal that whole portions of crystals were removed by the CA technique, and a heterogeneous pattern of etching that was not confined to specific compositional zones visible in cathodoluminescence. Most of the SIMS sputter pits that yield spurious ages, are associated with etching and/or preferential annealing by the combined annealing and CA technique, suggesting that the young ages relative to the 40Ar/39Ar age may be due to Pb loss. ID-TIMS yields a coherent U-Pb age population of 18.8 Ma, with several older and younger crystals that might reflect xenocrysts, Pb-loss, and/or younger crystallization. In order to maintain spatial resolution and further evaluate the effects of Pb-loss in PST zircon, the annealing and CA-technique will be applied to zircon prior to SIMS dating. References: Reid and Coath, 2000, Geology 28: 443 Renne et al., 2010, GCA 78: 5349

  18. Permian U-Pb (CA-TIMS) zircon ages from Australia and China: Constraining the time scale of environmental and biotic change

    NASA Astrophysics Data System (ADS)

    Denyszyn, S. W.; Mundil, R.; Metcalfe, I.; He, B.

    2010-12-01

    In eastern Australia, the interconnected Bowen and Sydney Basins are filled with terrestrial sediments of late Paleozoic to early Mesozoic age. These sedimentary units record significant evolutionary events of eastern Gondwana during the time interval between two major mass extinctions (end Middle Permian and Permian-Triassic), and also provide lithological evidence for the Carboniferous-Permian Late Paleozoic Ice Age of southern Pangea, considered to be divisible into up to seven discrete glaciation events in Australia [e.g., 1]. These glaciations are currently assigned ages that indicate that the last of the glaciations predate the end Middle Permian mass extinction at ca. 260 Ma. However, the estimates for the time and durations are largely based on biostratigraphy and lithostratigraphy that, in the absence of robust and precise radioisotopic ages, are unacceptably fragile for providing an accurate high-resolution framework. Interbedded with the sediments are numerous tuff layers that contain zircon, many of which are associated with extensive coal measures in the Sydney and Bowen Basins. Published SHRIMP U-Pb zircon ages [2, 3] have been shown to be less precise and inaccurate when compared to ages applying the CA-TIMS method to the same horizons. Also within the late Middle Permian, the eruption of the Emeishan flood basalts in SW China has been proposed to have caused the end Middle Permian mass extinction [e.g., 4], though a causal link between these events demands a rigorous test that can only be provided by high-resolution geochronology. We present new U-Pb (CA-TIMS) zircon ages on tuff layers from the Sydney and Bowen Basins, with the purpose of generating a timescale for the Upper Permian of Australia to allow correlation with different parts of the world. Initial results, with permil precision, date a tuff layer within the uppermost Bandanna Fm. to ca. 252 Ma, a tuff within the Moranbah Coal Measures to ca. 256 Ma, and a tuff within the Ingelara Fm. to

  19. Amplifying Earth history: Zircon U-Pb geochronology by ID-TIMS at the 0.1 ‰ level using new 1013 ohm resistors

    NASA Astrophysics Data System (ADS)

    Wotzlaw, Jörn-Frederik; von Quadt, Albrecht

    2016-04-01

    Precise and accurate radiometric dating of volcanic ash beds in sedimentary successions is the backbone of the numerical calibration of Earth history. Uranium-lead geochronology by isotope dilution thermal ionization mass spectrometry (ID-TIMS) is the most precise and accurate dating technique and is applicable to most of Earth history from the Hadean to the Pleistocene. The accessory mineral zircon is the prime target material due to its commonly high U concentration, virtually no initial Pb and high daughter-product retentivity. However, complex crystallization histories as well as magmatic and sedimentary recycling of zircons require the analysis of single crystals resulting in small amounts of radiogenic Pb (Pb* usually <100 pg) available for mass spectrometry. Precise and accurate isotope ratio determinations on such small samples require highly sensitive ion detection systems making ion counting detectors such as secondary electron multipliers and Daly photomultipliers the most commonly employed detectors for the analysis of small Pb* ion beams. While these detector systems are highly sensitive they are limited by their restricted linear dynamic range and require dynamic peak hopping to collect multiple isotopes. We recently demonstrated the applicability of new 1013 ohm resistors in the Faraday cup amplifier feedback loop for the static multi-collection of all tracer and sample Pb isotopes with 202,205,206,207,208Pb measured on Faraday cups and 204Pb measured in the axial SEM of a Thermo Scientific TRITON Plus TIMS instrument [1]. These measurements take advantage of the superior stability of Faraday detectors, their significantly larger dynamic range and the multiple advantages of static multi collector analyses (longer counting on peak, simultaneous collection of all isotopes etc.). Here, we document recent advances in our analytical protocols that further improve the precision, accuracy and reproducibility of U and Pb isotope ratio measurements of small

  20. An Improved Method for TIMS High Precision Nd Isotopic Analysis of Very Small Aliquots (1- 10ng) With Example Application in Garnet Sm/Nd Geochronology

    NASA Astrophysics Data System (ADS)

    Baxter, E. F.; Harvey, J.; Mehl, L. Y.; Peterman, E. M.

    2007-12-01

    Technological and scientific developments have demonstrated both the attainability and the utility of very high precision (i.e. 5-20ppm 2 σ) Nd isotopic measurements with TIMS. However such high precision has been limited to relatively large aliquots of Nd, on the order of several hundred nanograms. Several potential applications of precise Nd isotopic measurements, including garnet Sm/Nd geochronology, do not always permit such large samples, instead yielding only a few nanograms of Nd. We have explored and tested an improved method for Nd isotopic analysis of such small (1-10ng) aliquots of Nd using the NdO+ method with a Triton TIMS at Boston University. Analyzing Nd isotopes as the oxide is a well known technique, frequently involving an oxygen bleed valve. Instead, we forego the bleed valve and load samples with a TaO slurry which provides the oxygen source. Using an in-house Nd isotopic standard solution, 4ng loads easily yield stable 2.0-2.5 volt beams resulting in internal precisions of 10ppm 2 σ RSE. Within barrel external precision of 4ng loads of the Nd standard is 13ppm 2 σ RSD (n=20). Long term (6 months, six analysts) external precision of 4ng loads of the standard is currently 23ppm 2 σ RSD (n=55) suggesting that further improvements are possible. As a further test of this method, we dissolved a natural rock sample (a metapelite), separated the Nd using TRU- spec and MLA column chemistry, and loaded nineteen 4ng loads in one barrel. Within barrel external precision was 21ppm 2 σ RSD (n=18). This precision represents a significant advance over previous NdO+ analyses of small samples using an oxygen bleed valve. The TaO loading method for small Nd aliquots is useful in Sm/Nd garnet geochronology as exemplified by two case studies. Garnets from eclogite facies gneisses from Norway ran very well with 2.4-18ng loads and yielded age precision as good as 0.8 million years 2 σ. Conversely, garnets from blueschist facies rocks from Sifnos, Greece, ran

  1. PoroTomo Project - Subatask 6.2: Deploy and Operate DAS and DTS arrays - DAS Earthquake Data

    SciTech Connect

    Kurt Feigl

    2016-03-21

    The submitted data correspond to the vibration caused by a 3.4 M earthquake and captured by the DAS horizontal and vertical arrays during the PoroTomo Experiment. Earthquake information : M 4.3 - 23km ESE of Hawthorne, Nevada Time: 2016-03-21 07:37:10 (UTC) Location: 38.479°N 118.366°W Depth: 9.9 km Files for horizontal DAS array (each file is 30 s long and contain 8700 channels): PoroTomo_iDAS16043_160321073721.sgy PoroTomo_iDAS16043_160321073751.sgy Files for vertical DAS Array (each file is 30 s long and contain 380 channels): PoroTomo_iDAS025_160321073717.sgy PoroTomo_iDAS025_160321073747.sgy

  2. Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation.

    PubMed

    Niwa, Haruna; Satoh, Takahiro; Matsushima, Yuki; Hosoya, Kazuki; Saeki, Kazumi; Niki, Toshiro; Hirashima, Mitsuomi; Yokozeki, Hiroo

    2009-08-01

    Tim-3 is a cell surface molecule preferentially expressed in Th1 and Th17 cells. Galectin-9 is a ligand for Tim-3 and the binding of galectin-9 to Tim-3 induces apoptosis. We recently developed a stable form of galectin-9 (sGal-9) by partial deletion of the linker peptide. In this study, we characterized the therapeutic effects of sGal-9 on inflammatory reactions in contact hypersensitivity and IL-23-induced psoriatic mouse models. In contact hypersensitivity in mice, the ear swelling response was suppressed by sGal-9. In vitro treatment with sGal-9 resulted in cell apoptosis of CD4, CD8, and hepatic NK cells. sGal-9-treated mice had decreased IFN-gamma- and IL-17-producing T cells. Similarly, sGal-9 reduced epidermal thickness and dermal cellular infiltrate levels in IL-23-induced psoriasis-like skin inflammation. This was accompanied by decreased skin lesion levels of IL-17 and IL-22. sGal-9 may be a unique and useful therapeutic tool for the treatment of Th1- and/or Th17-mediated skin inflammation.

  3. Partial melting and rapid exhumation of a Pliocene UHP terrane: CA-TIMS zircon results from Normanby Island, Papau New Guinea

    NASA Astrophysics Data System (ADS)

    DesOrmeau, J. W.; Gordon, S. M.; Little, T. A.; Bowring, S. A.

    2012-12-01

    Some ultra-high pressure (UHP) terranes contain eclogite embedded within migmatitic gneisses that preserve evidence for multiple episodes of partial melting. Understanding the mechanisms by which crustal rocks are subducted to mantle depths and subsequently exhumed requires understanding the timing of metamorphism and the timing and role of partial melting. The D'Entrecasteaux Islands of southeastern Papua New Guinea (PNG) expose Pliocene UHP eclogites contained within migmatitic host gneisses. Garnet-whole rock Lu-Hf geochronology suggests UHP metamorphism may have begun by ca. 7 Ma, and Ar-Ar thermochronology indicates that the rocks were exhumed to the surface by ca. 2 Ma; the history between 7 and 2 Ma is crucial for tectonic models of PNG. We have applied U-Pb chemical-abrasion thermal-ionization mass spectrometry (CA-TIMS) geochronology to zircons separated from granitoid intrusions within the host gneisses to better understand the timing and role of melting in the exhumation of the PNG UHP rocks. Three granodiorite intrusions were collected from Normanby Island as it has received far less study in previous investigations than the other D'Entrecasteaux Islands (Goodenough and Fergusson) and exposes the contact of the UHP-HP rocks against the structurally overlying, weakly metamorphosed rocks of the Papuan ultramafic belt (PUB). From the west side of Normanby dome in contact with the PUB, zircons from a foliated protomylonitic granodiorite sill yielded 206Pb/238U dates of ca. 4.1 Ma. In comparison, on the eastern side of Normanby dome, zircons from a weakly foliated, discordant pegmatitic dike yielded a complex array of zircon analyses and the youngest dates are ca. 4.1 Ma. The zircons extracted from these deformed intrusions are interpreted to date melt emplacement, crystallization, and zircon growth, which may be coeval with amphibolite facies (570-730 °C and ~7-12 Kbar) metamorphism recorded from Goodenough and Fergusson Islands. Zircons from a non

  4. U-Pb geochronology of zircon and polygenetic titanite from the Glastonbury Complex, Connecticut, USA: An integrated SEM, EMPA, TIMS, and SHRIMP study

    USGS Publications Warehouse

    Aleinikoff, J.N.; Wintsch, R.P.; Fanning, C.M.; Dorais, M.J.

    2002-01-01

    U-Pb ages for zircon and titanite from a granodioritic gneiss in the Glastonbury Complex, Connecticut, have been determined using both isotope dilution thermal ionization mass spectrometry (TIMS) and the sensitive high resolution ion microprobe (SHRIMP). Zircons occur in three morphologic populations: (1) equant to stubby, multifaceted, colorless, (2) prismatic, dark brown, with numerous cracks, and (3) elongate, prismatic, light tan to colorless. Cathodoluminescence (CL) imaging of the three populations shows simple concentric oscillatory zoning. The zircon TIMS age [weighted average of 207Pb/206Pb ages from Group 3 grains-450.5 ?? 1.6 Ma (MSWD=1.11)] and SHRIMP age [composite of 206Pb/238 U age data from all three groups-448.2 ?? 2.7 Ma (MSWD = 1.3)], are interpreted to suggest a relatively simple crystallization history. Titanite from the granodioritic gneiss occurs as both brown and colorless varieties. Scanning electron microscope backscatter (BSE) images of brown grains show multiple cross-cutting oscillatory zones of variable brightness and dark overgrowths. Colorless grains are unzoned or contain subtle wispy or very faint oscillatory zoning. Electron microprobe analysis (EMPA) clearly distinguishes the two populations. Brown grains contain relatively high concentrations of Fe2O3, Ce2O3 (up to ~ 1.5 wt.%), Nb2O5, and Zr. Cerium concentration is positively correlated with total REE + Y concentration, which together can exceed 3.5 wt.%. Oscillatory zoning in brown titanite is correlated with variations in REE concentrations. In contrast, colorless titanite (both as discrete grains and overgrowths on brown titanite) contains lower concentrations of Y, REE, Fe2O3, and Zr, but somewhat higher Al2O3 and Nb2O5. Uranium concentrations and Th/U discriminate between brown grains (typically 200-400 ppm U; all analyses but one have Th/U between about 0.8 and 2) and colorless grains (10-60 ppm U; Th/U of 0-0.17). In contrast to the zircon U-Pb age results, SHRIMP U

  5. High-precision TIMS U-Pb dating and SHRIMP trace element analyses of zircons from plutonic crust from ODP Hole 735B, Atlantis Bank, Southwest Indian Ridge

    NASA Astrophysics Data System (ADS)

    Rioux, M. E.; Cheadle, M. J.; John, B. E.; Bowring, S. A.; Wooden, J. L.; Baines, G.

    2012-12-01

    Ocean Drilling Program Hole 735B at Atlantis Bank on the Southwest Indian Ridge is the deepest drill hole (1508m) into plutonic oceanic crust. The recovered core provides the opportunity to study both the processes and timescales of lower crustal accretion at a slow-spreading mid-ocean ridge. Major element chemistry suggests that the crust is made up of three 200-1000m thick igneous series (Natland and Dick, 2002). Previous SHRIMP U/Pb dating of zircons from oxide gabbro and felsic/dioritic dikes/veins from the length of the core found no resolvable age differences, suggesting rapid crustal growth; SHRIMP Th-corrected weighted mean 206Pb/238U dates ranged from 11.86 ± 0.20 to 12.13 ± 0.21 Ma (Baines et al., 2009). Here we report combined SHRIMP chemical analyses and high precision TIMS U-Pb geochronology on zircons from a suite of fifteen samples from depths of 26-1430 mbsf. The samples are from each of the three main intrusive series and range from oxide gabbro to diorite and granodiorite dikes/veins. Single grain TIMS 206Pb/238U date uncertainties for most analyses range from ~0.01-0.2 Ma and weighted mean 206Pb/238U date uncertainties range from ~0.004-0.07 Ma, providing precise constraints on the timing and duration of magmatism. Zircon chemistry is variable between samples (John et al., this meeting). Ti and Hf from spot analyses within individual samples range from tight clusters of data to linear trends of decreasing Ti with increasing Hf. Apparent Ti-in-zircon temperature variations within samples range from ~60-230°C, and variations within single grains are as large as 160°C. For zircons with significant chemical zoning, the cores are typically higher in Ti and lower in Hf than the rims. Th-corrected single grain 206Pb/238U dates from individual samples typically overlap within uncertainty, consistent with crystallization of a single batch of magma with no evidence for assimilation of older crust or protracted crystallization, as has been seen in high

  6. U.S. Tsunami Information technology (TIM) Modernization:Developing a Maintainable and Extensible Open Source Earthquake and Tsunami Warning System

    NASA Astrophysics Data System (ADS)

    Hellman, S. B.; Lisowski, S.; Baker, B.; Hagerty, M.; Lomax, A.; Leifer, J. M.; Thies, D. A.; Schnackenberg, A.; Barrows, J.

    2015-12-01

    Tsunami Information technology Modernization (TIM) is a National Oceanic and Atmospheric Administration (NOAA) project to update and standardize the earthquake and tsunami monitoring systems currently employed at the U.S. Tsunami Warning Centers in Ewa Beach, Hawaii (PTWC) and Palmer, Alaska (NTWC). While this project was funded by NOAA to solve a specific problem, the requirements that the delivered system be both open source and easily maintainable have resulted in the creation of a variety of open source (OS) software packages. The open source software is now complete and this is a presentation of the OS Software that has been funded by NOAA for benefit of the entire seismic community. The design architecture comprises three distinct components: (1) The user interface, (2) The real-time data acquisition and processing system and (3) The scientific algorithm library. The system follows a modular design with loose coupling between components. We now identify the major project constituents. The user interface, CAVE, is written in Java and is compatible with the existing National Weather Service (NWS) open source graphical system AWIPS. The selected real-time seismic acquisition and processing system is open source SeisComp3 (sc3). The seismic library (libseismic) contains numerous custom written and wrapped open source seismic algorithms (e.g., ML/mb/Ms/Mwp, mantle magnitude (Mm), w-phase moment tensor, bodywave moment tensor, finite-fault inversion, array processing). The seismic library is organized in a way (function naming and usage) that will be familiar to users of Matlab. The seismic library extends sc3 so that it can be called by the real-time system, but it can also be driven and tested outside of sc3, for example, by ObsPy or Earthworm. To unify the three principal components we have developed a flexible and lightweight communication layer called SeismoEdex.

  7. Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

    PubMed Central

    Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.; Engelke, Udo F.; Boekhorst, Jos; Keegan, Kevin P.; Nielsen, Fiona G. G.; Betley, Jason; Weir, Jacqueline C.; Kingsbury, Zoya; Kluijtmans, Leo A. J.; Swinkels, Dorine W.; Venema, Koen; Tjalsma, Harold

    2016-01-01

    Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessed by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. Our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer. PMID:26779139

  8. Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma.

    PubMed

    Cai, Chen; Zhang, Jin; Li, Minyu; Wu, Zhen-Jie; Song, Ken H; Zhan, Tina W; Wang, Lin-Hui; Sun, Ying-Hao

    2016-06-01

    Renal cell carcinoma is among the leading causes of cancer-related death and was found to induce IL-10. We started by focusing on IL-10-secreting cells in tumor-infiltrating lymphocytes in renal cell carcinoma patients and observed that both CD3(+) T cells and CD19(+) B cells contributed to an elevated IL-10 expression. We then focused on IL-10-expressing B cells, and found that compared to non-IL-10-producing B cells, the IL-10-expressing B cells had significantly lower levels of CD19 and CD20 expression, a lack of IgM and IgD expression, while the level of CD27 was elevated. Moreover, culturing under unstimulated conditions resulted in higher antibody production by these IL-10-producing B cells than their peripheral blood counterparts, which strongly suggested that they are plasmablast-differentiating cells. Both IgA and IgG subtypes were found but IgA had a higher relative abundance in the tumor-infiltrating fraction. We then observed inverse correlations between the frequency of IL-10-producing B cells and pro-inflammatory cytokine-producing T cells and T cell proliferation. The expression of T cell exhaustion marker Tim-3, however, was upregulated in patients with high frequencies of IL-10-producing B cells. Moreover, supernatant from tumor B cells suppressed T cell inflammation. In addition, frequencies of IL-10-producing tumor-infiltrating B cells were inversely correlated with resected tumor size, and were higher in later stage tumors. Together, our data demonstrated that IL-10-producing B cells had plasmablast-differentiating phenotype, and could contribute to T cell immunosuppression in renal cell carcinoma.

  9. Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

    SciTech Connect

    Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.; Engelke, Udo F.; Boekhorst, Jos; Keegan, Kevin P.; Nielsen, Fiona G. G.; Betley, Jason; Weir, Jacqueline C.; Kingsbury, Zoya; Kluijtmans, Leo A. J.; Swinkels, Dorine W.; Venema, Koen; Tjalsma, Harold

    2016-01-06

    Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessed by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.

  10. Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

    DOE PAGES

    Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.; ...

    2016-01-06

    Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessedmore » by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.« less

  11. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    NASA Astrophysics Data System (ADS)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  12. Pedagogical Basis of DAS Formalism in Engineering Education

    ERIC Educational Resources Information Center

    Hiltunen, J.; Heikkinen, E.-P.; Jaako, J.; Ahola, J.

    2011-01-01

    The paper presents a new approach for a bachelor-level curriculum structure in engineering. The approach is called DAS formalism according to its three phases: description, analysis and synthesis. Although developed specifically for process and environmental engineering, DAS formalism has a generic nature and it could also be used in other…

  13. Evidence of Motor Programming Deficits in Children Diagnosed with DAS.

    ERIC Educational Resources Information Center

    Nijland, Lian; Maassen, Ben; van der Meulen, Sjoeke

    2003-01-01

    Five children with developmental apraxia of speech (DAS), 5 controls (ages 5-6), and 6 adults produced utterances in a normal condition and in a bite-block condition in which the mandible was in a fixed position. In children with DAS, the bite-block had large effects on coarticulatory patterns and vowel quality. (Contains references.) (Author/CR)

  14. Precise determination of δ88Sr in rocks, minerals, and waters by double-spike TIMS: A powerful tool in the study of chemical, geologic, hydrologic and biologic processes

    USGS Publications Warehouse

    Neymark, Leonid A.; Premo, Wayne R.; Mel'nikov, Nikolay N.; Emsbo, Poul

    2014-01-01

    We present strontium isotopic (88Sr/86Sr and 87Sr/86Sr) results obtained by 87Sr–84Sr double spike thermal ionization mass-spectrometry (DS-TIMS) for several standards as well as natural water samples and mineral samples of abiogenic and biogenic origin. The detailed data reduction algorithm and a user-friendly Sr-specific stand-alone computer program used for the spike calibration and the data reduction are also presented. Accuracy and precision of our δ88Sr measurements, calculated as permil (‰) deviations from the NIST SRM-987 standard, were evaluated by analyzing the NASS-6 seawater standard, which yielded δ88Sr = 0.378 ± 0.009‰. The first DS-TIMS data for the NIST SRM-607 potassium feldspar standard and for several US Geological Survey carbonate, phosphate, and silicate standards (EN-1, MAPS-4, MAPS-5, G-3, BCR-2, and BHVO-2) are also reported. Data obtained during this work for Sr-bearing solids and natural waters show a range of δ88Sr values of about 2.4‰, the widest observed so far in terrestrial materials. This range is easily resolvable analytically because the demonstrated external error (±SD, standard deviation) for measured δ88Sr values is typically ≤0.02‰. It is shown that the “true” 87Sr/86Sr value obtained by the DS-TIMS or any other external normalization method combines radiogenic and mass-dependent mass-fractionation effects, which cannot be separated. Therefore, the “true” 87Sr/86Sr and the δ87Sr parameter derived from it are not useful isotope tracers. Data presented in this paper for a wide range of naturally occurring sample types demonstrate the potential of the δ88Sr isotope tracer in combination with the traditional radiogenic 87Sr/86Sr tracer for studying a variety of biological, hydrological, and geological processes.

  15. Crystal structures of two bacterial 3-hydroxy-3-methylglutaryl-CoA lyases suggest a common catalytic mechanism among a family of TIM barrel metalloenzymes cleaving carbon-carbon bonds.

    PubMed

    Forouhar, Farhad; Hussain, Munif; Farid, Ramy; Benach, Jordi; Abashidze, Mariam; Edstrom, William C; Vorobiev, Sergey M; Xiao, Rong; Acton, Thomas B; Fu, Zhuji; Kim, Jung-Ja P; Miziorko, Henry M; Montelione, Gaetano T; Hunt, John F

    2006-03-17

    The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 A resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name "DRE-TIM metallolyases" for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and can

  16. Crystal Structures of Two Bacterial 3-Hydroxy-3-methylglutaryl-CoA Lyases Suggest a Common Catalytic Mechanism among a Family of TIM Barrel Metalloenzymes Cleaving Carbon-Carbon Bonds

    SciTech Connect

    Forouhar,F.; Hussain, M.; Farid, R.; Benach, J.; Abashidze, M.; Edstrom, W.; Vorobiev, S.; Montelione, G.; Hunt, J.; et al.

    2006-01-01

    The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 {angstrom} resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name 'DRE-TIM metallolyases' for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and

  17. Precise Crystallization Age of the Bushveld Complex, South Africa: Direct Dating of the Platiniferous Merensky Reef Using the Zircon U-Pb Chemical Abrasion ID-TIMS Technique

    NASA Astrophysics Data System (ADS)

    Scoates, J. S.; Friedman, R. M.

    2006-12-01

    Determining the age of the Bushveld Complex, the world's largest layered intrusion and host to the majority of the known resources of platinum group elements, chromium and vanadium, has been difficult given the very low abundance of U-bearing minerals in the ultramafic-mafic cumulate rocks that comprise the body. This study provides a precise crystallization age for this giant layered intrusion and associated PGE mineralization, and allows for a re-evaluation of the duration and areal extent of Bushveld-related magmatic activity. Abundant, clear and colorless, anhedral zircon grains were separated from a sample of pegmatoidal feldspathic orthopyroxenite collected from the Merensky Reef in the West Mine (Townlands Shaft), Rustenburg Section. Low-U (21-105 ppm) zircon occurs with interstitial biotite and is locally directly in contact with sulfide. The zircon grains were subjected to different pre-treatment methods (no pre-treatment, air abrasion, and chemical abrasion [CA]) and isotope ratios for individual grains were analyzed by ID-TIMS. U-Pb data for the unabraded and air-abraded grains, and leachates from the CA procedure, are slightly discordant (0.1-1.6%) and yield overlapping 207Pb/206Pb dates ranging from 2052.5 to 2058.9 Ma. For the CA zircon grains (n=6), all data are concordant and give a Concordia age of 2054.3 ± 2.5 Ma (2sd, decay-constant errors included), which is interpreted as the age of crystallization of the Merensky Reef. This age is within error of published ages for the overlying, and locally cross-cutting, Bushveld or Lebowa granite suite, which implies that the entire Bushveld Complex was emplaced within a 2-3 myr interval. Comparison with ages from satellite intrusions (e.g. Moshaneng, Botswana; Uitkomst, South Africa) indicates that the Bushveld magmatic event at ca. 2054 Ma was regionally extensive across the northern Kaapvaal Craton and is consistent with relatively rapid emplacement of mantle-derived magmas along the Thabazimbi

  18. Ejecta patterns of Meteor Crater, Arizona derived from the linear un-mixing of TIMS data and laboratory thermal emission spectra

    NASA Technical Reports Server (NTRS)

    Ramsey, Michael S.; Christensen, Philip R.

    1992-01-01

    Accurate interpretation of thermal infrared data depends upon the understanding and removal of complicating effects. These effects may include physical mixing of various mineralogies and particle sizes, atmospheric absorption and emission, surficial coatings, geometry effects, and differential surface temperatures. The focus is the examination of the linear spectral mixing of individual mineral or endmember spectra. Linear addition of spectra, for particles larger than the wavelength, allows for a straight-forward method of deconvolving the observed spectra, predicting a volume percent of each endmember. The 'forward analysis' of linear mixing (comparing the spectra of physical mixtures to numerical mixtures) has received much attention. The reverse approach of un-mixing thermal emission spectra was examined with remotely sensed data, but no laboratory verification exists. Understanding of the effects of spectral mixing on high resolution laboratory spectra allows for the extrapolation to lower resolution, and often more complicated, remotely gathered data. Thermal Infrared Multispectral Scanner (TIMS) data for Meteor Crater, Arizona were acquired in Sep. 1987. The spectral un-mixing of these data gives a unique test of the laboratory results. Meteor Crater (1.2 km in diameter and 180 m deep) is located in north-central Arizona, west of Canyon Diablo. The arid environment, paucity of vegetation, and low relief make the region ideal for remote data acquisition. Within the horizontal sedimentary sequence that forms the upper Colorado Plateau, the oldest unit sampled by the impact crater was the Permian Coconino Sandstone. A thin bed of the Toroweap Formation, also of Permian age, conformably overlays the Coconino. Above the Toroweap lies the Permian Kiabab Limestone which, in turn, is covered by a thin veneer of the Moenkopi Formation. The Moenkopi is Triassic in age and has two distinct sub-units in the vicinity of the crater. The lower Wupatki member is a fine

  19. Capturing the exhumation of a UHP terrane: CA-TIMS results from leucosomes and dikes exposed in the D'Entrecasteaux Islands, Papua New Guinea

    NASA Astrophysics Data System (ADS)

    Gordon, S. M.; Little, T. A.; Bowring, S. A.; Hacker, B. R.; DesOrmeau, J.

    2012-12-01

    Most UHP-HP terranes expose abundant migmatitic rocks. Partial melting of deeply subducted rocks has important rheological consequences for the deformational and exhumation history of these UHP rocks; therefore, it is critical to understand the precise timing of partial melting and crystallization relative to (U)HP metamorphism and to the exhumational history of the eclogites and surrounding gneisses. Of all UHP terranes, the D'Entrecasteaux Islands, southeastern Papua New Guinea (PNG) probably contains the best evidence for abundant syndeformational partial melting in the form of variably deformed leucosomes, dikes, and plutonic bodies. A series of leucosomes, dikes and eclogites were collected across three islands (Goodenough, Fergusson, and Normanby Islands) within PNG for U-Pb chemical-abrasion thermal-ionization mass spectrometry (CA-TIMS). Zircons extracted from eclogite at the UHP locality near Fergusson Island yield dates of ca. 5 Ma. The leucosomes and dikes collected from the UHP locality as well as from other parts of the dome exposed on Fergusson yield a two-stage melt crystallization history of ca. 3.5-3.0 Ma and 2.5-2.4 Ma. To the west on Goodenough Island and to the south on Normanby Island, a similar set of highly deformed leucosomes to weakly deformed dikes was collected and also yields a similar history: highly deformed dikes crystallized at ca. 4.5-4.1 Ma, whereas undeformed dikes yield dates of ca. 2.6-1.9 Ma. We interpret the older melt crystallization dates to record the timing at which the eclogite and gneisses were exhumed to lower crustal depths. The younger melt crystallization ages are interpreted to record stalling of this body at the base of the crust prior to doming and final exhumation of the rocks. Previous geochronometric results suggested a younging trend in the timing of metamorphism and cooling from east to west; however, our new zircon results reveal a very similar melt crystallization and exhumation history for the domes

  20. Interim Results from a Study of the Impacts of Tin (II) Based Mercury Treatment in a Small Stream Ecosystem: Tims Branch, Savannah River Site

    SciTech Connect

    Looney, Brian; BryanJr., Larry; Mathews, Teresa J; Peterson, Mark J; Roy, W Kelly; Jett, Robert T; Smith, John G

    2012-03-01

    A research team is assessing the impacts of an innovative mercury treatment system in Tims Branch, a small southeastern stream. The treatment system, installed in 2007, reduces and removes inorganic mercury from water using tin(II) (stannous) chloride addition followed by air stripping. The system results in discharge of inorganic tin to the ecosystem. This screening study is based on historical information combined with measurements of contaminant concentrations in water, fish, sediment, biofilms and invertebrates. Initial mercury data indicate that first few years of mercury treatment resulted in a significant decrease in mercury concentration in an upper trophic level fish, redfin pickerel, at all sampling locations in the impacted reach. For example, the whole body mercury concentration in redfin pickerel collected from the most impacted pond decreased approximately 72% between 2006 (pre-treatment) and 2010 (post-treatment). Over this same period, mercury concentrations in the fillet of redfin pickerel in this pond were estimated to have decreased from approximately 1.45 {micro}g/g (wet weight basis) to 0.45 {micro}g/g - a decrease from 4.8x to 1.5x the current EPA guideline concentration for mercury in fillet (0.3 {micro}g/g). Thermodynamic modeling, scanning electron microscopy, and other sampling data for tin suggest that particulate tin (IV) oxides are a significant geochemical species entering the ecosystem with elevated levels of tin measured in surficial sediments and biofilms. Detectable increases in tin in sediments and biofilms extended approximately 3km from the discharge location. Tin oxides are recalcitrant solids that are relatively non-toxic and resistant to dissolution. Work continues to develop and validate methods to analyze total tin in the collected biota samples. In general, the interim results of this screening study suggest that the treatment process has performed as predicted and that the concentration of mercury in upper trophic level

  1. Monazite and titanite U-Pb dating of Caledonian high-grade metamorphism in the Mid-Scandinavian Caledonides, Norway: a combined SHRIMP and ID-TIMS approach

    NASA Astrophysics Data System (ADS)

    Bingen, B.; Davis, W. J.; Hamilton, M. A.; Osmundsen, P. T.; Nordgulen, Ø.

    2003-04-01

    Crystals of metamorphic monazite commonly display age domains related to distinct episodes of growth or secondary crystallization. SHRIMP analyses of monazite in metapelite samples from north-central Norway, demonstrate homogeneous monazite populations, with unimodal age distribution. ID-TIMS analyses of single-grain or small fractions give reliable and precise estimates for the timing of monazite growth. Monazite, titanite and zircon U-Pb data constrain the duration of high-grade Scandian metamorphism to be 25 m.y. in this part of the orogen (426-401 Ma) and underscore the importance of late-Scandian extensional detachments as tectonometamorphic breaks between the Central Norway Basement Window (CNBW) and overlying nappes of the Upper (Köli nappes) and Uppermost Allochthons (Helgeland nappes). The CNBW is a core complex-like culmination trending ENE-WSW, made of high-pressure amphibolite-facies (locally granulite-facies) Proterozoic gneisses and in-folded supracrustal rocks. Monazite from a garnet-kyanite gneiss yields an age of 426 +/- 1 Ma reflecting conspicuous migmatization in the rock. Monazite in two garnet +/- kyanite gneisses with minor staurolite yields ages of 420 +/-2 and 403 +/-5 Ma. A deformed garnet-bearing granitic dyke yields a zircon intrusion age of 417 +/- 5 Ma. Titanite in four samples of calc-silicate gneiss and marble define a tight cluster between 403 and 401 +/-2 Ma. Titanite pre-dates top-WSW ductile extensional shearing along the Høybakken detachment in the SW of the CNBW and consequently constrains final exhumation of the window to be younger than 401 Ma. The Upper and Uppermost allochthons overlying the CNBW are made of greenshist to amphibolite-facies supracrustal rocks and plutonic complexes intruded at ca. 495, 480, 460, 445 and 428 Ma. Scandian translation of these outboard nappes onto Baltica occurred after 428 Ma. In the eastern Helgeland nappes, monazite in mica gneiss and titanite in amphibole gneiss and marble range from 431

  2. Tim Becomes an Eagle Scout.

    ERIC Educational Resources Information Center

    Fredericks, Bud

    1987-01-01

    A parent recounts his Downs Syndrome son's integration into a regular Boy Scout troop and subsequent earning of the Eagle rank. His Eagle project involved speaking about his disability in local elementary, junior high, and senior high schools. Policies of the Boy and Girl Scout organizations concerning disabled members are summarized. (CB)

  3. INTERIM RESULTS FROM A STUDY OF THE IMPACTS OF TIN(II) BASED MERCURY TREATMENT IN A SMALL STREAM ECOSYSTEM: TIMS BRANCH, SAVANNAH RIVER SITE

    SciTech Connect

    Looney, B.; Bryan, L.; Mathews, T.

    2012-03-30

    control measures have resulted in rapid responses in lake or reservoir fisheries (Joslin 1994, Turner and Southworth 1999; Orihel et al., 2007), but examples of similar responses in Hg-contaminated stream ecosystems are less common. Recent work suggests that stream systems may actually be more susceptible to mercury bioaccumulation than lakes, highlighting the need to better understand the ecological drivers of mercury bioaccumulation in stream-dwelling fish (Chasar et al. 2009, Ward et al. 2010). In the present study we examine the response of fish to remedial actions in Tims Branch, a point-source contaminated stream on the Department of Energy's (DOE) Savannah River Site in Aiken, South Carolina. This second order stream received inorganic mercury inputs at its headwaters from the 1950s-2000s which contaminated the water, sediments, and biota downstream. In 2007, an innovative mercury removal system using tin (II) chloride (stannous chloride, SnCl{sub 2}) was implemented at a pre-existing air stripper. Tin(II) reduces dissolved Hg (II) to Hg (0), which is removed by the air stripper. During this process, tin(II) is oxidized to tin (IV) which is expected to precipitate as colloidal tin(IV) oxides and hydroxides, particulate materials with relatively low toxicity (Hallas and Cooney, 1981, EPA 2002, ATSDR, 2005). The objectives of the present research are to provide an initial assessment of the net impacts of the tin(II) based mercury treatment on key biota and to document the distribution and fate of inorganic tin in this small stream ecosystem after the first several years of operating a full scale system. To support these objectives, we collected fish, sediment, water, invertebrates, and biofilm samples from Tims Branch to quantify the general behavior and accumulation patterns for mercury and tin in the ecosystem and to determine if the treatment process has resulted in: (1) a measurable beneficial impact on (i.e., decrease of) mercury concentration in upper trophic

  4. Twenty‐eight‐joint counts invalidate the DAS28 remission definition owing to the omission of the lower extremity joints: a comparison with the original DAS remission

    PubMed Central

    Landewé, R; van der Heijde, D; van der Linden, S; Boers, M

    2006-01-01

    Objective To compare 28 joint disease activity score (DAS28) remission with comprehensive joint count DAS remission in rheumatoid arthritis. Methods 620 actually measured paired observations of DAS28 and DAS were analysed in 155 patients. Discordant observations (either DAS or DAS28 below remission cut off level: 1.6 for DAS and 2.6 for DAS28) and concordant observations (both DAS and DAS28 below their remission cut off level) were analysed separately. Results 91 of 620 paired DAS observations (15%) were discordant; 87 (in 53 patients) comprised observations in which the DAS28 remission criterion, but not the DAS remission criterion, was met. The reverse was found in only four observations, which were therefore omitted. With the original DAS as standard, DAS28 sensitivity was 95% and specificity 84%. Probability plots showed a swollen joint count >0 in 75% of discordant pairs v 48% of concordant pairs. The same was found for total joint count (TJC >0 in 90% v 40%; median TJC, 0 v 6) and patient global assessment, but not for ESR. Individual joint analysis showed that 51% of discordant v 18% of concordant observations (p<0.0005) had involvement of lower extremity joints that are not included in the DAS28. Conclusions DAS remission is more conservative than DAS28 remission. Activity (tenderness and swelling) in joints not included in the reduced joint counts (ankles, feet) mainly account for the discrepancy between the two assessments. DAS28 remission at a cut off level of 2.6 has insufficient construct validity and should be used with caution in clinical practice and clinical trials. PMID:16219709

  5. DAS: A Data Management System for Instrument Tests and Operations

    NASA Astrophysics Data System (ADS)

    Frailis, M.; Sartor, S.; Zacchei, A.; Lodi, M.; Cirami, R.; Pasian, F.; Trifoglio, M.; Bulgarelli, A.; Gianotti, F.; Franceschi, E.; Nicastro, L.; Conforti, V.; Zoli, A.; Smart, R.; Morbidelli, R.; Dadina, M.

    2014-05-01

    The Data Access System (DAS) is a and data management software system, providing a reusable solution for the storage of data acquired both from telescopes and auxiliary data sources during the instrument development phases and operations. It is part of the Customizable Instrument WorkStation system (CIWS-FW), a framework for the storage, processing and quick-look at the data acquired from scientific instruments. The DAS provides a data access layer mainly targeted to software applications: quick-look displays, pre-processing pipelines and scientific workflows. It is logically organized in three main components: an intuitive and compact Data Definition Language (DAS DDL) in XML format, aimed for user-defined data types; an Application Programming Interface (DAS API), automatically adding classes and methods supporting the DDL data types, and providing an object-oriented query language; a data management component, which maps the metadata of the DDL data types in a relational Data Base Management System (DBMS), and stores the data in a shared (network) file system. With the DAS DDL, developers define the data model for a particular project, specifying for each data type the metadata attributes, the data format and layout (if applicable), and named references to related or aggregated data types. Together with the DDL user-defined data types, the DAS API acts as the only interface to store, query and retrieve the metadata and data in the DAS system, providing both an abstract interface and a data model specific one in C, C++ and Python. The mapping of metadata in the back-end database is automatic and supports several relational DBMSs, including MySQL, Oracle and PostgreSQL.

  6. Pedagogical basis of DAS formalism in engineering education

    NASA Astrophysics Data System (ADS)

    Hiltunen, J.; Heikkinen, E.-P.; Jaako, J.; Ahola, J.

    2011-03-01

    The paper presents a new approach for a bachelor-level curriculum structure in engineering. The approach is called DAS formalism according to its three phases: description, analysis and synthesis. Although developed specifically for process and environmental engineering, DAS formalism has a generic nature and it could also be used in other engineering fields. The motivation for this new curriculum structure originates from the urge to solve the problems that engineering education has faced during the past decades, e.g. student recruitment problems and dissatisfactory learning outcomes. The focus of this paper is on the structure of the curriculum but the content is also discussed when it has an effect on the structure and its implementation. The presented structure, i.e. DAS formalism, builds upon the ideas of some classical pedagogical theories, which have regularly been applied at course level but seldom used to solve curriculum-level issues.

  7. The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28).

    PubMed

    van Riel, P L C M

    2014-01-01

    In rheumatoid arthritis, disease activity cannot be measured using a single variable. The Disease Activity Score (DAS) has been developed as a quantitative index to be able to measure, study and manage disease activity in RA in daily clinical practice, clinical trials, and long term observational studies. The DAS is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and patient self-report of general health. Cut points were developed to classify patients in remission, as well as low, moderate, and severe disease activity in the 1990s. DAS-based EULAR response criteria were primarily developed to be used in clinical trials to classify individual patients as non-, moderate, or good responders, depending on the magnitude of change and absolute level of disease activity at the conclusion of the test.

  8. Time evolution of a rifted continental arc: Integrated ID-TIMS and LA-ICPMS study of magmatic zircons from the Eastern Srednogorie, Bulgaria

    NASA Astrophysics Data System (ADS)

    Georgiev, S.; von Quadt, A.; Heinrich, C. A.; Peytcheva, I.; Marchev, P.

    2012-12-01

    Eastern Srednogorie in Bulgaria is the widest segment of an extensive magmatic arc that formed by convergence of Africa and Europe during Mesozoic to Tertiary times. Northward subduction of the Tethys Ocean beneath Europe in the Late Cretaceous gave rise to a broad range of basaltic to more evolved magmas with locally associated Cu-Au mineralization along this arc. We used U-Pb geochronology of single zircons to constrain the temporal evolution of the Upper Cretaceous magmatism and the age of basement rocks through which the magmas were emplaced in this arc segment. High precision isotope dilution-thermal ionization mass spectrometry (ID-TIMS) was combined with laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) for spatial resolution within single zircon grains. Three tectono-magmatic regions are distinguished from north to south within Eastern Srednogorie: East Balkan, Yambol-Burgas and Strandzha. Late Cretaceous magmatic activity started at ~ 92 Ma in the northernmost East Balkan region, based on stratigraphic evidence and limited geochronology, with the emplacement of minor shallow intrusions and volcanic rocks onto pre-Cretaceous basement. In the southernmost Strandzha region, magmatism was initiated at ~ 86 Ma with emplacement of gabbroic to dioritic intrusions and related dikes into metamorphic basement rocks that have previously been overprinted by Jurassic-Lower Cretaceous metamorphism. The Yambol-Burgas region is an extensional basin between the East Balkan and the Strandzha regions, which broadens and deepens toward the Black Sea further east and is filled with a thick pile of marine sediments and submarine extrusive volcanic rocks accompanied by coeval intrusions. This dominantly mafic magmatism in the intermediate Yambol-Burgas region commenced at ~ 81 Ma and produced large volumes of potassium-rich magma until ~ 78 Ma. These shoshonitic to ultrapotassic basaltic to intermediate magmas formed by differentiation of ankaramitic (high

  9. Structure of L-Xylulose-5-Phosphate 3-Epimerase (UlaE) from the Anaerobic L-Ascorbate Utilization Pathway of Escherichia coli: Identification of a Novel Phosphate Binding Motif within a TIM Barrel Fold

    SciTech Connect

    Shi, Rong; Pineda, Marco; Ajamian, Eunice; Cui, Qizhi; Matte, Allan; Cygler, Miroslaw

    2009-01-15

    Three catabolic enzymes, UlaD, UlaE, and UlaF, are involved in a pathway leading to fermentation of L-ascorbate under anaerobic conditions. UlaD catalyzes a {beta}-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway. We describe here crystallographic studies of UlaE from Escherichia coli O157:H7 that complete the structural characterization of this pathway. UlaE has a triosephosphate isomerase (TIM) barrel fold and forms dimers. The active site is located at the C-terminal ends of the parallel {beta}-strands. The enzyme binds Zn{sup 2+}, which is coordinated by Glu155, Asp185, His211, and Glu251. We identified a phosphate-binding site formed by residues from the {beta}1/{alpha}1 loop and {alpha}3' helix in the N-terminal region. This site differs from the well-characterized phosphate-binding motif found in several TIM barrel superfamilies that is located at strands {beta}7 and {beta}8. The intrinsic flexibility of the active site region is reflected by two different conformations of loops forming part of the substrate-binding site. Based on computational docking of the L-xylulose 5-phosphate substrate to UlaE and structural similarities of the active site of this enzyme to the active sites of other epimerases, a metal-dependent epimerization mechanism for UlaE is proposed, and Glu155 and Glu251 are implicated as catalytic residues. Mutation and activity measurements for structurally equivalent residues in related epimerases supported this mechanistic proposal.

  10. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation

    PubMed Central

    Connell, Bridgette Janine; Chang, Sui-Yuan; Prakash, Ekambaranellore; Yousfi, Rahima; Mohan, Viswaraman; Posch, Wilfried; Wilflingseder, Doris; Moog, Christiane; Kodama, Eiichi N.; Clayette, Pascal; Lortat-Jacob, Hugues

    2016-01-01

    Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1–7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1. PMID:27788205

  11. Improved 206Pb/238U microprobe geochronology by the monitoring of a trace-element-related matrix effect; SHRIMP, ID-TIMS, ELA-ICP-MS and oxygen isotope documentation for a series of zircon standards

    USGS Publications Warehouse

    Black, L.P.; Kamo, S.L.; Allen, C.M.; Davis, D.W.; Aleinikoff, J.N.; Valley, J.W.; Mundil, R.; Campbell, I.H.; Korsch, R.J.; Williams, I.S.; Foudoulis, C.

    2004-01-01

    Precise isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) documentation is given for two new Palaeozoic zircon standards (TEMORA 2 and R33). These data, in combination with results for previously documented standards (AS3, SL13, QGNG and TEMORA 1), provide the basis for a detailed investigation of inconsistencies in 206Pb/238U ages measured by microprobe. Although these ages are normally consistent between any two standards, their relative age offsets are often different from those established by ID-TIMS. This is true for both sensitive high-resolution ion-microprobe (SHRIMP) and excimer laser ablation-inductively coupled plasma-mass spectrometry (ELA-ICP-MS) dating, although the age offsets are in the opposite sense for the two techniques. Various factors have been investigated for possible correlations with age bias, in an attempt to resolve why the accuracy of the method is worse than the indicated precision. Crystallographic orientation, position on the grain-mount and oxygen isotopic composition are unrelated to the bias. There are, however, striking correlations between the 206Pb/238U age offsets and P, Sm and, most particularly, Nd abundances in the zircons. Although these are not believed to be the primary cause of this apparent matrix effect, they indicate that ionisation of 206Pb/238U is influenced, at least in part, by a combination of trace elements. Nd is sufficiently representative of the controlling trace elements that it provides a quantitative means of correcting for the microprobe age bias. This approach has the potential to reduce age biases associated with different techniques, different instrumentation and different standards within and between laboratories. Crown Copyright ?? 2004 Published by Elsevier B.V. All rights reserved.

  12. On the Law of Inertia. Translation of: Ueber das Beharrungsgesetz

    NASA Astrophysics Data System (ADS)

    Lange, Ludwig

    2014-04-01

    This article is a translation of Ludwig Lange: "Ueber das Beharrungsgesetz" in: Berichte ueber Verhandlungen der Koenigl. Saechsischen Gesellschaft der Wissenschaften, math.-physik. Klasse (Leipzig, 1885), SS. 333-351. Translated by Herbert Pfister, Institut für Theoretische Physik, Universität Tübingen, Auf der Morgenstelle 14, 72076 Tübingen, Germany; herbert.pfister@uni-tuebingen.de. Kind assistance by Julian Barbour is acknowledged.

  13. U-Pb (ID-TIMS) baddeleyite ages and paleomagnetism of 1.79 and 1.59 Ga tholeiitic dyke swarms, and position of the Rio de la Plata Craton within the Columbia supercontinent

    NASA Astrophysics Data System (ADS)

    Teixeira, Wilson; D'Agrella-Filho, Manoel S.; Hamilton, Mike A.; Ernst, Richard E.; Girardi, Vicente A. V.; Mazzucchelli, Maurizio; Bettencourt, Jorge S.

    2013-08-01

    The Tandilia Terrane (southernmost fringe of the Rio de la Plata Craton) is an igneous and metamorphic complex produced by an accretionary orogeny (2.25-2.02 Ga). Calc-alkaline acidic dykes with E-W strike and a major shear zone with similar orientation are related with the late orogeny stage, as supported by field relations. In a previous study the acid dykes gave 40A-39Ar ages of 2007 ± 24 Ma to 2020 ± 24 Ma. A N and NW trending tholeiitic dyke swarm (Tandil swarm) is also present in the Tandilia Terrane. One sample from the NW-trending subset previously gave a U-Pb (ID-TIMS) baddeleyite age of 1588 ± 11 Ma. New precise U-Pb (ID-TIMS) baddeleyite dating of both N- and NW-trending Tandil dykes yielded crystallization ages of 1589 ± 3 Ma, 1588 ± 3 Ma and 1588 ± 3 Ma. Significantly older tholeiitic dykes known as the Florida swarm occur in the Northern Rio de la Plata Craton, for which a U-Pb (ID-TIMS) baddeleyite age of 1790 ± 5 Ma was previously reported. Consequently intermittent rifting (1.79, 1.59 Ga) took place after tectonic stabilization of the late Paleoproterozoic lithosphere (proto-Rio de la Plata Craton). The available geochemical data for the 1.59 Ga Tandil dykes define low- and high-TiO2 trends, although, only the low-TiO2 subgroup is firmly dated. Both the Tandil and Florida dykes have geochemical and Nd-Sr characteristics consistent with derivation from heterogeneous mantle sources that underwent metasomatic effects. The Tandil dykes may be linked with the 1.57 ± 0.02 Ga Capivarita anorthosite which occurs to the east of the northern part of the craton. Correlatives on other crustal blocks may include those in Baltica such as bimodal rock association (including the Breven-Hällefors and Åland-Åboland diabase dykes) and in the reconstructed Gawler Craton/NW Laurentia dolerites, bimodal magmatism and IOCG deposits. Contemporary within-plate bimodal associations are also present in the SW Amazonian Craton. Paleomagnetic data for the 1790 Ma

  14. Statistical Quality Control of Moisture Data in GEOS DAS

    NASA Technical Reports Server (NTRS)

    Dee, D. P.; Rukhovets, L.; Todling, R.

    1999-01-01

    A new statistical quality control algorithm was recently implemented in the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The final step in the algorithm consists of an adaptive buddy check that either accepts or rejects outlier observations based on a local statistical analysis of nearby data. A basic assumption in any such test is that the observed field is spatially coherent, in the sense that nearby data can be expected to confirm each other. However, the buddy check resulted in excessive rejection of moisture data, especially during the Northern Hemisphere summer. The analysis moisture variable in GEOS DAS is water vapor mixing ratio. Observational evidence shows that the distribution of mixing ratio errors is far from normal. Furthermore, spatial correlations among mixing ratio errors are highly anisotropic and difficult to identify. Both factors contribute to the poor performance of the statistical quality control algorithm. To alleviate the problem, we applied the buddy check to relative humidity data instead. This variable explicitly depends on temperature and therefore exhibits a much greater spatial coherence. As a result, reject rates of moisture data are much more reasonable and homogeneous in time and space.

  15. M-DAS: System for multispectral data analysis. [in Saginaw Bay, Michigan

    NASA Technical Reports Server (NTRS)

    Johnson, R. H.

    1975-01-01

    M-DAS is a ground data processing system designed for analysis of multispectral data. M-DAS operates on multispectral data from LANDSAT, S-192, M2S and other sources in CCT form. Interactive training by operator-investigators using a variable cursor on a color display was used to derive optimum processing coefficients and data on cluster separability. An advanced multivariate normal-maximum likelihood processing algorithm was used to produce output in various formats: color-coded film images, geometrically corrected map overlays, moving displays of scene sections, coverage tabulations and categorized CCTs. The analysis procedure for M-DAS involves three phases: (1) screening and training, (2) analysis of training data to compute performance predictions and processing coefficients, and (3) processing of multichannel input data into categorized results. Typical M-DAS applications involve iteration between each of these phases. A series of photographs of the M-DAS display are used to illustrate M-DAS operation.

  16. New Perspectives on the Marine Strontium Isotope Record of the last 27 Ma from delta 88/86Sr and 87Sr/86Sr Systematics Using the TIMS Sr-Double-Spike Technique

    NASA Astrophysics Data System (ADS)

    Liebetrau, V.; Eisenhauer, A.; Krabbenhoeft, A.; Fietzke, J.; Rueggeberg, A.; Guers, K.

    2008-12-01

    Applying a recently developed Sr-double spike the Sr-isotope fractionation for both 88Sr/86Sr and 87Sr/86Sr ratios in water and carbonates can now precisely be determined with the TIMS- technique. Repeated measurements of standard materials (NIST SRM 987, IAPSO seawater standard, JCp-1 carbonate standard) showed that δ 88Sr/86Sr (reported as δ 88/86Sr=((88Sr/86Sr)sample/(88Sr/86Sr)NBS987)-1)*1000) and 87Sr/86Sr ratios can be determined with an external reproducibility in the order of better than 20 ppm and about 6 ppm, respectively, for NIST SRM 987, IAPSO and JCp-1, respectively. Using the double spike TIMS technique the statistical error for determination of δ 88/86Sr is reaching a whole procedure reproducibility of about 15 ppm. All standard measurements are in general accord with previous observations (1,2) indicating that δ 88/86Srseawater and 87Sr/86Srseawater is about 0.39±0.02 ‰ and 0.709285(6) , (n=12), respectively, and that the marine carbonates being isotopically lighter than seawater (JCp-1, δ 88Sr/86Sr: 0.20±0.02; 87Sr/86Sr : 0.709219(6); n=3). Note, that also 87Sr/86Sr carbonate ratios is isotopically about 70 ppm lighter than seawater as expected from isotope fractionation during the precipitation of calcium carbonates (1). For a first application of our double spike on 13 bulk carbonate samples of aragonitic composition, representing marine shallow water mollusks (0 to 100m water depth), it has been shown that their bio- stratigraphic ages are in accordance with the classical Strontium isotope stratigraphy (SIS) after McArthur and Howarth (2004). The samples span an age range from the the Late Oligocene to Pleistocene (about 27 Ma). The δ 88Sr/86Sr-record shows variations in the order of about 0.2 ‰. The 87Sr/86Srseawater record tends to show higher values compared to the classical normalized 87Sr/86Sr record. The offset is not constant rather correlated to the 88Sr/86Sr ratios. Preliminary interpretation take seawater temperature

  17. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis.

    PubMed

    van Riel, Piet L C M; Renskers, Lisanne

    2016-01-01

    In rheumatoid arthritis (RA), disease activity cannot be measured in all individual patients according to a single variable. The Disease Activity Score (DAS) and the DAS28 have been developed to measure disease activity in RA both in daily clinical practice as well as in clinical trials on a group as well as individual level. The DAS/DAS28 is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health. The DAS-based EULAR response criteria were primarily developed to be used in clinical trials. The EULAR response criteria classify individual patients as non-, moderate, or good responders, dependent on the magnitude of change and level of disease activity reached. In addition, already in the early nineties, cut points were developed to categorise patients in remission. The DAS28 is incorporated in several electronic patient records and web-based systems for monitoring purposes in daily clinical practice. In addition to this, it is being used in combination with patient-reported outcome measures (PROMs) to facilitate self-monitoring.

  18. Detecting Changes Following the Provision of Assistive Devices: Utility of the WHO-DAS II

    ERIC Educational Resources Information Center

    Raggi, Alberto

    2010-01-01

    The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a non-disease-specific International Classification of Functioning, Disability, and Health-based disability assessment instrument developed to measure activity limitations and restrictions to participation. The aim of this pilot study is to evaluate WHO-DAS II…

  19. Psychometric Properties of the Disability Assessment Schedule (DAS) for Behavior Problems: An Independent Investigation

    ERIC Educational Resources Information Center

    Tsakanikos, Elias; Underwood, Lisa; Sturmey, Peter; Bouras, Nick; McCarthy, Jane

    2011-01-01

    The present study employed the Disability Assessment Schedule (DAS) to assess problem behaviors in a large sample of adults with ID (N = 568) and evaluate the psychometric properties of this instrument. Although the DAS problem behaviors were found to be internally consistent (Cronbach's [alpha] = 0.87), item analysis revealed one weak item…

  20. Characterization of depositional age and structure of sedimentary successions by U-Pb TIMS and LA-ICP-MS dating of volcanic horizons and detrital zircons: an example from the western Trondheim Nappe Complex, Scandinavian Caledonides

    NASA Astrophysics Data System (ADS)

    Gasser, Deta; Grenne, Tor; Corfu, Fernando; Eivind Augland, Lars

    2016-04-01

    Revealing the absolute depositional age of non-fossiliferous sedimentary successions represents a long-lasting challenge in Earth Sciences. Lacking age control hampers the correct interpretation of the temporal evolution of depositional systems, and, if deformed, of the architecture of fold-and-thrust belts. Dating of detrital zircons within clastic sedimentary successions has over the past decades become a popular method to approximate the absolute depositional age and to characterize the source areas of such rocks. If combined with other geochronological information, such as dating of contemporaneous volcanic horizons, a much better resolution of the stratigraphy and structure of non-fossiliferous sedimentary successions can be achieved. The western Trondheim nappe complex in the central Scandinavian Caledonides is a classical area in this respect. On top of Late Cambrian to Early Ordovician ophiolitic fragments, various volcanic, volcano-clastic and clastic successions tell a complex story of island-arc formation, ocean closure and continent collision. Several famous fossil horizons indicate deposition during the Middle to Upper Ordovician (ca. 470-445 Ma), but large areas lack an absolute age control and several contrasting stratigraphic schemes and structural interpretations have been presented in the past. In this contribution we present the results of LA-ICP-MS detrital U-Pb zircon dating of clastic horizons as well as U-Pb TIMS zircon dating of volcanic horizons and magmatic clasts in conglomerates in order to characterize the depositional age and structure of the western Trondheim nappe complex in more detail. Together with field observations, including way up criteria, the zircon data enable significant revisions of existing stratigraphic and structural models. At least four (volcano-)sedimentary successions can be distinguished above the ca. 480-485 Ma greenstones: (1) ca. 470-463 Ma shales, limestones and andesitic porphyrites (Hølonda and Fanabekken

  1. Learning to Teach--Tim's Story

    ERIC Educational Resources Information Center

    Rowland, Tim

    2006-01-01

    This article is both a sequel and a companion to the account by Gill Hatch, published in "MT196," of her experience in her first teaching post--as a College of Education Assistant Lecturer. A chance remark by Gill in 2001 made the author aware that their careers as mathematics teachers had begun in similar environments. They set about compiling a…

  2. Consumer Feedback: Tiny Tim Is Dead!

    ERIC Educational Resources Information Center

    Remmes, Harold

    1974-01-01

    In a paper delivered (June, 1974) at the Nationwide Staff Meeting of the National Easter Seal Society for Crippled Children and Adults, the author stresses the need for consumer involvement in agencies providing services to the handicapped. (LS)

  3. Molecular Nanoparks for CWAs, TICs, and TIMs

    DTIC Science & Technology

    2012-12-11

    Organometallic Complexes , Journal of the American Chemical Society, (07 2010): 0. doi: 10.1021/ja103016y 12/04/2012 4.00 Christian J. Doonan, David J...Received Paper TOTAL: Books Number of Manuscripts: Received Paper TOTAL: Patents Submitted 20120259135, O. M. Yaghi, C. J. Doonan, H. Deng, Complex mixed...metal effects on gas selectivity, we are extending our strategy to create metalated nanoparks; MOF with (i) covalently bound organometallic complexes

  4. Hydrostatic shoe bearing system for the TIM

    NASA Astrophysics Data System (ADS)

    Ruiz Schneider, Elfego; Sohn, Erika; Quiros-Pacheco, Fernando; Godoy, Javier; Farah Simon, Alejandro; Quintanilla, R.; Soto, P.; Salas, Luis; Cruz-Gonzales, Irene

    2000-08-01

    We present an active, low cost hydrostatic shoe bearing system for the Mexican Infrared Telescope which solves the suspension and motion of a 100 ton, 7.8 m telescope. Different geometries are analyzed to optimize the shoe's pressure print. These designs offer a self-adjusting action between the shoe's sliding path and the girth track. Different parameters such as pressure, temperature and proximity are measured and implemented into a control system in order to stabilize the bearing from the fluid's thermal viscosity effects. A simple method for fluid injection is discussed.

  5. A Waterman's Journey: Tim Junkin's Bloodsworth

    ERIC Educational Resources Information Center

    Ward, Nathan

    2004-01-01

    Before he was wrongly sent to death row for the rape and murder of a nine-year-old girl in 1984, Kirk Bloodsworth enjoyed the life of a Chesapeake Bay waterman. Convicted largely on the testimony of a seven- and a ten-year-old eyewitness, by 1989 Johnson had exhausted almost every legal option available--after winning a new trial, he was convicted…

  6. DasR positively controls monensin production at two-level regulation in Streptomyces cinnamonensis.

    PubMed

    Zhang, Yue; Lin, Chun-Yan; Li, Xiao-Mei; Tang, Zheng-Kun; Qiao, Jianjun; Zhao, Guang-Rong

    2016-12-01

    The polyether ionophore antibiotic monensin is produced by Streptomyces cinnamonensis and is used as a coccidiostat for chickens and growth-promoting agent for cattle. Monensin biosynthetic gene cluster has been cloned and partially characterized. The GntR-family transcription factor DasR regulates antibiotic production and morphological development in Streptomyces coelicolor and Saccharopolyspora erythraea. In this study, we identified and characterized the two-level regulatory cascade of DasR to monensin production in S. cinnamonensis. Forward and reverse genetics by overexpression and antisense RNA silence of dasR revealed that DasR positively controls monensin production under nutrient-rich condition. Electrophoresis mobility shift assay (EMSA) showed that DasR protein specifically binds to the promoter regions of both pathway-specific regulatory gene monRII and biosynthetic genes monAIX, monE and monT. Semi-quantitative RT-PCR further confirmed that DasR upregulates the transcriptional levels of these genes during monensin fermentation. Subsequently, co-overexpressed dasR with pathway-specific regulatory genes monRI, monRII or monH greatly improved monensin production.

  7. Compositional safety of herbicide-tolerant DAS-81910-7 cotton.

    PubMed

    Herman, Rod A; Fast, Brandon J; Johnson, Tempest Y; Sabbatini, Jane; Rudgers, Gary W

    2013-11-27

    DAS-81910-7 cotton is a transgenic event that was transformed to contain the aad-12 and pat genes. These genes code for the AAD-12 and PAT proteins, which confer tolerance to the herbicides 2,4-D and glufosinate, respectively. Crop composition studies were conducted with DAS-81910-7 cotton (both nonsprayed and sprayed with 2,4-D and glufosinate) to comply with requirements of regulatory authorities responsible for evaluating crop safety. Results indicate compositional equivalence between DAS-81910-7 cottonseed and nontransgenic cottonseed and between sprayed and nonsprayed DAS-81910-7 cottonseed. This study builds on the results from many prior studies which support the conclusion that transgenesis is less likely to unexpectedly alter the composition of crops as compared with traditional breeding.

  8. Isotope age of the rare metal pegmatite formation in the Kolmozero-Voron'ya greenstone belt (Kola region of the Fennoscandian shield): U-Pb (TIMS) microlite and tourmaline dating

    NASA Astrophysics Data System (ADS)

    Kudryashov, Nikolay; Lyalina, Ludmila; Mokrushin, Artem; Zozulya, Dmitry; Groshev, Nikolay; Steshenko, Ekaterina; Kunakkuzin, Evgeniy

    2016-04-01

    The Kolmozero-Voron'ya greenstone belt is located in the central suture zone, which separates the Murmansk block from the Central-Kola and the Keivy blocks. The belt is represented by volcano-sedimentary rocks of Archaean age of 2.9-2.5 Ga. Rare metal pegmatites (Li, Cs with accessory Nb, Ta, and Be) occur among amphibolite and gabbroid intrusions in the northwestern and southeastern parts of the belt. According to the Rb-Sr data, the age of pegmatites was considered to be 2.7 Ga. Until recently there was no generally accepted point of view on the origin of pegmatites. Now we have isotopic data for a range of rock complexes that could pretend to be parental granites for the rare metal pegmatites. These are granodiorites with the zircon age of 2733±Ma, and microcline and tourmaline granites, which Pb-Pb isochronal age on tourmaline from the tourmaline granite located near the deposit is estimated to be 2520±70 Ma. The pegmatite field of the Vasin Myl'k deposit with the lepidolite--albite--microcline--spodumene--pollucite association is located among amphibolites in the northwestern part of the belt. The deposit is represented by subparallel low-angle zoned veins up to 220 m long and 5 m thick dipping in the southeastern direction at an angle of 10° too 30°. The minerals of the columbite--tonalite group from Vasin Myl'k deposit include microlite, simpsonite, and torolite, and are the oldest among different minerals represented by several generations in pegmatites under consideration. Zircons from the pegmatites are mostly represented by crystals with the structure affected by the action of fluids that put certain restrictions on its use as a geochronometer of the crystallization process. Microlite from the pegmatite taken from the dump of a prospecting drill hole was used for U--Pb (TIMS). The mineral is represented by 0.5--1.0 mm long euhedral octahedral crystals. It is brown in color, and transparent. The microlite crystals were preliminarily cleaned from

  9. Development of a Driver Alert System (DAS) for the Bradley Fighting Vehicle

    DTIC Science & Technology

    1988-07-01

    FIGHTING VEHICLE The survivability of a Bradley Fighting Vehicle (BFV) depends, in large part, on rapid response and movement in changing battle conditions...ARI Research Note 88-73 I6 0 Development of aDriver AertSystem CO (DAS) for the Bradley Fighting Vehicle * David F. Champion, Paul R. Roberson, and...System (DAS) Final Report for the Bradley Fighting Vehicle September 85 - September 87 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(s) 6. CONTRACT OR GRANT

  10. Phase 1 Clinical Trials of DAS181, an Inhaled Sialidase, in Healthy Adults

    PubMed Central

    Zenilman, Jonathan M.; Fuchs, Edward J.; Hendrix, Craig W.; Radebaugh, Christine; Jurao, Robert; Nayak, Seema U.; Hamilton, Robert G.; Griffiss, J. McLeod

    2015-01-01

    DAS181, (study drug, Fludase®) was developed for treatment of influenza and parainfluenza infections. Delivered by inhalation, DAS181 cleaves sialic acid receptors from respiratory epithelial cells. Treatment of influenza for three days with DAS181 reduced viral shedding. To increase deposition in the upper airways and decrease systemic absorption, the particle size was increased to 10 microns. We conducted two Phase I trials with three cohorts, randomized 2:1, active drug to placebo. The initial cohort got a single 20 mg dose of DAS181, or placebo; the second, 20 mg DAS181 or placebo for 10 days, and the third got 20 mg of DAS181or placebo for 3 days. Formulations differed slightly in their excipients. Subjects in the 1- and 3-day cohorts completed dosing without serious adverse events. Two subjects in the 10-day cohort stopped at Day 9 after developing respiratory and systemic symptoms, and a third experienced a decrease in FEV1 (Forced Expiratory Volume in 1 second) after the 9th dose and a further decline after the 10th dose. Plasma DAS181, in the 10-day cohort, peaked and began falling before the last dose. Antibodies, predominately IgG with neutralizing activity, were detected in 15/18 subjects by Day 30. The highest IgG concentrations were in the 10-day cohort. The respiratory adverse events occurring after seven days and rapid drug clearance during continued dosing are consistent with the induction of DAS181 antibodies. This could preclude use of this medication for longer than seven days or for repeated courses. (These studies have been registered at ClinicalTrials.gov under registration nos. NCT 00527865 and NCT 01651494.) PMID:26391974

  11. Phase 1 clinical trials of DAS181, an inhaled sialidase, in healthy adults.

    PubMed

    Zenilman, Jonathan M; Fuchs, Edward J; Hendrix, Craig W; Radebaugh, Christine; Jurao, Robert; Nayak, Seema U; Hamilton, Robert G; McLeod Griffiss, J

    2015-11-01

    DAS181, (study drug, Fludase®) was developed for treatment of influenza and parainfluenza infections. Delivered by inhalation, DAS181 cleaves sialic acid receptors from respiratory epithelial cells. Treatment of influenza for three days with DAS181 reduced viral shedding. To increase deposition in the upper airways and decrease systemic absorption, the particle size was increased to 10μm. We conducted two Phase I trials with three cohorts, randomized 2:1, active drug to placebo. The initial cohort got a single 20mg dose of DAS181, or placebo; the second, 20mg DAS181 or placebo for 10days, and the third got 20mg of DAS181 or placebo for 3days. Formulations differed slightly in their excipients. Subjects in the 1- and 3-day cohorts completed dosing without serious adverse events. Two subjects in the 10-day cohort stopped at Day 9 after developing respiratory and systemic symptoms, and a third experienced a decrease in FEV1 (Forced Expiratory Volume in 1s) after the 9th dose and a further decline after the 10th dose. Plasma DAS181, in the 10-day cohort, peaked and began falling before the last dose. Antibodies, predominately IgG with neutralizing activity, were detected in 15/18 subjects by Day 30. The highest IgG concentrations were in the 10-day cohort. The respiratory adverse events occurring after seven days and rapid drug clearance during continued dosing are consistent with the induction of DAS181 antibodies. This could preclude use of this medication for longer than seven days or for repeated courses. (These studies have been registered at ClinicalTrials.gov under registration Nos. NCT 00527865 and NCT 01651494.).

  12. VIIRS ocean color data visualization and processing with IDL-based NOAA-SeaDAS

    NASA Astrophysics Data System (ADS)

    Wang, Xiaolong; Liu, Xiaoming; Jiang, Lide; Wang, Menghua; Sun, Junqiang

    2014-11-01

    The NOAA Sea-viewing Data Analysis System (NOAA-SeaDAS) is an Interactive Data Language (IDL)-based satellite data visualization, analysis, and processing system based on the version 6.4 of the NASA's Sea-viewing Wide Field-ofview (SeaWiFS) Data Analysis System (SeaDAS) released in 2012. NOAA-SeaDAS inherited all the original functionalities of SeaDAS 6.4 and was upgraded with many new functions and new sensor supports, particularly the support of the Visible Infrared Imaging Radiometer Suite (VIIRS) onboard the Suomi National Polar-Orbiting Partnership (SNPP). The main goal of the NOAA-SeaDAS development is primarily in support of NOAA ocean color team's calibration and validation activities. The current version of NOAA-SeaDAS can visualize, analyze, and process VIIRS Sensor Data Records (SDR or Level-1B data) produced by the NOAA Interface Data Processing System (IDPS), ocean color Environmental Data Records (EDR or Level-2 data) produced by the NOAA Multi-Sensor Level-1 to Level- 2 (MSL12) ocean color data processing system, and Level-3 data binned or mapped from Level-2 data produced by NOAA-MSL12. NOAA-SeaDAS is currently serving an active IDL user group at NOAA and will serve other institutions and universities in the future. The goal is to allow various scientific users to visualize, analyze, and process VIIRS data from Level-1B through Level-2 and Level-3. In addition, NOAA-SeaDAS can also visualize satellite images from the Korean Geostationary Ocean Color Imager (GOCI), as well as many other satellite ocean color sensors, e.g., SeaWiFS, the Moderate Resolution Imaging Spectroradiometer (MODIS), etc. NOAA-SeaDAS is under constant development to create new system functionalities and enhance user experience. With constantly increasing volume in the global ocean color data archive, NOAA-SeaDAS will play an important role in support of global marine environment data analysis and various scientific applications.

  13. Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein.

    PubMed

    Triana-Baltzer, Gallen B; Gubareva, Larisa V; Klimov, Alexander I; Wurtman, David F; Moss, Ronald B; Hedlund, Maria; Larson, Jeffrey L; Belshe, Robert B; Fang, Fang

    2009-11-06

    Antiviral drug resistance for influenza therapies remains a concern due to the high prevalence of H1N1 2009 seasonal influenza isolates which display H274Y associated oseltamivir-resistance. Furthermore, the emergence of novel H1N1 raises the potential that additional reassortments can occur, resulting in drug resistant virus. Thus, additional antiviral approaches are urgently needed. DAS181 (Fludase), a sialidase fusion protein, has been shown to have inhibitory activity against a large number of seasonal influenza strains and a highly pathogenic avian influenza (HPAI) strain (H5N1). Here, we examine the in vitro activity of DAS181 against a panel of 2009 oseltamivir-resistant seasonal H1N1 clinical isolates. The activity of DAS181 against nine 2009, two 2007, and two 2004 clinical isolates of seasonal IFV H1N1 was examined using plaque number reduction assay on MDCK cells. DAS181 strongly inhibited all tested isolates. EC50 values remained constant against isolates from 2004, 2007, and 2009, suggesting that there was no change in DAS181 sensitivity over time. As expected, all 2007 and 2009 isolates were resistant to oseltamivir, consistent with the identification of the H274Y mutation in the NA gene of all these isolates. Interestingly, several of the 2007 and 2009 isolates also exhibited reduced sensitivity to zanamivir, and accompanying HA mutations near the sialic acid binding site were observed. DAS181 inhibits IFV that is resistant to NAIs. Thus, DAS181 may offer an alternative therapeutic option for seasonal or pandemic IFVs that become resistant to currently available antiviral drugs.

  14. BOOK REVIEW: Geheimnisvolles Universum - Europas Astronomen entschleiern das Weltall

    NASA Astrophysics Data System (ADS)

    Duerbeck, H. W.; Lorenzen, D. H.

    2002-12-01

    The 25th birthday of ESO, in 1987, was celebrated by the publication of an illustrated popular book, "Exploring the Southern Sky" (Springer-Verlag 1987), which also saw editions in Danish, English, French, German, and Spanish. Written and illustrated by the ESO staff members Svend Laustsen, Claus Madsen and Richard M. West, its many pictures were mainly taken with the ESO 3.6m and Schmidt telescopes. The structure of the book - perhaps at that time somewhat unusual - started with things far away (Universe and galaxies), zoomed in to the Milky Way, and finally reached the Solar System (with a concluding chapter dealing with the La Silla observatory). Now, with the 4 units of the Very Large Telescope in full operation, and on the occasion of ESO's 40th birthday, another jubilee book has appeared: "Geheimnisvolles Universum: Europas Astronomen entschleiern das Weltall", written by the science journalist Dirk H. Lorenzen, of Hamburg, Germany, and prefaced by Catherine Cesarsky, Director General of ESO. Presumably, this book will also soon become available in more languages spoken in ESO member countries. Thus it may be worthwhile to review the first edition, although some readers may like to wait for more easily accessible editions. Before going into details, let me first mention that I find this a very impressing book, great to look at and refreshing to read. With ESO seen through the eyes of a visitor, things gain a perspective that is quite different from that of the previous book, and at least as attractive. It comes as no surprise that the book starts with a visit of ESO's showcase, the Paranal Observatory, and the writer not only notes down his own impressions, but also cites statements of some of the many people that keep Paranal going - technicians and staff astronomers. This mixture of texts provides a good impression of the operations at a large observatory for the general reader. The two more 'astronomical' parts that follow deal with star and planet

  15. Amerikas Einschätzung der deutschen Atomforschung: Das deutsche Uranprojekt

    NASA Astrophysics Data System (ADS)

    Walker, Mark

    2002-07-01

    Die amerikanischen Wissenschaftler und ihre emigrierten Kollegen, die am Bau der Atombombe beteiligt waren, verfügten über sehr widersprüchliche und großteils falsche Informationen über den Fortschritt des deutschen Uranprogramms. Noch nach Kriegsende lässt sich dies an Aussagen des Leiters der amerikanischen Alsos-Mission, Samuel Goudsmit, festmachen. Tatsächlich war das deutsche Programm hinsichtlich seiner wissenschaftlichen Grundlagen und des Managements nicht so unterlegen, wie vielfach behauptet wurde. Aber die deutschen Behörden waren nicht in der Lage, Geld und Ressourcen in gleichem Maße in das Uranprojekt zu investieren, wie etwa in das Peenemünder Raketenprojekt.

  16. The Deaf Acculturation Scale (DAS): Development and Validation of a 58-Item Measure

    PubMed Central

    Maxwell-McCaw, Deborah; Zea, Maria Cecilia

    2011-01-01

    This study involved the development and validation of the Deaf Acculturation Scale (DAS), a new measure of cultural identity for Deaf and hard-of-hearing (hh) populations. Data for this study were collected online and involved a nation-wide sample of 3,070 deaf/hh individuals. Results indicated strong internal reliabilities for all the subscales, and construct validity was established by demonstrating that the DAS could discriminate groups based on parental hearing status, school background, and use of self-labels. Construct validity was further demonstrated through factorial analyses, and findings resulted in a final 58-item measure. Directions for future research are discussed. PMID:21263041

  17. Psychometric properties of the Death Anxiety Scale (DAS) among terminally ill cancer patients.

    PubMed

    Royal, Kenneth D; Elahi, Fereshte

    2011-01-01

    Research conducted with the terminally ill population in relation to death anxiety is rare and mostly outdated. The purpose of this study was to evaluate the psychometric properties of the widely used Death Anxiety Scale (DAS) on a sample of terminal cancer patients.Additionally, validation studies of the DAS have exclusively used traditional statistical methods for analysis. The current study utilized an item response theory technique (IRT), namely the Rasch Rating Scale model for data analysis. The methodology employed may be useful for other researchers conducting validation studies from an IRT perspective.

  18. Anbindung des SISIS-SunRise-Bibliothekssystems an das zentrale Identitätsmanagement

    NASA Astrophysics Data System (ADS)

    Ebner, Ralf; Pretz, Edwin

    Wir berichten über Konzepte und Implementierungen zur Datenprovisionierung aus den Personenverwaltungssystemen der Technischen Universität München (TUM) über das zentrale Metadirectory am Leibniz-Rechenzentrum (LRZ) in das SISIS-SunRise-Bibliothekssystem der Universitätsbibliothek der TUM (TUB). Es werden drei Implementierungsvarianten diskutiert, angefangen von der Generierung und Übertragung einfacher CSV-Dateien über ein OpenLDAP-basiertes Konzept als Backend für die SISIS-Datenbank bis zur endgültigen Implementierung mit dem OCLC IDM Connector.

  19. The Deaf Acculturation Scale (DAS): development and validation of a 58-item measure.

    PubMed

    Maxwell-McCaw, Deborah; Zea, Maria Cecilia

    2011-01-01

    This study involved the development and validation of the Deaf Acculturation Scale (DAS), a new measure of cultural identity for Deaf and hard-of-hearing (hh) populations. Data for this study were collected online and involved a nation-wide sample of 3,070 deaf/hh individuals. Results indicated strong internal reliabilities for all the subscales, and construct validity was established by demonstrating that the DAS could discriminate groups based on parental hearing status, school background, and use of self-labels. Construct validity was further demonstrated through factorial analyses, and findings resulted in a final 58-item measure. Directions for future research are discussed.

  20. The Great War and Remembrance in Jose Leon Machado's "Memoria das Estrelas sem Brilho"

    ERIC Educational Resources Information Center

    Azevedo, Milton M.

    2011-01-01

    This article analyzes Jose Leon Machado's novel, "Memoria das Estrelas sem Brilho," as a multilayered historical novel in which a war story provides a background for comments on aspects of early twentieth-century Portuguese society, such as male bonding, religion, sexual mores, and social stratification. (Contains 11 notes.)

  1. Incorporating Parallel Computing into the Goddard Earth Observing System Data Assimilation System (GEOS DAS)

    NASA Technical Reports Server (NTRS)

    Larson, Jay W.

    1998-01-01

    Atmospheric data assimilation is a method of combining actual observations with model forecasts to produce a more accurate description of the earth system than the observations or forecast alone can provide. The output of data assimilation, sometimes called the analysis, are regular, gridded datasets of observed and unobserved variables. Analysis plays a key role in numerical weather prediction and is becoming increasingly important for climate research. These applications, and the need for timely validation of scientific enhancements to the data assimilation system pose computational demands that are best met by distributed parallel software. The mission of the NASA Data Assimilation Office (DAO) is to provide datasets for climate research and to support NASA satellite and aircraft missions. The system used to create these datasets is the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The core components of the the GEOS DAS are: the GEOS General Circulation Model (GCM), the Physical-space Statistical Analysis System (PSAS), the Observer, the on-line Quality Control (QC) system, the Coupler (which feeds analysis increments back to the GCM), and an I/O package for processing the large amounts of data the system produces (which will be described in another presentation in this session). The discussion will center on the following issues: the computational complexity for the whole GEOS DAS, assessment of the performance of the individual elements of GEOS DAS, and parallelization strategy for some of the components of the system.

  2. MiDAS: the field guide to the microbes of activated sludge

    PubMed Central

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes—knowledge that will be an invaluable resource for the optimal design and operation of these systems. Database URL: http://www.midasfieldguide.org PMID:26120139

  3. The Deaf Acculturation Scale (DAS): Development and Validation of a 58-Item Measure

    ERIC Educational Resources Information Center

    Maxwell-McCaw, Deborah; Zea, Maria Cecilia

    2011-01-01

    This study involved the development and validation of the Deaf Acculturation Scale (DAS), a new measure of cultural identity for Deaf and hard-of-hearing (hh) populations. Data for this study were collected online and involved a nation-wide sample of 3,070 deaf/hh individuals. Results indicated strong internal reliabilities for all the subscales,…

  4. A Brief History of the J.P. Das Developmental Disabilities Centre

    ERIC Educational Resources Information Center

    Sobsey, Dick

    2008-01-01

    The J.P. Das Developmental Disabilities Centre celebrated its 40th anniversary on September 1, 2007, followed by The University of Alberta's 100th anniversary in 2008. The year 2008 also brought the appointment of a new Director for the Centre. As the immediate past Director of the Centre, the author recounts some of the history of the J.P. Das…

  5. PoroTomo Project - Subatask 6.2: Deploy and Operate DAS and DTS arrays

    SciTech Connect

    Dante Fratta

    2016-03-31

    This metadata submission includes the coordinates of the DAS and DTS surface and borehole arrays, the list of file names, and the list of recorded files during testing at the PoroTomo Natural Laboratory at Brady Hot Spring in Nevada. Testing was completed during March 2016.

  6. MiDAS: the field guide to the microbes of activated sludge.

    PubMed

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes--knowledge that will be an invaluable resource for the optimal design and operation of these systems.

  7. Reisen im freien Fall - Teil 2: Das Zwillingsparadoxon aus dem Blickwinkel der ART

    NASA Astrophysics Data System (ADS)

    Sonne, Bernd; Weiß, Reinhard

    2013-07-01

    Nachdem wir uns mit den Prinzipien der ART und einigen Beispielen vertraut gemacht haben, kommen wir nun zur Berechnung des Zwillingsparadoxons aus Sicht des reisenden Zwillings. Dabei spielt das Äquivalenzprinzip eine große Rolle. Deshalb wird die Bewegungssituation noch einmal erläutert, diesmal aus Sicht von Katrin. Sie befindet sich in ihrem System S'in Ruhe. In ihrem System läuft die Zeit t'ab. Nach dem Start fühlt Katrin jedoch eine Kraft, die sie als Gravitationskraft interpretieren kann. Sie merkt es daran, dass sie in den Sitz gedrückt wird. Nach einiger Zeit werden die Triebwerke abgeschaltet, und das Raumschiff fliegt mit konstanter Geschwindigkeit weiter, Phase 2. Anschließend wird der Schub der Triebwerke solange umgekehrt, bis das Raumschiff irgendwo mit der Geschwindigkeit null am Umkehrpunkt U landet, Phase 3 (Abb. 15.1). Die Erde, auf der sich Michael befindet, bewegt sich mit x'(t') aus Sicht von Katrin im freien Fall von ihr weg, s. das Experiment mit dem steigenden Fahrstuhl in Abschn. 13.2.1.

  8. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  9. A Letter to the Parent(s) of a Child with Developmental Apraxia of Speech. Part IV: Treatment of DAS.

    ERIC Educational Resources Information Center

    Hall, Penelope K.

    2000-01-01

    One of a series of letters to parents of children with developmental apraxia of speech (DAS), this letter discusses the treatment of DAS including linguistic approaches, motor-programming approaches, a combination of linguistic and motor-programming approaches, and treatment approaches that include specific sensory and gestural cueing techniques.…

  10. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... catch limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ... limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ). (a... limited access scallop fishery shall be allocated 94.5 percent of the ACL specified in paragraph (a)(1)...

  11. DAS Boot!

    ERIC Educational Resources Information Center

    Chretien, Wendy

    2007-01-01

    The residential services group is lobbying to dump its aging hard-wired phone system because students don't use it. The town and campus public safety officials are demanding that their portable two-way radios operate well not only outdoors, but within campus buildings. Students are now expecting text messaging and WiFi service to work everywhere…

  12. Clinical potential of DAS181 for treatment of parainfluenza-3 infections in transplant recipients.

    PubMed

    Guzmán-Suarez, B B; Buckley, M W; Gilmore, E T; Vocca, E; Moss, R; Marty, F M; Sanders, R; Baden, L R; Wurtman, D; Issa, N C; Fang, F; Koo, S

    2012-08-01

    Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV-3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5-day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment.

  13. Annotation and visualization of endogenous retroviral sequences using the Distributed Annotation System (DAS) and eBioX

    PubMed Central

    Martínez Barrio, Álvaro; Lagercrantz, Erik; Sperber, Göran O; Blomberg, Jonas; Bongcam-Rudloff, Erik

    2009-01-01

    Background The Distributed Annotation System (DAS) is a widely used network protocol for sharing biological information. The distributed aspects of the protocol enable the use of various reference and annotation servers for connecting biological sequence data to pertinent annotations in order to depict an integrated view of the data for the final user. Results An annotation server has been devised to provide information about the endogenous retroviruses detected and annotated by a specialized in silico tool called RetroTector. We describe the procedure to implement the DAS 1.5 protocol commands necessary for constructing the DAS annotation server. We use our server to exemplify those steps. Data distribution is kept separated from visualization which is carried out by eBioX, an easy to use open source program incorporating multiple bioinformatics utilities. Some well characterized endogenous retroviruses are shown in two different DAS clients. A rapid analysis of areas free from retroviral insertions could be facilitated by our annotations. Conclusion The DAS protocol has shown to be advantageous in the distribution of endogenous retrovirus data. The distributed nature of the protocol is also found to aid in combining annotation and visualization along a genome in order to enhance the understanding of ERV contribution to its evolution. Reference and annotation servers are conjointly used by eBioX to provide visualization of ERV annotations as well as other data sources. Our DAS data source can be found in the central public DAS service repository, , or at . PMID:19534743

  14. 50 CFR 648.53 - Target total allowable catch, DAS allocations, and individual fishing quotas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... additional DAS in proportion to the unharvested possession limit. For example, if a full-time vessel had an... calculate meat-weight, up to a maximum of 400 lb (181.4 kg) per trip. (B) Years active. For each eligible....125 5 1.25 (D) Contribution factor example. If a vessel landed 48,550 lb (22,022 kg) of scallops...

  15. Assimilation of SBUV Version 8 Radiances into the GEOS Ozone DAS

    NASA Technical Reports Server (NTRS)

    Mueller, Martin D.; Stajner, Ivanka; Bhartia, Pawan K.

    2004-01-01

    In operational weather forecasting, the assimilation of brightness temperatures from satellite sounders, instead of assimilation of 1D-retrievals has become increasingly common practice over the last two decades. Compared to these systems, assimilation of trace gases is still at a relatively early stage of development, and efforts to directly assimilate radiances instead of retrieved products have just begun a few years ago, partially because it requires much more computation power due to the employment of a radiative transport forward model (FM). This paper will focus on a method to assimilate SBUV/2 radiances (albedos) into the Global Earth Observation System Ozone Data Assimilation Scheme (GEOS-03DAS). While SBUV-type instruments cannot compete with newer sensors in terms of spectral and horizontal resolution, they feature a continuous data record back to 1978, which makes them very valuable for trend studies. Assimilation can help spreading their ground coverage over the whole globe, as has been previously demonstrated with the GEOS-03DAS using SBUV Version 6 ozone profiles. Now, the DAS has been updated to use the newly released SBUV Version 8 data. We will compare pre]lmlnarv results of SBUV radiance assimilation with the assimilation of retrieved ozone profiles, discuss methods to deal with the increased computational load, and try to assess the error characteristics and future potential of the new approach.

  16. pH modulates arsenic toxicity in Bacillus licheniformis DAS-2.

    PubMed

    Tripti, K; Shardendu

    2016-08-01

    The toxic characteristics of arsenic species, As(V) and As(III) result in ecological risks. Arsenic tolerant bacterium was isolated and identified as the Bacillus licheniformis DAS-2 through 16SrDNA sequencing. B. licheniformis DAS-2 was efficient to tolerate and remove both the As(V)[MIC 8mM] and As(III)[MIC 6mM] from the growth medium. The potential for the removal/uptake of arsenic from the 3, 5 and 7mM As(V) enriched growth media was 100%, 60% and 35% respectively and from the 1, 3 and 5mM As(III) enrichment it was 100%, 99% and 58% respectively at neutral pH. 80% of uptake As(V) was reduced to As(III) in 3mM As(V) enrichment which was gradually decreased to only 17% at 7mM As(V) enrichment at neutral pH. The arsenic toxicity in B. licheniformis DAS-2 was found modulated by pH and was examined through alteration in growth, uptake/removal, reduction and measurement of chemical toxicity.

  17. I/O Parallelization for the Goddard Earth Observing System Data Assimilation System (GEOS DAS)

    NASA Technical Reports Server (NTRS)

    Lucchesi, R.; Sawyer, W.; Takacs, L. L.; Lyster, P.; Zero, J.

    1999-01-01

    The National Aeronautics and Space Administration (NASA) Data Assimilation Office (DAO) at the Goddard Space Flight Center (GSFC) has developed the GEOS DAS, a data assimilation system that provides production support for NASA missions and will support NASA's Earth Observing System (EOS) in the coming years. The DAO's support of the EOS project along with the requirement of producing long-term reanalysis datasets with an unvarying system levy a large I/O burden on the future system. The DAO has been involved in prototyping parallel implementations of the GEOS DAS for a number of years and is now converting the production version from shared-memory parallelism to distributed-memory parallelism using the portable Message-Passing Interface (MPI). If the MPI-based GEOS DAS is to meet these production requirements, we must make I/O from the parallel system efficient. We have designed a scheme that allows efficient I/O processing while retaining portability, reducing the need for post-processing, and producing data formats that are required by our users, both internal and external. The first phase of the GEOS DAS Parallel I/O System (GPIOS) will expand upon the common method of gathering global data to a Single PE for output. Instead of using a PE also tasked with primary computation, a number of PEs will be dedicated to I/O and its related tasks. This allows the data transformations and formatting required prior to output to take place asynchronously with respect to the GEOS DAS assimilation cycle, improving performance and generating output data sets in a format convenient for our users. I/O PEs can be added as needed to handle larger data volumes or to meet user file specifications. We will show I/O performance results from a prototype MPI GCM integrated with GPIOS. Phase two of GPIOS development will examine ways of integrating new software technologies to further improve performance and build scalability into the system. The maturing of MPI-IO implementations and

  18. Validation of Land-Surface Mosaic Heterogeneity in the GEOS DAS

    NASA Technical Reports Server (NTRS)

    Bosilovich, Michael G.; Molod, Andrea; Houser, Paul R.; Schubert, Siegfried

    1999-01-01

    The Mosaic Land-surface Model (LSM) has been included into the current GEOS Data Assimilation System (DAS). The LSM uses a more advanced representation of physical processes than previous versions of the GEOS DAS, including the representation of sub-grid heterogeneity of the land-surface through the Mosaic approach. As a first approximation, Mosaic assumes that all similar surface types within a grid-cell can be lumped together as a single'tile'. Within one GCM grid-cell, there might be 1 - 5 different tiles or surface types. All tiles are subjected to the grid-scale forcing (radiation, air temperature and specific humidity, and precipitation), and the sub-grid variability is a function of the tile characteristics. In this paper, we validate the LSM sub-grid scale variability (tiles) using a variety of surface observing stations from the Southern Great Plains (SGP) site of the Atmospheric Radiation Measurement (ARM) Program. One of the primary goals of SGP ARM is to study the variability of atmospheric radiation within a G,CM grid-cell. Enough surface data has been collected by ARM to extend this goal to sub-grid variability of the land-surface energy and water budgets. The time period of this study is the Summer of 1998 (June I - September 1). The ARM site data consists of surface meteorology, energy flux (eddy correlation and bowen ratio), soil water observations spread over an area similar to the size of a G-CM grid-cell. Various ARM stations are described as wheat and alfalfa crops, pasture and range land. The LSM tiles considered at the grid-space (2 x 2.5) nearest the ARM site include, grassland, deciduous forests, bare soil and dwarf trees. Surface energy and water balances for each tile type are compared with observations. Furthermore, we will discuss the land-surface sub-grid variability of both the ARM observations and the DAS.

  19. High resolution DAS via sinusoidal frequency scan OFDR (SFS-OFDR).

    PubMed

    Leviatan, Eyal; Eyal, Avishay

    2015-12-28

    There are many advantages to using direct frequency modulation for OFDR based DAS. However, achieving sufficiently linear scan via direct frequency modulation is challenging and poses limits on the scan parameters. A novel method for analyzing sinusoidal frequency modulated light is presented and demonstrated for both static and dynamic sensing. SFS-OFDR projects the measured signal onto appropriate sinusoidal phase terms to obtain spatial information. Thus, by using SFS-OFDR on sinusoidal modulated light it is possible to make use of the many advantages offered by direct frequency modulation without the limitations posed by the linearity requirement.

  20. [An example of partnership cooperation. Cantonal League against Tuberculosis and Lung Diseases/Association "Das Band"].

    PubMed

    Michaelis, E

    1984-01-01

    Together with the Cantonal League against Tuberculosis and Lung Diseases of Zurich, the Association "Das Band" has organized a first course for parents of children with asthma. The course is a component of the associations new "Prophylaxis Program for Children with Asthma and Their Parents". By exchanging ideas, the parents should become able to reflect their situation, characterized by excessive protectionism, aggressiveness, and guiltiness, and they also should learn to accept the disease as a part of their daily life. The first course, which meanwhile is followed by a second one, provided a first base for the solution of the many problems.

  1. The development of Music in Dementia Assessment Scales (MiDAS).

    PubMed

    McDermott, Orii; Orrell, Martin; Ridder, Hanne Mette

    2015-07-03

    There is a need to develop an outcome measure specific to music therapy in dementia that reflects a holistic picture of the therapy process and outcome. This study aimed to develop a clinically relevant and scientifically robust music therapy outcome measure incorporating the values and views of people with dementia. Focus groups and interviews were conducted to obtain qualitative data on what music meant to people with dementia and the observed effects of music. Expert and peer consultations were conducted at each stage of the measure development to maximise its content validity. The new measure was field-tested by clinicians in a care home. Feedback from the clinicians and music therapy experts were incorporated during the review and refinement process of the measure. A review of the existing literature, the experiential results and the consensus process enabled the development of the new outcome measure "Music in Dementia Assessment Scales (MiDAS)". Analysis of the qualitative data identified five key areas of the impact of music on people with dementia and they were transformed as the five Visual Analogue Scale (VAS) items: levels of Interest, Response, Initiation, Involvement and Enjoyment. MiDAS comprises the five VAS items and a supplementary checklist of notable positive and negative reactions from the individual. This study demonstrates that it is possible to design and develop an easy to apply and rigorous quantitative outcome measure which has a high level of clinical relevance for people with dementia, care home staff and music therapists.

  2. Ocean Color Measurements from Landsat-8 OLI using SeaDAS

    NASA Technical Reports Server (NTRS)

    Franz, Bryan Alden; Bailey, Sean W.; Kuring, Norman; Werdell, P. Jeremy

    2014-01-01

    The Operational Land Imager (OLI) is a multi-spectral radiometer hosted on the recently launched Landsat-8 satellite. OLI includes a suite of relatively narrow spectral bands at 30-meter spatial resolution in the visible to shortwave infrared that make it a potential tool for ocean color radiometry: measurement of the reflected spectral radiance upwelling from beneath the ocean surface that carries information on the biogeochemical constituents of the upper ocean euphotic zone. To evaluate the potential of OLI to measure ocean color, processing support was implemented in SeaDAS, which is an open-source software package distributed by NASA for processing, analysis, and display of ocean remote sensing measurements from a variety of satellite-based multi-spectral radiometers. Here we describe the implementation of OLI processing capabilities within SeaDAS, including support for various methods of atmospheric correction to remove the effects of atmospheric scattering and absorption and retrieve the spectral remote-sensing reflectance (Rrs; sr exp 1). The quality of the retrieved Rrs imagery will be assessed, as will the derived water column constituents such as the concentration of the phytoplankton pigment chlorophyll a.

  3. A causa das estações do ano: modelos mentais

    NASA Astrophysics Data System (ADS)

    de Campos, J. A. S.; de Araujo, J. F. S.

    2003-08-01

    A década de 70 do século passado foi marcada pelo estudo das concepções alternativas que os alunos trazem para a sala de aula. A identificação destas concepções foi o ponto de partida para promover a mudança conceitual, onde as pré-concepções seriam trocadas pelas concepções científicas. Na década seguinte, surgiram muitas propostas de estratégias educacionais para facilitar esta troca, na sua maioria baseadas na idéia do conflito cognitivo, proposta por Piaget. Entretanto, os resultados pouco animadores conduziram à percepção de que a mudança conceitual é um processo mais complexo. Pelas idéias da Ciência Cognitiva, a mudança conceitual é uma mudança progressiva dos modelos mentais que o aluno tem sobre o mundo físico, através de enriquecimento e revisão. A causa das Estações do Ano é um tópico sobre o qual a maioria dos estudantes apresenta concepções alternativas. Os autores fizeram um levantamento sobre as pré-concepções encontradas em trabalhos sobre o tema (16 referências), procurando encontrar elementos comuns que indicassem a presença de modelos mentais específicos. As pré-concepções encontradas na literatura foram obtidas usando-se diversas metodologias (desde entrevistas clínicas até questionários de múltipla escolha) e envolvendo alunos e professores de diferentes regiões geográficas. A partir de uma análise aprofundada de cada trabalho, e utilizando-se a técnica das Redes Sistêmicas, chegou-se a conclusão que as diversas pré-concepções identificadas (em torno de 50), poderiam ser representadas por 6 modelos mentais, onde a explicação da causa das estações do ano tem um mecanismo causal responsável. Os mecanismos causais identificados foram: a dependência da distância, a dependência da orientação, a dependência conjunta da distância e orientação, a dependência da obstrução, a dependência da velocidade e a dependência da inclinação dos raios solares. Foram ainda identificadas

  4. Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets.

    PubMed

    Świątek-Połatyńska, Magdalena A; Bucca, Giselda; Laing, Emma; Gubbens, Jacob; Titgemeyer, Fritz; Smith, Colin P; Rigali, Sébastien; van Wezel, Gilles P

    2015-01-01

    Streptomycetes produce a wealth of natural products, including over half of all known antibiotics. It was previously demonstrated that N-acetylglucosamine and secondary metabolism are closely entwined in streptomycetes. Here we show that DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR can bind to sites in the S. coelicolor genome that have no obvious resemblance to previously identified DasR-responsive elements. Thus, the regulon of DasR extends well beyond what was previously predicted and includes a large number of genes with functions far removed from N-acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases. Conversely, the DasR regulon during vegetative growth largely correlates to the presence of canonical DasR-responsive elements. The changes in DasR binding in vivo following N-acetylglucosamine induction were studied in detail and a possible molecular mechanism by which the influence of DasR is extended is discussed. Discussion of DasR binding was further informed by a parallel transcriptome analysis of the respective cultures. Evidence is provided that DasR binds directly to the promoters of all genes encoding pathway-specific regulators of antibiotic production in S. coelicolor, thereby providing an exquisitely simple link between nutritional control and secondary metabolism.

  5. Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene

    NASA Astrophysics Data System (ADS)

    Lee, Hyunah; Nam, Donggyu; Choi, Jae-Kyung; Araúzo-Bravo, Marcos J.; Kwon, Soon-Yong; Zaehres, Holm; Lee, Taehee; Park, Chan Young; Kang, Hyun-Wook; Schöler, Hans R.; Kim, Jeong Beom

    2016-02-01

    The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC.

  6. Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene

    PubMed Central

    Lee, Hyunah; Nam, Donggyu; Choi, Jae-Kyung; Araúzo-Bravo, Marcos J.; Kwon, Soon-Yong; Zaehres, Holm; Lee, Taehee; Park, Chan Young; Kang, Hyun-Wook; Schöler, Hans R.; Kim, Jeong Beom

    2016-01-01

    The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC. PMID:26846167

  7. Measuring Primary Teachers' Attitudes Toward Teaching Science: Development of the Dimensions of Attitude Toward Science (DAS) Instrument

    NASA Astrophysics Data System (ADS)

    van Aalderen-Smeets, Sandra; Walma van der Molen, Juliette

    2013-03-01

    In this article, we present a valid and reliable instrument which measures the attitude of in-service and pre-service primary teachers toward teaching science, called the Dimensions of Attitude Toward Science (DAS) Instrument. Attention to the attitudes of primary teachers toward teaching science is of fundamental importance to the professionalization of these teachers in the field of primary science education. With the development of this instrument, we sought to fulfill the need for a statistically and theoretically valid and reliable instrument to measure pre-service and in-service teachers' attitudes. The DAS Instrument is based on a comprehensive theoretical framework for attitude toward (teaching) science. After pilot testing, the DAS was revised and subsequently validated using a large group of respondents (pre-service and in-service primary teachers) (N = 556). The theoretical underpinning of the DAS combined with the statistical data indicate that the DAS possesses good construct validity and that it proves to be a promising instrument that can be utilized for research purposes, and also as a teacher training and coaching tool. This instrument can therefore make a valuable contribution to progress within the field of science education.

  8. Subchronic feeding study with genetically modified stacked trait lepidopteran and coleopteran resistant (DAS-Ø15Ø7-1xDAS-59122-7) maize grain in Sprague-Dawley rats.

    PubMed

    Appenzeller, Laura M; Malley, Linda; Mackenzie, Susan A; Hoban, Denise; Delaney, Bryan

    2009-07-01

    DAS-Ø15Ø7-1xDAS-59122-7 (1507x59122) is a genetically modified (GM) maize hybrid that was produced by crossing of two GM maize inbreds; DAS-Ø15Ø7-1 and DAS-59122-7. This hybrid cross expresses four transgenic proteins: Cry1F and PAT (from DAS-Ø15Ø7-1) and Cry34Ab1/Cry35Ab1 and PAT (from DAS-59122-7) that confer resistance to lepidopteran and coleopteran pests and tolerance to the herbicidal active ingredient glufosinate-ammonium. The current subchronic feeding study was conducted in Sprague-Dawley rats to evaluate the potential health effects of long-term consumption of a rodent diet containing 1507x59122 maize grain compared with a diet containing maize grain from its near-isogenic control (091). Diets formulated with three unrelated non-GM commercial hybrids (3573, 35P12, 36G12) were also included for within study reference data. All diets contained 34% (w/wt) maize grain and were prepared according to the specifications of PMI((R)) Nutrition International, LLC Certified Rodent LabDiet((R)) 5002 (PMI((R)) 5002). Diets were fed ad libitum to rats for at least 92days. OECD 408 response variables from rats fed the 1507x59122 diet were compared with those from rats fed the 091 control diet. No toxicologically significant differences were observed in nutritional performance variables, clinical and neurobehavioral signs, ophthalmology, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), organ weights, and gross and microscopic pathology between rats in the 091 and 1507x59122 treatment groups. The results from this study demonstrate that 1507x59122 maize grain is as safe and nutritious as non-GM maize grain and support the concept that crossing of two safe GM maize events results in production of a safe stacked GM event.

  9. Análise da cinemática interna das regiões HII gigantes e das galáxias HII

    NASA Astrophysics Data System (ADS)

    Plana, H.; Telles, E.; Maíz-Apellániz, J.

    2003-08-01

    Neste trabalho nós mostramos os primeiros resultados de um estudo sobre a cinemática das Regiões HII Gigantes (GHIIRs) em galáxias próximas. Essas regiões HII têm um diâmetro médio entre 100 pc e 1000 pc e uma taxa de formação estelar de 106 M¤ / ano sendo equivalente à observada em galáxias de tipo tardio correspondendo a uma taxa de formação estelar por unidade de volume uma ordem de magnitude maior que a observada em regiões HII normais. Usando espectros de fenda longas em várias posições, nós construímos mapas de velocidades, de dispersão e de intensidade para várias linhas de emissão como Ha, Hb, [NII]6584 Å, [OIII]5007 Å e o doublet de [SII], para cinco regiões gigantes: NGC 2403 II e IV, NGC 595, NGC 5461, NGC 5471, NGC 5455. O estudo da cinemática (mapas de velocidades e da dispersão) mostrou, por exemplo, a presença de cascas em expansão em NGC 595 ou perfis de emissão com várias componentes em NGC 5461. Os perfis de emissão também mostram velocidades supersônicas. Os resultados são discutidos em comparação com os de estudos anteriores realizados.

  10. DasPy – Open Source Multivariate Land Data Assimilation Framework with High Performance Computing

    NASA Astrophysics Data System (ADS)

    Han, Xujun; Li, Xin; Montzka, Carsten; Kollet, Stefan; Vereecken, Harry; Hendricks Franssen, Harrie-Jan

    2015-04-01

    Data assimilation has become a popular method to integrate observations from multiple sources with land surface models to improve predictions of the water and energy cycles of the soil-vegetation-atmosphere continuum. In recent years, several land data assimilation systems have been developed in different research agencies. Because of the software availability or adaptability, these systems are not easy to apply for the purpose of multivariate land data assimilation research. Multivariate data assimilation refers to the simultaneous assimilation of observation data for multiple model state variables into a simulation model. Our main motivation was to develop an open source multivariate land data assimilation framework (DasPy) which is implemented using the Python script language mixed with C++ and Fortran language. This system has been evaluated in several soil moisture, L-band brightness temperature and land surface temperature assimilation studies. The implementation allows also parameter estimation (soil properties and/or leaf area index) on the basis of the joint state and parameter estimation approach. LETKF (Local Ensemble Transform Kalman Filter) is implemented as the main data assimilation algorithm, and uncertainties in the data assimilation can be represented by perturbed atmospheric forcings, perturbed soil and vegetation properties and model initial conditions. The CLM4.5 (Community Land Model) was integrated as the model operator. The CMEM (Community Microwave Emission Modelling Platform), COSMIC (COsmic-ray Soil Moisture Interaction Code) and the two source formulation were integrated as observation operators for assimilation of L-band passive microwave, cosmic-ray soil moisture probe and land surface temperature measurements, respectively. DasPy is parallelized using the hybrid MPI (Message Passing Interface) and OpenMP (Open Multi-Processing) techniques. All the input and output data flow is organized efficiently using the commonly used NetCDF file

  11. Viscous dissipation effects on unsteady mixed convective stagnation point flow using Tiwari-Das nanofluid model

    NASA Astrophysics Data System (ADS)

    Mabood, F.; Ibrahim, S. M.; Kumar, P. V.; Khan, W. A.

    A mathematical model has been developed using Tiwari-Das model to study the MHD stagnation-point flow and heat transfer characteristics of an electrically conducting nanofluid over a vertical permeable shrinking/stretching sheet in the presence of viscous dissipation. Formulated partial differential equations are converted into a set of ordinary differential equations using suitable similarity transformation. Runge-Kutta-Fehlberg method with shooting technique is applied to solve the resulting coupled ordinary differential equations. The profiles for velocity, temperature, skin friction coefficient and local Nusselt number for various parameters are displayed through graphs and tabular forms. In this problem, we considered two types of nanoparticles, namely, copper (Cu) and Alumina (Al2O3) with water as base fluid.

  12. Sobre o uso das séries de Puiseux em mecanica celeste

    NASA Astrophysics Data System (ADS)

    Miloni, O. I.

    2003-08-01

    Neste trabalho é apresentada uma demonstração do uso dos diferentes desenvolvimentos em séries para as equações de perturbação em Mecânica Celeste no marco Hamiltoniano. Em trabalhos clássicos como os de Poincaré (Poincaré, 1893) por exemplo, já esta planteado o uso de potências não inteiras no pequeno parâmetro, o que evidencia a não analiticidade das funções quando uma ressonância ocorre. Nestes trabalhos os desenvolvimentos são na raíz quadrada da massa de Júpiter (o pequeno parâmetro). Mais recentemente (Ferraz-Mello, 1985) outros tipos de desenvolvimentos foram aplicados modificando substancialmente as ordens de grandeza e a velocidade de convergência das séries. Com esta abordagem, os desenvolvimentos foram expressados em termos da raíz cúbica do pequeno parâmetro. Neste trabalho apresentamos um enfoque geral, onde os diferentes tipos de desenvolvimentos em séries de Puiseux (Valiron, 1950) são obtidos a partir da aplicação de Teorema de Preparação de Weierstrass (Goursat, 1916) considerando a equação de Hamilton-Jacobi como uma equação algébrica. Os resultados são aplicados ao problema restrito dos três corpos em ressonância de primeira ordem e, dependendo da grandeza da excentricidade do asteróide em relação à de Júpiter, obtemos os diferentes desenvolvimentos, em raíz quadrada ou raíz cúbica da massa de Júpiter.

  13. Event DAS-444Ø6-6 soybean grown in Brazil is compositionally equivalent to non-transgenic soybean.

    PubMed

    Fast, Brandon J; Galan, Maria P; Schafer, Ariane C

    2016-04-02

    Soybean event DAS-444Ø6-6 is tolerant to the herbicides 2,4-D, glyphosate, and glufosinate. An investigation of potential unintended adverse compositional changes in a genetically modified crop is required to meet government regulatory requirements in various geographies. A study to meet these requirements in Brazil was completed demonstrating compositional equivalency between DAS-444Ø6-6 and non-transgenic soybean. This study supplements the extensive literature supporting transgenesis as less disruptive of crop composition compared with traditional breeding methods.

  14. Latent Factor Structure of the Das-Naglieri Cognitive Assessment System: A Confirmatory Factor Analysis in a Chinese Setting

    ERIC Educational Resources Information Center

    Deng, Ci-ping; Liu, Ming; Wei, Wei; Chan, Raymond C. K.; Das, J. P.

    2011-01-01

    This study aims to measure the psychometric properties of the Das-Naglieri Cognitive Assessment System (D-N CAS) and to determine its clinical utility in a Chinese context. Confirmatory factor analysis (CFA) was conducted to examine the construct validity of the Chinese version of the D-N CAS among a group of 567, normally developed children.…

  15. Concurrent Validity of the WISC-IV and DAS-II in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Kuriakose, Sarah

    2014-01-01

    Cognitive assessments are used for a variety of research and clinical purposes in children with autism spectrum disorder (ASD). This study establishes concurrent validity of the Wechsler Intelligence Scales for Children-fourth edition (WISC-IV) and Differential Ability Scales-second edition (DAS-II) in a sample of children with ASD with a broad…

  16. Measuring Primary Teachers' Attitudes toward Teaching Science: Development of the Dimensions of Attitude toward Science (DAS) Instrument

    ERIC Educational Resources Information Center

    van Aalderen-Smeets, Sandra; Walma van der Molen, Juliette

    2013-01-01

    In this article, we present a valid and reliable instrument which measures the attitude of in-service and pre-service primary teachers toward teaching science, called the Dimensions of Attitude Toward Science (DAS) Instrument. Attention to the attitudes of primary teachers toward teaching science is of fundamental importance to the…

  17. Planning Ability across Ranges of Intellectual Ability: An Examination of the Luria-Das Information-Processing Model.

    ERIC Educational Resources Information Center

    McCallum, R. Steve; And Others

    1988-01-01

    Based on Luria-Das information processing theory, hypothesized that 26 educable mentally retarded children would score significantly less well on relatively pure measures of planning ability than would 13 younger average ability students after students were matched on cognitive processing ability. Hypothesis was not supported by study. (Author/NB)

  18. Test Review: Naglieri, J. A., Das, J. P., & Goldstein, S. (2014). Cognitive Assessment System-Second Edition (2nd Ed.)

    ERIC Educational Resources Information Center

    McGill, Ryan J.

    2015-01-01

    The Cognitive Assessment System-Second Edition (CAS2) is an individually administered measure of cognitive ability designed for children and adolescents ages 5 through 18 years. The measure, authored by Jack A. Naglieri, J. P. Das, and Sam Goldstein, was published by Pro-Ed in 2014 and is the first revision of the Cognitive Assessment System (CAS;…

  19. Impaired Left Ventricular Diastolic Functions and Thickened Epicardial Adipose Tissue in Rheumatoid Arthritis Patients is Correlated with DAS-28 Score

    PubMed Central

    Alpaydın, Sertac; Buyukterzi, Zafer; Akkurt, Halil Ekrem; Yılmaz, Halim

    2017-01-01

    Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that is known to be associated with high cardiovascular (CV) morbidity and mortality. In this study, we aimed to demonstrate whether RA disease activity reflected with disease activity score-28 (DAS-28) had an impact on left ventricular diastolic functions and epicardial adipose tissue (EAT) thickness in RA patients with no traditional CV risk factors. Methods In this retrospective study, 41 patients newly diagnosed with RA were included. In addition to medical history, detailed physical examination findings and laboratory tests, left ventricular systolic and diastolic functions, chamber dimensions, and EAT thickness were evaluated with transthoracic echocardiography in the study population. Results This study included 41 subjects with a median age of 45 years (38.00-55.50), of which 29.27% were male. In the binomial logistic regression analysis, DAS-28 score was found to be an independent associate of diastolic dysfunction, Additionally, DAS-28 was found to be independently associated with EAT thickness. Conclusions Patients with high DAS-28 score should be evaluated thoroughly for CV disease, and patients should undergo advanced diagnostic studies as required and receive appropriate treatment. PMID:28344422

  20. Design study for Thermal Infrared Multispectral Scanner (TIMS)

    NASA Technical Reports Server (NTRS)

    Stanich, C. G.; Osterwisch, F. G.; Szeles, D. M.; Houtman, W. H.

    1981-01-01

    The feasibility of dividing the 8-12 micrometer thermal infrared wavelength region into six spectral bands by an airborne line scanner system was investigated. By combining an existing scanner design with a 6 band spectrometer, a system for the remote sensing of Earth resources was developed. The elements in the spectrometer include an off axis reflective collimator, a reflective diffraction grating, a triplet germanium imaging lens, a photoconductive mercury cadmium telluride sensor array, and the mechanical assembly to hold these parts and maintain their optical alignment across a broad temperature range. The existing scanner design was modified to accept the new spectrometer and two field filling thermal reference sources.

  1. iLIDS Simulations and Videos for Docking TIM

    NASA Technical Reports Server (NTRS)

    Lewis, James L.

    2010-01-01

    The video shows various aspects of the International Low Impact Docking System, including team members, some production, configuration, mated androgynous iLIDS, SCS Lockdown system, thermal analysis, electrical engineering aspects, the iLIDS control box and emulator, radiation testing at BNL, component environmental testing, component vibration testing, 3G processor board delivery system, GTA vibe test, EMA testbed, hook and hook disassembly, flex shaftdrive assembly, GSE cradle MISSE-6 Columbus, MISSE 6 and 7 seal experiments, actuated full scale seal test rig, LIDS on Hubble, dynamics test prep, EDU 54 mass emulation and SCS, load ring characterization, 6DOF proof test, SCS at 6DOF, machining EEMS and inner ring assembly, APAS assembly, inner ring fitting, rotation stand assembly, EEMS mating, and EEMS proof of concept demonstration.

  2. Using the TIMS to estimate evapotranspiration from a forest

    NASA Technical Reports Server (NTRS)

    Teskey, Robert

    1991-01-01

    The main goals were: (1) to characterize the evapotranspiration (Et) of two forested watersheds using direct measurement techniques, and (2) to evaluate if remotely sensed surface temperatures could be used to estimate Et from the same watersheds. Two independent approaches for estimating the Et from watersheds were used. The first was derived using the Penman-Monteith Equation. This model requires the direct measurement of the microclimate of the site as well as biological measurements, i.e., stomatal conductance to water vapor and the leaf area of the stand. The primary limitation of this approach is that the measurement of stomatal conductance is time consuming, and in large trees, access to the foliage is difficult so the sample must be limited to the small number of trees. In the study, the sample was limited to the trees which could be measured from a single tower in each stand.

  3. The Independent School Admissions Director as Tim Wakefield's Catcher

    ERIC Educational Resources Information Center

    Vachow, Mike

    2012-01-01

    Bob Uecker, the Milwaukee Brewers' quipping radio broadcaster, makes his brief and lackluster career as a major league catcher the subject of much of his humor. About catching the knuckleball, Uecker famously said, "I always thought the knuckleball was the easiest pitch to catch." Of course, there is an even better way to catch a knuckleball, and…

  4. Targeting Tim-1 to Circumvent Immune Tolerance in Prostate Cancer

    DTIC Science & Technology

    2012-09-01

    Blumenstein, L. M. Glode, D. L. Bilhartz, M. Wyand, K. Manson , D. L. Panicali, R. Laus, J. Schlom, W. L. Dahut, P. M. Arlen, J. L. Gulley, and W. R...2122– 2132. [PubMed: 15169798] 12. Sanda MG, Smith DC, Charles LG, Hwang C, Pienta KJ, Schlom J, Milenic D, Panicali D, Montie JE. Recombinant...immunization. Prostate. 2009 15. Eng MH, Charles LG, Ross BD, Chrisp CE, Pienta KJ, Greenberg NM, Hsu CX, Sanda MG. Early castration reduces prostatic

  5. GOES-R with Dr. Kathy Sullivan and Tim Samaras

    NASA Video Gallery

    This short video features highlights from a live Nationwide broadcast that took place on April 3, 2012, from the studio of NASA Goddard TV. NOAA’s Deputy Administrator and Chief Scientist Dr. Ka...

  6. Tim Wirth: playing a leading role. Newsmaker interview.

    PubMed

    Pickett, S

    1995-01-01

    An interview with Timothy Wirth, who has been Under Secretary of State for Global Affairs, is presented. The US played a new role as a partner at several recent UN conferences that focused on a multiplicity of issues that harbinger the 21st century. The 4th World Conference on Women in Beijing in September 1995 underscored the importance of women as agents of change, confirmed the importance of nongovernmental organizations in affecting global change in governance, and revealed the strength of women's groups in developing countries. The US made some pledges at the 1994 UN Population and Development Conference in Cairo as laid down in the program of action. US financial commitment to population stabilization increased as did the commitment from Japan and other developed countries. Egypt, Indonesia, Tunisia, and Mexico with effective family planning programs are also sharing their experiences with other developing countries. The US has an interest in investing in foreign assistance in view of runaway population growth in countries like Haiti. Haiti's excess population would be heading for Florida. The President's Council on Sustainable Development's task force on population and consumption concluded that the US should commit itself to population stabilization because of the high consumption rate of the average American, the number of unplanned and unwanted pregnancies, and the problem of teenage pregnancies. Consumption rather than investment should taxed, subsidies should be removed from the use of natural resources and agriculture, and environmental degradation should be priced properly. Poverty is at the root of economic deprivation and environmental destruction. Micro-enterprises have been successful in Asia, Africa, and Latin America, which experiences could be used by the US as well. The broader empowerment of women could also encourage political change, which, in turn could bring about full access to family planning and support to women and their families.

  7. Stable Isotope Characterization of TICs/TIMs: Analytical Progress Report

    SciTech Connect

    Volpe, A M; Singleton, M J

    2009-06-05

    We measured twelve alkali cyanide samples that were also sent to ORNL and PNNL collaborators. While results indicate distinct {delta}{sup 13}C and {delta}{sup 15}N values that would be useful to signature studies, the alkali cyanides, especially NaCN, show chemical breakdown during storage that will influence forensic analysis. Carbon and nitrogen stable isotopic compositions of raw materials used to synthesis TETS were measured. Results indicate wide ranges in {delta}{sup 13}C and {delta}{sup 15}N values. Using these raw materials, LLNL scientists synthesized three batches of TETS following published procedures. Stable isotopic measurements of TETS synthesis products indicates nitrogen ({var_epsilon} {sup 15}N = -1.7 to -0.8) and carbon ({var_epsilon} {sup 13}C = -1.0 to -0.1) fractionation during production.

  8. Phase Velocity and Full-Waveform Analysis of Co-located Distributed Acoustic Sensing (DAS) Channels and Geophone Sensor

    NASA Astrophysics Data System (ADS)

    Parker, L.; Mellors, R. J.; Thurber, C. H.; Wang, H. F.; Zeng, X.

    2015-12-01

    A 762-meter Distributed Acoustic Sensing (DAS) array with a channel spacing of one meter was deployed at the Garner Valley Downhole Array in Southern California. The array was approximately rectangular with dimensions of 180 meters by 80 meters. The array also included two subdiagonals within the rectangle along which three-component geophones were co-located. Several active sources were deployed, including a 45-kN, swept-frequency, shear-mass shaker, which produced strong Rayleigh waves across the array. Both DAS and geophone traces were filtered in 2-Hz steps between 4 and 20 Hz to obtain phase velocities as a function of frequency from fitting the moveout of travel times over distances of 35 meters or longer. As an alternative to this traditional means of finding phase velocity, it is theoretically possible to find the Rayleigh-wave phase velocity at each point of co-location as the ratio of DAS and geophone responses, because DAS is sensitive to ground strain and geophones are sensitive to ground velocity, after suitable corrections for instrument response (Mikumo & Aki, 1964). The concept was tested in WPP, a seismic wave propagation program, by first validating and then using a 3D synthetic, full-waveform seismic model to simulate the effect of increased levels of noise and uncertainty as data go from ideal to more realistic. The results obtained from this study provide a better understanding of the DAS response and its potential for being combined with traditional seismometers for obtaining phase velocity at a single location. This analysis is part of the PoroTomo project (Poroelastic Tomography by Adjoint Inverse Modeling of Data from Seismology, Geodesy, and Hydrology, http://geoscience.wisc.edu/feigl/porotomo).

  9. DAS181 for Treatment of Parainfluenza Virus Infections in Hematopoietic Stem Cell Transplant Recipients at a Single Center.

    PubMed

    Salvatore, Mirella; Satlin, Michael J; Jacobs, Samantha E; Jenkins, Stephen G; Schuetz, Audrey N; Moss, Ronald B; Van Besien, Koen; Shore, Tsiporah; Soave, Rosemary

    2016-05-01

    Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy.

  10. (Re)locating (I)dentity With(in) Politicized (Re)presentation of Fe/Male Body in Kamala Das' Poetry

    ERIC Educational Resources Information Center

    Sultana, Sharmin; Sarwar, Nadia

    2016-01-01

    This paper is going to argue that the selected poems of renowned Indian poet Kamala Das are inclined to relocate both feminine and masculine identity through the politicized representation of body. Kamala Das' representation of body in her poems has always been viewed as a medium of re-historicizing the pain, sufferings, and psychological trauma…

  11. Common Data Acquisition Systems (DAS) Software Development for Rocket Propulsion Test (RPT) Test Facilities

    NASA Technical Reports Server (NTRS)

    Hebert, Phillip W., Sr.; Davis, Dawn M.; Turowski, Mark P.; Holladay, Wendy T.; Hughes, Mark S.

    2012-01-01

    The advent of the commercial space launch industry and NASA's more recent resumption of operation of Stennis Space Center's large test facilities after thirty years of contractor control resulted in a need for a non-proprietary data acquisition systems (DAS) software to support government and commercial testing. The software is designed for modularity and adaptability to minimize the software development effort for current and future data systems. An additional benefit of the software's architecture is its ability to easily migrate to other testing facilities thus providing future commonality across Stennis. Adapting the software to other Rocket Propulsion Test (RPT) Centers such as MSFC, White Sands, and Plumbrook Station would provide additional commonality and help reduce testing costs for NASA. Ultimately, the software provides the government with unlimited rights and guarantees privacy of data to commercial entities. The project engaged all RPT Centers and NASA's Independent Verification & Validation facility to enhance product quality. The design consists of a translation layer which provides the transparency of the software application layers to underlying hardware regardless of test facility location and a flexible and easily accessible database. This presentation addresses system technical design, issues encountered, and the status of Stennis development and deployment.

  12. Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors

    PubMed Central

    Fillenberg, Simon B.; Friess, Mario D.; Körner, Samuel; Böckmann, Rainer A.; Muller, Yves A.

    2016-01-01

    Small molecule effectors regulate gene transcription in bacteria by altering the DNA-binding affinities of specific repressor proteins. Although the GntR proteins represent a large family of bacterial repressors, only little is known about the allosteric mechanism that enables their function. DasR from Streptomyces coelicolor belongs to the GntR/HutC subfamily and specifically recognises operators termed DasR-responsive elements (dre-sites). Its DNA-binding properties are modulated by phosphorylated sugars. Here, we present several crystal structures of DasR, namely of dimeric full-length DasR in the absence of any effector and of only the effector-binding domain (EBD) of DasR without effector or in complex with glucosamine-6-phosphate (GlcN-6-P) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Together with molecular dynamics (MD) simulations and a comparison with other GntR/HutC family members these data allowed for a structural characterisation of the different functional states of DasR. Allostery in DasR and possibly in many other GntR/HutC family members is best described by a conformational selection model. In ligand-free DasR, an increased flexibility in the EBDs enables the attached DNA-binding domains (DBD) to sample a variety of different orientations and among these also a DNA-binding competent conformation. Effector binding to the EBDs of DasR significantly reorganises the atomic structure of the latter. However, rather than locking the orientation of the DBDs, the effector-induced formation of β-strand β* in the DBD-EBD-linker segment merely appears to take the DBDs ‘on a shorter leash’ thereby impeding the ‘downwards’ positioning of the DBDs that is necessary for a concerted binding of two DBDs of DasR to operator DNA. PMID:27337024

  13. The Trigger and Data Acquisition System (TriDAS) of the KM3NeT experiment

    NASA Astrophysics Data System (ADS)

    Pellegrino, C.; KM3NeT Collaboration

    2016-01-01

    Starting from 2015, the new generation underwater high energy neutrino telescope, KM3NeT, is being installed in the Mediterranean Sea. During Phase 1, 32 Detection Units (8 tower-like and 24 string-like) will be deployed in the Ionian Sea, about 100km offshore Portopalo di Capo Passero, Sicily, and 7 string-like DUs will be deployed in the MEUST site, offshore Toulon in France. During Phase 2, several hundreds of DUs will be added to the Phase 1 detector, reaching an effective detection volume of some cubic kilometres. In this contribution the Trigger and Data Acquisition System (TriDAS) of the string-based detector is described. The TriDAS is designed to scale with the detector size, allowing the read-out and the on-line trigger of data from both Phase 1 and Phase 2, whose continuous throughputs are expected to be about 10Gbps and more than 250Gbps, respectively.

  14. MoSST DAS: The First Working Geomagnetic Data Assimilation System

    NASA Technical Reports Server (NTRS)

    Kuang, Weijia; Wei, Zigang; Tangborn, Andrew

    2011-01-01

    The Earth possesses an internal magnetic field (geomagnetic field) generated by convection in the outer core (geodynamo). Previous efforts have been focused along two distinct paths: (1) numerical geodynamo modeling to understand the origin of the geomagnetic field, and the mechanisms of geomagnetic secular variations (SV); and (2) geomagnetic field modeling to map the spatial/temporal variations of the field from geomagnetic data, and to derive core properties, e.g. inversion of core flow near the core-mantle boundary (CMB). Geomagnetic data assimilation is a new approach emerged over the past 5 years: surface observations are assimilated with geodynamo models for better understanding of the core dynamical state, and accurately prediction of SV. In collaboration with several geomagnetic research groups, we have developed the first working geomagnetic data assimilation system, Modular, Scalable, Self-consistent, and Three-dimensional (MoSST) DAS, that includes the MoSST numerical dynamo model; 7000 years of geomagnetic field maps from several field models utilizing satellite and ground observatory data, historical magnetic records and archeo/paleo magnetic data; and an ensemble based optimal interpolation (01) assimilation algorithm. With this system, we have demonstrated clearly that the assimilated core dynamical state is substantially different from those of pure geodynamo simulations. Ensemble assimilation runs also show the convergence of the assimilated solutions inside the core, suggesting that the simulation state is pulled closer to the truth via data assimilation. The forecasts from this system are also very accurate: the 5-year forecast of the geomagnetic field agrees very well with the observations; and the 5-year secular variation forecast is more accurate than the IGRF SV forecast models in the past. Using geomagnetic records up to 2009, we have made an SV forecast for the period from 2010-2015, and is a candidate SV model for IGRF-11.

  15. Sensitivity of Global Modeling Initiative CTM predictions of Antarctic ozone recovery to GCM and DAS generated meteorological fields

    SciTech Connect

    Rotman, D; Bergmann, D

    2003-12-04

    We use the Global Modeling Initiative chemistry and transport model to simulate the evolution of stratospheric ozone between 1995 and 2030, using boundary conditions consistent with the recent World Meteorological Organization ozone assessment. We compare the Antarctic ozone recovery predictions of two simulations, one driven by meteorological data from a general circulation model (GCM), the other using the output of a data assimilation system (DAS), to examine the sensitivity of Antarctic ozone recovery predictions to the characteristic dynamical differences between GCM and DAS-generated meteorological data. Although the age of air in the Antarctic lower stratosphere differs by a factor of 2 between the simulations, we find little sensitivity of the 1995-2030 Antarctic ozone recovery between 350 K and 650 K to the differing meteorological fields, particularly when the recovery is specified in mixing ratio units. Relative changes are smaller in the DAS-driven simulation compared to the GCM-driven simulation due to a surplus of Antarctic ozone in the DAS-driven simulation which is not consistent with observations. The peak ozone change between 1995 and 2030 in both simulations is {approx}20% lower than photochemical expectations, indicating that changes in ozone transport at 450 K between 1995 and 2030 constitute a small negative feedback. Total winter/spring ozone loss during the base year (1995) of both simulations and the rate of ozone loss during August and September is somewhat weaker than observed. This appears to be due to underestimates of Antarctic Cl{sub y} at the 450 K potential temperature level.

  16. Predictors of European League Against Rheumatism (EULAR) good response, DAS-28 remission and sustained responses to TNF-inhibitors in rheumatoid arthritis: a prospective study in refractory disease.

    PubMed

    Mohammed, Reem Hamdy A; Farahat, Faisal; Kewan, Hanady H; Bukhari, Mohammed A

    2015-01-01

    The aim of this study was to survey factors related to EULAR good response, the DAS-28 definition of remission, ACR 50 response, sustained response to tumor necrosis factor inhibitors (TNF-I) therapy in biologic naïve patients with refractory rheumatoid arthritis. This was a single center observational clinical prospective 2 years' study, EULAR response criteria, DAS 28, HAQ and radiographic changes were recorded. Eighty patients included (64 females and 16 males, mean age was 48.4 + -17.9 years, mean disease duration 7.3 + -5.9 years). At 6 months 70% achieved EULAR good response, 51.8% achieved DAS-28 remission. Good response/sustained responses inversely correlated with baseline DAS-28 and radiographic erosions P <0.05. EULAR good response/remission by 6 months, sustained response at 2 years positively correlated with the decline in RF titers (r = 0.33, P < 0.05 & r = 0.30, P < 0.03 respectively), negatively correlated with the baseline HAQ. Regression analysis identified higher serum hemoglobin concentration, lower baseline HAQ scores, and the absence of radiographic erosions as significant predictors of good as well as sustained responses after adjustment for potential covariates. Methotrexate was associated with favorable responses and remission at 6 months (ORs = 1.13, 1.30 respectively). The study concluded that a lower baseline DAS-28 and HAQ scores, the lack of radiographic erosions favored EULAR good response and were significant predictors of sustained response to TNF-I.

  17. Properties of Noise Cross Correlation Functions Obtained from a Distributed Acoustic Sensing (DAS) Array at Garner Valley, California

    NASA Astrophysics Data System (ADS)

    Zeng, X.; Lancelle, C.; Thurber, C. H.; Fratta, D.; Wang, H. F.; Chalari, A.; Clarke, A.

    2015-12-01

    The field test of Distributed Acoustic Sensing (DAS) conducted at Garner Valley, California on September 11-12, 2013 provided a continuous overnight record of ambient noise. The DAS array recorded ground motions every one meter of optical cable that was arranged approximately in the shape of a rectangle with dimensions of 160 m by 80 m. The long dimension of the array was adjacent to a state highway. Three hours of record were used to compute noise cross-correlation functions (NCFs) in one-minute windows. The trace from each sensor channel was pre-processed by downsampling to 200 Hz, followed by normalization in the time-domain and bandpass filtering between 2 and 20 Hz (Bensen et al., 2007). The one-minute NCFs were then stacked using the time-frequency domain phase-weighted stacking method (Schimmel & Gallart, 2007). The NCFs between channels were asymmetrical reflecting the direction of traffic noise. The group velocities were found using the frequency-time analysis method. The energy was concentrated between 5 and 15 Hz, which falls into the typical traffic noise frequency band. The resulting velocities were between 100 and 300 m/s for frequencies between 10 and 20 Hz, which are in the same range as described in the results for surface-wave dispersion obtained using an active source for the same site (Lancelle et al., 2015). The group velocity starts to decrease for frequencies greater than ~10 Hz, which was expected on the basis of a previous shear-wave velocity model (Steidl et al., 1996). Then, the phase velocity was calculated using the multichannel analysis of surface wave technique (MASW - Park et al., 1999) with 114 NCFs spaced one meter apart. The resulting dispersion curve between 5 and 15 Hz gave phase velocities that ranged from approximately 170 m/s at 15 Hz to 250 m/s at 5 Hz. These results are consistent with other results of active-source DAS and seismometer records obtained at the Garner Valley site (e.g., Stokoe et al. 2004). This analysis is

  18. Insect-protected event DAS-81419-2 soybean (Glycine max L.) grown in the United States and Brazil is compositionally equivalent to nontransgenic soybean.

    PubMed

    Fast, Brandon J; Schafer, Ariane C; Johnson, Tempest Y; Potts, Brian L; Herman, Rod A

    2015-02-25

    The transgenic soybean event DAS-81419-2 contains genes that encode the Cry1F, Cry1Ac, and PAT proteins. Cry1F and Cry1Ac provide protection against key lepidopteran insect pests, while PAT confers tolerance to the herbicide glufosinate. To satisfy regulatory requirements for the safety evaluation of transgenic crops, studies were conducted in the United States and Brazil to evaluate the nutrient and antinutrient composition of event DAS-81419-2 soybean. On the basis of the results of these studies, event DAS-81419-2 soybean is compositionally equivalent to nontransgenic soybean. This conclusion concurs with numerous other published studies in soybean and other crops where compositional equivalence between the transgenic crop and its nontransgenic comparator has been demonstrated.

  19. Insect-Protected Event DAS-81419-2 Soybean (Glycine max L.) Grown in the United States and Brazil Is Compositionally Equivalent to Nontransgenic Soybean

    PubMed Central

    2015-01-01

    The transgenic soybean event DAS-81419-2 contains genes that encode the Cry1F, Cry1Ac, and PAT proteins. Cry1F and Cry1Ac provide protection against key lepidopteran insect pests, while PAT confers tolerance to the herbicide glufosinate. To satisfy regulatory requirements for the safety evaluation of transgenic crops, studies were conducted in the United States and Brazil to evaluate the nutrient and antinutrient composition of event DAS-81419-2 soybean. On the basis of the results of these studies, event DAS-81419-2 soybean is compositionally equivalent to nontransgenic soybean. This conclusion concurs with numerous other published studies in soybean and other crops where compositional equivalence between the transgenic crop and its nontransgenic comparator has been demonstrated. PMID:25641393

  20. Priming index of the Spanish word fragments from the Dasí, Soler, and Ruiz (2004) database.

    PubMed

    Dasí, Carmen; Soler, María José; Ruiz, Juan Carlos

    2007-08-01

    Word-fragment completion is a frequently used test in implicit memory research. A database of 196 Spanish fragments was recently published (Dasí, Soler, & Ruiz, 2004) in which the fragments were described for indices, such as difficulty, familiarity, frequency, number of meanings, and so on (www.psychonomic.org/archive). In this work, a new index, the priming index, is described for the same 196 fragments. This index is calculated for each fragment by subtracting the difficulty index (the proportion of correct completion when the fragment is not studied) from the proportion of correct completion when the fragment is studied, and it means the capacity of an item to be primed. In order to determine whether the new index performs well, we have replicated some important experimental effects, such as priming, frequency, and difficulty. We consider that this index can help researchers to better select stimuli for fragment-completion tasks.

  1. Development of a surface-wave imaging system for geotechnical applications based on distributed acoustic sensing (DAS) and ambient noise interferometry

    NASA Astrophysics Data System (ADS)

    Ajo Franklin, J. B.; Daley, T. M.; Freifeld, B. M.; Tang, D. G.; Zhang, R.; Wagner, A. M.; Dou, S.; Lindsey, N.; Bjella, K.; Pevzner, R.

    2014-12-01

    Distributed fiber-optic sensing methods have been used since the 1980's for continuous monitoring of near-surface soil properties, typically exploiting Raman scattering to measure temperature (DTS) or stimulated Brillouin scattering to measure strain (DSS). Recent advances in high speed measurement of Rayleigh scattering has enabled distributed recording of seismic waves over long sections of fiber; this approach, referred to as distributed acoustic sensing (DAS) has the potential to allow nearly continuous monitoring of near-surface mechanical properties, a crucial target for geotechnical management of infrastructure dependent on soil strength. We present initial results from our effort to build a real-time soil property monitoring system based on DAS; our approach employs seismic interferometry and dispersion analysis of ambient noise generated by infrastructure to provide a continuously updated model of shear modulus. Our preliminary results include an in-depth investigation of DAS fiber response in the context of active sources; this component of our study verifies classical models for the azimuthal response of straight fibers to propagating surface waves. We also explore the "noisescape" of linear infrastructure and show a usable seismic signal band of 8-40 hz at a series of sites, primarily consisting of Rayleigh waves. Finally, we present preliminary results from a DAS monitoring array installed at the Richmond Field Station near a heavily used road and compare interferometric processing of the acquired data to that generated by surface deployment of geophones.

  2. Novas determinações dos parâmetros atmosféricos das estrelas anãs brancas DA

    NASA Astrophysics Data System (ADS)

    Giovannini, O.; Costa, A. F. M.; Kepler, S. O.

    2003-08-01

    Nós temos selecionado uma amostra de estrelas anãs brancas DA (atmosfera de hidrogênio) a partir dos índices de Strömgren cujos valores estão próximos a região de instabilidade das estrelas anãs brancas DA variáveis, as chamadas estrelas DAV ou ZZ Ceti. O objetivo é determinar os parâmetros fundamentais (temperatura efetiva, Teff, aceleração da gravidade, log g, e massa) destas estrelas para verificar quais os parâmetros estelares estão envolvidos com o mecanismo de pulsação das estrelas DAV. Nós obtemos, até agora, mais de 120 espectros óticos de estrelas DA. Entre as estrelas selecionadas há 20 estrelas variáveis (DAV). Assim, podemos verificar se existem ou não estrelas não variáveis dentro da faixa de instabilidade das estrelas ZZ Ceti. Neste trabalho nós apresentamos a determinação dos parâmetros atmosféricos (temperatura efetiva, Teff, e aceleração da gravidade, log g) das estrelas anãs brancas DA usando os novos modelos de atmosfera ML2/a = 0.6. Estes modelos têm sido utilizados recentemente por fornecerem uma excelente consistência interna na determinação das temperaturas nas regiões do ultra-violeta e ótico. Os parâmetros atmosféricos são determinados espectroscopicamente através da comparação do fluxo de energia das linhas de Balmer (Hb à H9) entre os espectros observados e sintéticos (gerados pelos modelos de atmosfera). As temperaturas obtidas com os novos modelos são, em geral, menores (~ 1000 K menos) que as temperaturas determinadas anteriormente, com modelos ML1. Os valores de log g não mudaram significativamente (menos de 10%). A faixa de instabilidade das DAVs está entre 11000 e 13000 K, consistente com dados de outros autores.

  3. Three genes encoding citrate synthases in Saccharopolyspora erythraea are regulated by the global nutrient-sensing regulators GlnR, DasR, and CRP.

    PubMed

    Liao, Cheng-Heng; Yao, Li-Li; Ye, Bang-Ce

    2014-10-08

    Saccharopolyspora erythraea has three citrate synthases encoded by gltA-2, citA, and citA4. Here, we characterized and identified the expression and regulatory properties of these synthases. Three pleiotropic global regulatory proteins of S. erythraea - CRP, GlnR, and DasR - are involved in carbon metabolism, nitrogen metabolism, and amino-sugar (chitin and GlcNAc) metabolism. Using electrophoretic mobility shift assays (EMSAs), we identified these regulators as proteins that bind directly to the promoter regions of all citrate synthase genes (gltA-2, citA, and citA4). Footprinting assays indicated the exact protect sequences of CRP, GlnR, and DasR on the promoter region of gltA-2, revealing binding competition between GlnR and DasR. Moreover, by comparing the transcription levels of citrate synthase genes between parental and glnR mutant or dasR mutant strains, or by comparing the transcription response of citrate synthases under various nutrient conditions, we found that GlnR and DasR negatively regulated citA and citA4 transcription but had no regulatory effects on the gltA-2 gene. Although no CRP mutant was available, the results indicated that CRP was a cAMP-binding receptor affecting gltA-2 transcription when the intracellular cAMP concentration increased. Thus, an overall model of CS regulation by C and/or N metabolism regulators and cAMP receptor protein was proposed.

  4. Evaluation of corn grain with the genetically modified input trait DAS-59122-7 fed to growing-finishing pigs.

    PubMed

    Stein, H H; Rice, D W; Smith, B L; Hinds, M A; Sauber, T E; Pedersen, C; Wulf, D M; Peters, D N

    2009-04-01

    A growth performance experiment was conducted to assess the feeding value of a double-stacked transgenic corn grain for growing-finishing pigs. The genetically modified corn grain contained event DAS-59122-7, which expresses the Cry34/35Ab1 binary insecticidal protein for the control of corn rootworm. This modified transgenic grain is resistant to western corn rootworm and is also tolerant to herbicides containing the active ingredient glufosinate-ammonium. The modified grain (59122), a nontransgenic near-isoline grain (control corn), and a commercial corn (Pioneer brand hybrid 35P12) were grown in a 2005 production trial in individually isolated plots that were located 201 m apart. A total of 108 pigs were allotted to corn-soybean meal diets containing 1 of the 3 grains as the sole source of corn. There were 3 pigs per pen and 12 replicate pens per treatment. Pigs were fed grower diets from 37 to 60 kg, early finisher diets from 60 to 90 kg, and late finisher diets from 90 to 127 kg. Within each phase, data for ADG, ADFI, and G:F were calculated. At the conclusion of the experiment, pigs were slaughtered and data for carcass quality were collected. Differences between 59122 and the control corn were evaluated, with statistical significance at P<0.05. No differences in ADG, ADFI, or G:F between pigs fed the control corn and pigs fed the modified corn were observed during the grower, early finisher, or late finisher phases. For the entire experimental period, no difference between pigs fed the control and the 59122 corn were observed for final BW (128.9 vs. 127.1 kg), ADG (1.02 vs. 1.00 kg), ADFI (2.88 vs. 2.80 kg), or G:F (0.356 vs. 0.345 kg/kg). Likewise, no differences in dressing percentage (76.48 vs. 76.30%), LM area (49.8 vs. 50.4 cm(2)), 10th-rib back fat (2.20 vs. 2.12 cm), and carcass lean content (52.9 vs. 53.4%) were observed between pigs fed the control and the 59122 corn grain. It was concluded that the nutritional value of the modified transgenic corn

  5. Simulation of the single-vibronic-level emission spectra of HAsO and DAsO

    NASA Astrophysics Data System (ADS)

    Mok, Daniel K. W.; Lee, Edmond P. F.; Dyke, John M.

    2016-05-01

    The single-vibronic-level (SVL) emission spectra of HAsO and DAsO have been simulated by electronic structure/Franck-Condon factor calculations to confirm the spectral molecular carrier and to investigate the electronic states involved. Various multi-reference (MR) methods, namely, NEVPT2 (n-electron valence state second order perturbation theory), RSPT2-F12 (explicitly correlated Rayleigh-Schrodinger second order perturbation theory), and MRCI-F12 (explicitly correlated multi-reference configuration interaction) were employed to compute the geometries and relative electronic energies for the X ˜ 1 A ' and A ˜ 1 A ″ states of HAsO. These are the highest level calculations on these states yet reported. The MRCI-F12 method gives computed T0 (adiabatic transition energy including zero-point energy correction) values, which agree well with the available experimental T0 value much better than previously computed values and values computed with other MR methods in this work. In addition, the potential energy surfaces of the X ˜ 1 A ' and A ˜ 1 A ″ states of HAsO were computed using the MRCI-F12 method. Franck-Condon factors between the two states, which include anharmonicity and Duschinsky rotation, were then computed and used to simulate the recently reported SVL emission spectra of HAsO and DAsO [R. Grimminger and D. J. Clouthier, J. Chem. Phys. 135, 184308 (2011)]. Our simulated SVL emission spectra confirm the assignments of the molecular carrier, the electronic states involved, and the vibrational structures observed in the SVL emission spectra but suggest a loss of intensity in the reported experimental spectra at the low emission energy region almost certainly due to a loss of responsivity near the cutoff region (˜800 nm) of the detector used. Computed and experimentally derived re (equilibrium) and/or r0 {the (0,0,0) vibrational level} geometries of the two states of HAsO are discussed.

  6. Nutrient budgets (C, N and P) and trophic dynamics of a Brazilian tropical estuary: Barra das Jangadas.

    PubMed

    Noriega, Carlos E D; Araujo, Moacyr

    2011-06-01

    This paper focuses on the nutrient dynamics of a tropical estuary on the northeastern Brazilian coast, studied using the LOICZ biogeochemical budgeting protocol. We describe the methodology and assumptions underlying this model. Input data (monthly for rainfall, evaporation, river discharge, and concentrations of salt, phosphorus and nitrogen) were obtained during field campaigns in the Barra das Jangadas Estuary (BJE) over a 5 years period (1999 to 2003). Mass balance results indicate large inputs of nutrients to the system. The model shows that the seasonal variation of the Net Ecosystem Metabolism (NEM) indicates that the system passes from a stage of organic matter liquid production and mineralization during the dry season (-0.5 mmoles C m(-2) d(-1)) to liquid mineralization during the rainy season (-19 mmoles C m(-2) d(-1)). We suggest that the system varies slightly between autotrophy and heterotrophy during the year due to the rainfall regime, human activities in the basin (density population and sugarcane plantations), and associated DIP riverine loads. High per capita loads of N and P indicate a high population density and high runoff. The application of flux balance modeling was useful to understand the nutrient dynamics of this typical small tropical estuary.

  7. Stacking transgenic event DAS-Ø15Ø7-1 alters maize composition less than traditional breeding.

    PubMed

    Herman, Rod A; Fast, Brandon J; Scherer, Peter N; Brune, Alyssa M; de Cerqueira, Denise T; Schafer, Barry W; Ekmay, Ricardo D; Harrigan, George G; Bradfisch, Greg A

    2017-02-20

    The impact of crossing ("stacking") genetically modified (GM) events on maize-grain biochemical composition was compared with the impact of generating non-GM hybrids. The compositional similarity of seven GM stacks containing event DAS-Ø15Ø7-1 and their matched non-GM near-isogenic hybrids (iso-hybrids) was compared with the compositional similarity of concurrently grown non-GM hybrids and these same iso-hybrids. Scatter plots were used to visualize comparisons among hybrids and a coefficient of identity (percent of variation explained by line of identity) was calculated to quantify the relationships within analyte profiles. The composition of GM breeding stacks was more similar to the composition of iso-hybrids than was the composition of non-GM hybrids. Non-GM breeding more strongly influenced crop composition than did transgenesis or stacking of GM events. These findings call into question the value of uniquely requiring composition studies for GM crops, especially for breeding stacks composed of GM events previously found to be compositionally normal. This article is protected by copyright. All rights reserved.

  8. Acute postsurgical suppurative parotitis: current prevalence at Hospital das Clínicas, São Paulo University Medical School.

    PubMed

    Belczak, Sergio Quilici; Cleva, Roberto D E; Utiyama, Edivaldo M; Cecconello, Ivan; Rasslan, Samir; Parreira, José Gustavo

    2008-01-01

    Postsurgical acute suppurative parotitis is a bacterial gland infection that occurs from a few days up to some weeks after abdominal surgical procedures. In this study, the authors analyze the prevalence of this complication in Hospital das Clínicas/São Paulo University Medical School by prospectively reviewing the charts of patients who underwent surgeries performed by the gastroenterological and general surgery staff from 1980 to 2005. Diagnosis of parotitis or sialoadenitis was analyzed. Sialolithiasis and chronic parotitis previous to hospitalization were exclusion criteria. In a total of 100,679 surgeries, 256 patients were diagnosed with parotitis or sialoadenitis. Nevertheless, only three cases of acute postsurgical suppurative parotitis associated with the surgery were identified giving an incidence of 0.0028%. All patients presented with risk factors such as malnutrition, immunosuppression, prolonged immobilization and dehydration. In the past, acute postsurgical suppurative parotitis was a relatively common complication after major abdominal surgeries. Its incidence decreased as a consequence of the improvement of perioperative antibiotic therapy and postoperative support. In spite of the current low incidence, we believe it is important to identify risks and diagnose as quick as possible, in order to introduce prompt and appropriate therapeutic measures and avoid potentially fatal complications with the evolution of the disease.

  9. Free convection in a parallelogrammic porous cavity filled with a nanofluid using Tiwari and Das' nanofluid model.

    PubMed

    Ghalambaz, Mohammad; Sheremet, Mikhail A; Pop, Ioan

    2015-01-01

    The free convection heat transfer of Cu-water nanofluids in a parallelogrammic enclosure filled with porous media is numerically analyzed. The bottom and top of the enclosure are insulated while the sidewalls are subject to limited temperature difference. The Darcy flow and the Tiwari and Das' nanofluid models are considered. The governing dimensionless partial differential equations are numerically solved using a finite difference code. The results are reported for isotherms and streamlines as well as Nusselt number as a function of the volume fraction of nanoparticles, porosity, types of the porous matrix, inclination angle, aspect ratio and different Rayleigh numbers. It is found that the presence of the nanoparticles inside the enclosure deteriorates the heat transfer rate, which is caused due to the increase of dynamic viscosity by the presence of nanoparticles. Therefore, in applications in which the nanofluids are used for their advantages, such as enhanced dielectric properties or antibacterial properties, more caution for the heat transfer design of the enclosure is necessary.

  10. Wood anatomy of Mollinedia glabra (Spreng.) Perkins (Monimiaceae) in two Restinga Vegetation Formations at Rio das Ostras, RJ, Brazil.

    PubMed

    Novaes, Fernanda da S; Callado, Cátia H; Pereira-Moura, Maria Verônica L; Lima, Helena R P

    2010-12-01

    This paper aimed to characterize the anatomical structure of the wood of specimens of Mollinedia glabra (Spreng.) Perkins growing in two contiguous formations of restinga vegetation at Praia Virgem, in the municipality of Rio das Ostras, RJ. Both the Open Palmae (OPS) and the Sandy Strip Closed Shrub (SSCS) formations are found in coastal regions that receive between 1,100 and 1,300 mm of rainfall per year. Sapwood samples were collected in both formations. Typical anatomical features for this species include: solitary vessels, radial multiples or clusters elements, that are circular to angular in outline, 5-15 barred scalariform perforation plates, wood parenchyma scanty, septate fiber-tracheids, and wide multiseriate rays with prismatic crystals. Statistical analyses indicated a significant increase in the frequency of vessel elements and an increase in fiber-tracheid diameters in OPS individuals. These characteristics are considered structural adaptations to increased water needs caused by a greater exposure to sunlight. Continuous pruning may be responsible for the tyloses observed in OPS plants. The greater lengths and higher frequencies of the rays in SSCS trees may be due to the greater diameters of their branches. Our results suggest that M. glabra develops structural adaptations to the restinga micro-environmental variations during its development.

  11. Common Data Acquisition Systems (DAS) Software Development for Rocket Propulsion Test (RPT) Test Facilities - A General Overview

    NASA Technical Reports Server (NTRS)

    Hebert, Phillip W., Sr.; Hughes, Mark S.; Davis, Dawn M.; Turowski, Mark P.; Holladay, Wendy T.; Marshall, PeggL.; Duncan, Michael E.; Morris, Jon A.; Franzl, Richard W.

    2012-01-01

    The advent of the commercial space launch industry and NASA's more recent resumption of operation of Stennis Space Center's large test facilities after thirty years of contractor control resulted in a need for a non-proprietary data acquisition system (DAS) software to support government and commercial testing. The software is designed for modularity and adaptability to minimize the software development effort for current and future data systems. An additional benefit of the software's architecture is its ability to easily migrate to other testing facilities thus providing future commonality across Stennis. Adapting the software to other Rocket Propulsion Test (RPT) Centers such as MSFC, White Sands, and Plumbrook Station would provide additional commonality and help reduce testing costs for NASA. Ultimately, the software provides the government with unlimited rights and guarantees privacy of data to commercial entities. The project engaged all RPT Centers and NASA's Independent Verification & Validation facility to enhance product quality. The design consists of a translation layer which provides the transparency of the software application layers to underlying hardware regardless of test facility location and a flexible and easily accessible database. This presentation addresses system technical design, issues encountered, and the status of Stennis' development and deployment.

  12. Das wissenschaftliche Handbuch

    NASA Astrophysics Data System (ADS)

    Luckenbach, Reiner; Sunkel, Josef

    1981-02-01

    The 100th anniversary of Beilstein's Handbook of Organic Chemistry, founded in 1881, merits a brief description of the principal concepts and goals of the literary genre “scientific handbook” in general. Systematic arrangement, critical data and fact evaluation, thoroughness and reliability are among these goals, thus providing the handbook user with a concise compilation of carefully checked and cross-referenced information in his particular field of interest.

  13. Variation of the anthropic vulnerability in Ribeirão das Pedras watershed in Campinas/SP - Brazil.

    NASA Astrophysics Data System (ADS)

    Damame, Desirée; Longo, Regina; Ribeiro, Admilson; Fengler, Felipe

    2015-04-01

    The human actions has caused over the years profound changes in environmental quality in urban ecosystems suffering losses in the quality of air, soil , water and vegetation also the quality of life of the population that inhabit these areas . The study area is characterized by being a highly urbanized watershed, with about 43 % of its area covered by buildings, houses , and commercial and industrial establishments . Called the Ribeirão das Pedras Basin, located in Campinas / SP - Brazil and is bounded by coordinates 22˚47'10 '' and 22˚52'20 '' S , and 47˚ 07'15 '' and 46˚ 02 ' 15' ' . Has an average temperature of 22.4 ° C and average annual rainfall of 1424.5 mm . It has an area of about 42 km² . This is located two universities and a large mall. It also demands a strong agriculture , which occupies about 30 % of the area . It has also been part of two major forest reserves of the municipality, the Forest Santa Geneva and the Forest of Quilombo , both added to other small fragments overlying only about 6% of the total basin area . Avalição to environmental quality , the analysis of the vulnerability of urban watershed becomes an important environmental management tool. The vulnerability can be defined by susceptibility to changes of environment in its initial state , a current tax status by human intervention , and is almost always associated with risk , and the intensity at which such projects in one place, person or structure. In this context , this study aimed to assess environmental vulnerability in an urban watershed coming under increasing human pressures , especially in recent years . For this analysis were prepared soil graphics, slope , elevation and land use and land cover for the years 2009 and 2014 , generating with these , comparative anthropic vulnerability maps of the past five years. Crafting vulnerability maps is a sensitivity in order to enable appropriate management of biotic systems. With the results can be seen that the variation of

  14. Comparative morphology of the reproductive system of seven species of ostariophysan fishes from the upper Das Velhas River, Brazil.

    PubMed

    Melo, Rafael Magno Costa; Gomes, Débora Diniz; Moreira, Davidson Peruci; Gomes, Maysa Regina; Bazzoli, Nilo; Rizzo, Elizete

    2017-02-01

    The success of fishes in different environments is related with the variation of reproductive strategies developed by the systematic group, which is reflected in the morphology of the reproductive system and can have ecological and evolutionary implications. This study comparatively analyzed the morphological characteristics of the male and female reproductive systems of ostariophysan fish species from the upper Das Velhas River in the São Francisco River basin, Brazil. In order to accomplish this, 393 specimens belonging to seven fish species were sampled between April 2010 and June 2015 for histological, ultrastructural, histochemical, and morphometric analyses. All the species examined have anastomosing tubular testes with unrestricted distribution of spermatogonia. Astyanax bimaculatus, A. fasciatus, A. scabripinnis, and Harttia torrenticola had their spermatozoa embedded in a glycoprotein secretion within the tubule lumen. Most species had type I spermiogenesis, whereas Rhamdia quelen had type III spermiogenesis. While all females examined had asynchronous oocyte development, there were remarkable morphological, histochemical, and morphometric differences in the ovarian follicles and enveloping layers. Hoplias malabaricus and H. torrenticola, which exhibit parental care behaviour, had a significantly larger diameter of vitellogenic oocytes and larger spermatozoa nuclei. Apareiodon ibitiensis, H. torrenticola, and A. scabripinnis, species that have rheophilic preferences, exhibited a thicker zona radiata than the other species examined. The follicular cells of R. quelen and H. torrenticola were columnar and produced a jelly coat and mucosubstances, respectively. The females of the seven fish species studied show a correlation of the reproductive strategies with the reproductive system morphology, while males retained more similar morphological characteristics between species. J. Morphol. 278:170-181, 2017. © 2016 Wiley Periodicals,Inc.

  15. Ventos em supergigantes B[e] das nuvens de Magalhães e da Galáxia

    NASA Astrophysics Data System (ADS)

    de Araújo, F. X.; Pilling, D. A.; Pereira, C. B.; Fernandes, M. B.

    2003-08-01

    As Supergigantes B[e] apresentam as seguintes características: (i) alta luminosidade; (ii) espectro típico de estrelas de tipo B; (iii) linhas permitidas e proibidas em emissão de metais de baixa ionização, especialmente FeII; (iv) linhas de Balmer, e por vêzes também dos ions HeI e FeII, com perfis tipo P Cygni indicativos de altas taxas de perda de massa. Atualmente estamos desenvolvendo um projeto que visa comparar as propriedades fisicas (principalmente e v¥) dos ventos destes objetos nas Nuvens de Magalhães e na Galaxia. O objetivo é estudar a influência da metalicidade. No presente painel apresentamos uma determinação das velocidades terminais de 11 estrelas, sendo 4 na GNM (Hen S111, 66, R126 e Hen S93), 4 na PNM (Hen S18, S23, S65 e R4) e 3 na Galaxia (CPD-529243, MWC 300 e GG Car). Nossos dados são espectros de alta resolução obtidos no telescópio 1.52m do ESO com o espectrógrafo FEROS. Para determinar as velocidades terminais usamos as linhas Hd e HeI 3888 Å cujas componentes em absorção costumam estar livres de "blends" e estruturas. Nossos resultados sugerem que as velocidades de expansão na GNM são maiores (ainda que apenas ligeiramente) do que aquelas da PNM, como esperado. No entanto, os objetos da Galaxia não parecem seguir a mesma tendência.

  16. Bottom Characterization with High Resolution Sonar Data and Geochemical Analyses of an Uninvestigated Cone in Lagoa das Furnas on São Miguel Island, Azores Archipelago

    NASA Astrophysics Data System (ADS)

    Andersson, T.

    2015-12-01

    Lagoa das Furnas is a crater lake located in an area exposed to geohazards from earthquakes and volcanic activity on the island São Miguel in the Azores Archipelago. The Furnas volcanic center has a long history of earthquakes and volcanic activity. The area is relatively well studied except for the lake floor. Therefore, a high resolution geophysical and geological mapping survey was conducted at Lagoa das Furnas. Sidescan sonar was used to map the surface of the lake floor and single beam sonar was used to acquire sub-bottom profiles. In addition to the geophysical mapping, sediment surface sampling and core drilling were carried out followed by geochemical analyses of the retrieved material. The mapped data permitted a characterization of the floor of Lagoa das Furnas and revealed several volcanic features including fumarolic activity and a previously uninvestigated volcanic cone in the southern part of the lake. In order to unravel the origin of this cone several methods were applied, including analyses of tephra and minerals collected from the cone itself and from nearby deposits of two known eruptions, Furnas I and Furnas 1630. Sedimentological, petrological, geochemical and geochronological studies of pyroclastic deposits from the cone suggest a subaqueous eruption linked to the Furnas 1630 eruption. The chemistry of glass and crystal fragments sampled from the cone suggests that it is composed of more evolved magma than that of the main Furnas 1630, implying that the lake cone is likely a product of the last eruptional phase. According to historical records, two of three lakes were lost due the Furnas 1630 eruption. The results of this study show that the remaining lake is most likely Lagoa das Furnas, which consequently must have existed before the 1630 eruption.

  17. Soil gas Rn monitoring at Chã das Caldeiras prior the 2014-15 Fogo eruption, Cape Verde

    NASA Astrophysics Data System (ADS)

    Padilla, Germán; Barrancos, José; Dionis, Samara; Fernandes, Paulo; Pérez, Nemesio M.; Sagiya, Takeshi; Padrón, Eleazar; Melián, Gladys V.; Hernández, Pedro A.; Silva, Sónia; Pereira, José Manuel; Rodríguez, Fátima; Asensio-Ramos, María; Calvo, David; Semedo, Helio

    2015-04-01

    Since 2007 the ITER-INVOLCAN/UNICV-OVCV/SNPC research team has implemented a geochemical program for the volcanic surveillance of Fogo volcano by means of applying different geochemical methods in a regularly basis (diffuse degassing surveys, fumarole gas sampling, etc.). This program was improved by setting up a geochemical permanent station (CHA01) to perform continuous measurements of soil gas radon (222Rn) and thoron (220Rn) activities at Chã das Caldeiras, more specific in Portela village, since April 20, 2013. Both gases are characterized to ascend towards the surface mainly through cracks or faults via diffusion and/or advection mechanisms dependent of both soil porosity and permeability, which in turn vary as a function of the stress/strain changes at depth. Measurements of 222Rn and 220Rn activities were performed by an alpha-spectrometer after pumping the soil gas from a thermally isolated PVC pipe inserted 1m in the ground. Even though during the study period the recorded data did not show high 222Rn activity values, a change in the temporal evolution of soil gas 222Rn activity was observed. During the first six months, from April to October, 2013, recorded time series of 222Rn and 220Rn activities showed normal background levels with values of 80.5 and 55.2 Bqm-3, respectively. However, from October, 2013, to February, 2014, 222Rn time series showed an increase trend reaching peak values of 396 Bqm-3 and having an average activity of 134 Bqm-3 until the removal of the station on November 25, 2014 due to the potential danger of being destroyed by the lava flows. The observed increase in the soil gas 222Rn activity from October 2013 to February 2014 occurs almost at the same time of slight observed changes in the vertical displacements detected by the geodetic network installed at the Fogo Island by the ITER-INVOLCAN/UNICV-OVCV/SNPC/Nagoya University research team. Since seismic data are not available, we cannot conclude if the observed changes in soil

  18. Data Integration Acquired from Micro-Uav and Terrestrial Laser Scanner for the 3d Mapping of Jesuit Ruins of São Miguel das Missões

    NASA Astrophysics Data System (ADS)

    Reiss, M. L. L.; da Rocha, R. S.; Ferraz, R. S.; Cruz, V. C.; Morador, L. Q.; Yamawaki, M. K.; Rodrigues, E. L. S.; Cole, J. O.; Mezzomo, W.

    2016-06-01

    The Jesuit Missions the Guaranis were one of the great examples of cultural, social, and scientific of the eighteenth century, which had its decline from successive wars that followed the exchange of territories domain occupied by Portugal and Spain with the Madrid Treaty of January 13, 1750. One of the great examples of this development is materialized in the ruins of 30 churches and villages that remain in a territory that now comprises part of Brazil, Argentina and Paraguay. These Churches, São Miguel das Missões is among the Brazilian ruins, the best preserved. The ruins of São Miguel das Missões were declared a UNESCO World Cultural Heritage in 1983 and the Institute of National Historical Heritage (IPHAN) is the Brazilian Federal agency that manages and maintains this heritage. In order to produce a geographic database to assist the IPHAN in the management of the Ruins of São Miguel das Missões it was proposed a three-dimensional mapping of these ruins never performed in this location before. The proposal is integrated data acquired from multiple sensors: two micro-UAV, an Asctec Falcon 8 (rotary wing) and a Sensefly e-Bee (fixed wing); photos from terrestrial cameras; two terrestrial LIDAR sensors, one Faro Focus 3D S-120 and Optec 3D-HD ILRIS. With this abundance of sensors has been possible to perform comparisons and integration of the acquired data, and produce a 3D reconstruction of the church with high completeness and accuracy (better than 25 mm), as can be seen in the presentation of this work.

  19. Challenges for bathing in rivers in terms of compliance with coliform standards. Case study in a large urbanized basin (das Velhas River, Brazil).

    PubMed

    von Sperling, Marcos; von Sperling, Eduardo

    2013-01-01

    This paper presents a case study on the prospects of bathing in a large water course (das Velhas River, Brazil), which crosses the important metropolitan region of Belo Horizonte (25 municipalities), receiving several point and diffuse discharges. The studies were carried out based on a mathematical simulation of thermotolerant coliforms over 227 km of the river, using an adaptation of the Qual2E model (model Qual-UFMG). Simulations of intervention scenarios were made for the current conditions, with three reference flows for the das Velhas River, tributaries and direct contribution: Q7,10 (representative of low-flow conditions), Q50 (average conditions) and Q10 (rainy season). The intervention scenarios simulated were: (a) current conditions without intervention; (b) scenario with effluent disinfection in the two largest wastewater treatment plants in the basin (around 2.4 million inhabitants); (c) scenario with 95% sewage collection and treatment, with disinfection in all municipalities of the study area; (d) scenario with the calculation of values required for the coverage of sewage treatment and coliform removal efficiencies based on a mathematical optimization process. The monitoring data and results of all simulations indicated improvement in coliform concentration as the river flows downstream. However, results suggested that disinfection per se is not enough. Even under hypothetical conditions of excellent sanitary infrastructure for a developing country, coverage of collection and treatment of 95% of the generated sewage, and treatment with disinfection at all wastewater treatment plants, concentrations of thermotolerant coliforms in das Velhas River are likely to be above the maximum allowable of 1,000 MPN/100 mL for bathing purposes. The mathematical optimization indicated the need for very high percentages of sewage treatment coverage (near 100%, i.e. universality of collection and treatment) and implementation of disinfection in most treatment plants

  20. DasPy 1.0 - the Open Source Multivariate Land Data Assimilation Framework in combination with the Community Land Model 4.5

    NASA Astrophysics Data System (ADS)

    Han, X.; Li, X.; He, G.; Kumbhar, P.; Montzka, C.; Kollet, S.; Miyoshi, T.; Rosolem, R.; Zhang, Y.; Vereecken, H.; Franssen, H.-J. H.

    2015-08-01

    Data assimilation has become a popular method to integrate observations from multiple sources with land surface models to improve predictions of the water and energy cycles of the soil-vegetation-atmosphere continuum. Multivariate data assimilation refers to the simultaneous assimilation of observation data from multiple model state variables into a simulation model. In recent years, several land data assimilation systems have been developed in different research agencies. Because of the software availability or adaptability, these systems are not easy to apply for the purpose of multivariate land data assimilation research. We developed an open source multivariate land data assimilation framework (DasPy) which is implemented using the Python script language mixed with the C++ and Fortran programming languages. LETKF (Local Ensemble Transform Kalman Filter) is implemented as the main data assimilation algorithm, and uncertainties in the data assimilation can be introduced by perturbed atmospheric forcing data, and represented by perturbed soil and vegetation parameters and model initial conditions. The Community Land Model (CLM) was integrated as the model operator. The implementation allows also parameter estimation (soil properties and/or leaf area index) on the basis of the joint state and parameter estimation approach. The Community Microwave Emission Modelling platform (CMEM), COsmic-ray Soil Moisture Interaction Code (COSMIC) and the Two-Source Formulation (TSF) were integrated as observation operators for the assimilation of L-band passive microwave, cosmic-ray soil moisture probe and land surface temperature measurements, respectively. DasPy has been evaluated in several assimilation studies of neutron count intensity (soil moisture), L-band brightness temperature and land surface temperature. DasPy is parallelized using the hybrid Message Passing Interface and Open Multi-Processing techniques. All the input and output data flows are organized efficiently

  1. Alterations in the immunohistochemical expression of Das-1 and CG-3 in colonic mucosal biopsy specimens helps distinguish ulcerative colitis from Crohn disease and from other forms of colitis.

    PubMed

    Yantiss, Rhonda K; Das, Kiron M; Farraye, Francis A; Odze, Robert D

    2008-06-01

    Distinction between ulcerative colitis (UC) and Crohn disease (CD) in mucosal biopsies is often difficult. Das-1 and CG-3 are monoclonal antibodies directed against an unknown colonic epithelial protein and human tropomyosin isoform-5, respectively, both show altered expression in patients with UC. In this study, we evaluated the utility of Das-1 and CG-3 in distinguishing UC from CD and from other types of colitis. One colonic biopsy specimen from each of 85 patients with confirmed UC (n=25), CD (n=15), lymphocytic (n=15), collagenous (n=15), and ischemic (n=15) colitis, and also 10 samples from normal controls, were stained for Das-1 and CG-3 using standard techniques. Reactivity for Das-1 and CG-3 was noted to be absent or present, and the location (ie, surface+/-crypt epithelium) and degree (weak or strong) of CG-3 staining was recorded. Loss of Das-1 staining occurred more frequently in UC (96%) compared with CD (20%), lymphocytic (20%), collagenous (13%), and ischemic colitis (0%) cases, as well as controls (10%, P<0.001 for all comparisons). CG-3 positivity in crypt epithelium was significantly more common in UC (52%) compared with the other groups (P< or =0.02 for all comparisons). The combination of strong crypt CG-3 staining and loss of Das-1 staining was noted in 44% of UC cases, but not in any other type of colitis (P=0.003 for all comparisons). We conclude that the patterns of Das-1 and CG-3 staining in colonic mucosal biopsies may be clinically useful in distinguishing UC from CD and from other colitidies.

  2. Agronomic performance of insect-protected and herbicide-tolerant MON 89034 × TC1507 × NK603 × DAS-40278-9 corn is equivalent to that of conventional corn.

    PubMed

    Cerqueira, Denise T Rezende de; Schafer, Ariane C; Fast, Brandon J; Herman, Rod A

    2017-03-31

    Agronomic characteristics of genetically modified (GM) MON 89034 × TC1507 × NK603 × DAS-40278-9 (PowerCore™ Enlist™), MON 89034 × TC1507 × NK603 (PowerCore™), and DAS-40278-9 (Enlist™) corn, a non-GM near-isogenic hybrid, and two commercial non-GM hybrids were assessed in a field study to determine if the agronomic performance of the GM corn hybrids is equivalent to that of non-transgenic hybrid corn. The MON 89034 × TC1507 × NK603 × DAS-40278-9 hybrid corn was developed through stacking of four individual transgenic events, MON 89034, TC1507, NK603, and DAS-40278-9 by traditional breeding and contains the cry1A.105 and cry2Ab2 (MON 89034), cry1F and pat (TC1507), cp4 epsps (NK603) and aad-1 (DAS-40278-9) transgenes. These transgenes encode the proteins Cry1A.105, Cry2Ab2, and Cry1F, which confer insect resistance, PAT, CP4 EPSPS, and AAD-1, which confer herbicide tolerance. The following agronomic characteristics were assessed in the study: initial and final stand count, seedling vigor, time to silk, time to pollen shed, pollen viability, plant height, ear height, stalk lodging, root lodging, days to maturity, stay green, disease incidence, insect damage, herbicide injury, and yield. The agronomic assessment was conducted in two regions of Brazil (Indianopolis-MG; Cravinhos-SP). The agronomic attributes for all GM entries were statistically indistinguishable from the non-GM near-isogenic hybrid. In addition, most of the agronomic assessments fell within the range of the commercial varieties included in the study. Taken together, MON 89034 × TC1507 × NK603 × DAS-40278, MON 89034 × TC1507 × NK603, and DAS-40278-9 were found to be agronomically equivalent to non-GM corn.

  3. Metabolism and Residues of 2,4-Dichlorophenoxyacetic Acid in DAS-40278-9 Maize (Zea mays) Transformed with Aryloxyalkanoate Dioxygenase-1 Gene.

    PubMed

    Zhou, Xiao; Rotondaro, Sandra L; Ma, Mingming; Rosser, Steve W; Olberding, Ed L; Wendelburg, Brian M; Adelfinskaya, Yelena A; Balcer, Jesse L; Blewett, T Craig; Clements, Bruce

    2016-10-12

    DAS-40278-9 maize, which is developed by Dow AgroSciences, has been genetically modified to express the aryloxyalkanoate dioxygenase-1 (AAD-1) protein and is tolerant to phenoxy auxin herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D). To understand the metabolic route and residue distribution of 2,4-D in DAS-40278-9 maize, a metabolism study was conducted with (14)C-radiolabeled 2,4-D applied at the maximum seasonal rate. Plants were grown in boxes outdoors. Forage and mature grain, cobs, and stover were collected for analysis. The metabolism study showed that 2,4-D was metabolized to 2,4-dichlorophenol (2,4-DCP), which was then rapidly conjugated with glucose. Field-scale residue studies with 2,4-D applied at the maximum seasonal rate were conducted at 25 sites in the U.S. and Canada to measure the residues of 2,4-D and free and conjugated 2,4-DCP in mature forage, grain, and stover. Residues of 2,4-D were not detectable in the majority of the grain samples and averaged <1.0 and <1.5 μg/g in forage and stover, respectively. Free plus conjugated 2,4-DCP was not observed in grain and averaged <1.0 μg/g in forage and stover.

  4. Development of multiplex PCR method for simultaneous detection of four events of genetically modified maize: DAS-59122-7, MIR604, MON863 and MON88017.

    PubMed

    Oguchi, Taichi; Onishi, Mari; Mano, Junichi; Akiyama, Hiroshi; Teshima, Reiko; Futo, Satoshi; Furui, Satoshi; Kitta, Kazumi

    2010-01-01

    A novel multiplex PCR method was developed for simultaneous event-specific detection of four events of GM maize, i.e., DAS-59122-7, MIR604, MON88017, and MON863. The single laboratory examination of analytical performance using simulated DNA mixtures containing GM DNA at various concentrations in non-GM DNA suggested that the limits of detection (LOD) of the multiplex PCR method were 0.16% for MON863, MIR604, and MON88017, and 0.078% for DAS-59122-7. We previously developed a nonaplex (9plex) PCR method for eight events of GM maize, i.e., Bt11, Bt176, GA21, MON810, MON863, NK603, T25, and TC1507. Together with the nonaplex PCR method, the newly developed method enabled the detection and identification of eleven GM maize events that are frequently included in commercial GM seed used in Japan. In addition, this combinational analysis may be useful for the identification of combined event products of GM maize.

  5. Brazil's premier gold province. Part I: The tectonic, magmatic, and structural setting of the Archean Rio das Velhas greenstone belt, Quadrilátero Ferrífero

    NASA Astrophysics Data System (ADS)

    Lobato, Lydia; Ribeiro-Rodrigues, Luiz; Zucchetti, Márcia; Noce, Carlos; Baltazar, Orivaldo; da Silva, Luiz; Pinto, Claiton

    2001-07-01

    Rocks of the Rio das Velhas Supergroup comprise one of the most significant Archean greenstone-belt successions in Brazil, in both their appreciable mineral productivity and extensive mineral potential. A large part of this greenstone belt is contained within the Quadrilátero Ferrífero (Iron Quadrangle) region, Minas Gerais state, southeastern Brazil, which occupies the southernmost portion of the São Francisco craton. The Nova Lima Group rocks, at the base of the Rio das Velhas greenstone belt, host important orogenic gold deposits. The group contains lithological associations from bottom to top as follows: (1) mafic-ultramafic volcanic, (2) volcanic-chemical, (3) clastic-chemical, (4) volcaniclastic, and (5) resedimented rocks. Rocks of the resedimented, volcanic-chemical, and mafic-ultramafic volcanic associations mainly host the most important gold deposits. An early compressional deformation occurs in the rocks of the Rio das Velhas greenstone belt and basement gneisses, with tangential thrusting from the north to the south or southwest. Structures generated during a second, compressional deformation, encompass NW-striking thrust faults and SW-vergent, tight to isoclinal folds, inferring a general southwest transport direction. In the central portion of the Quadrilátero Ferrífero, the Paciência lineament, which strikes northwest and dips to the northeast in the south, or strikes northeast and dips to the southeast in the north, is a thrust-related, oblique ramp fault that hosts important gold deposits. The convergence of these two trends in the Nova Lima region is accommodated by roughly E-W-striking transcurrent faults, which are the most favored sites for large gold concentrations. Intracratonic extension in Late Archean to early Paleoproterozoic times and NW-vergent, Trans-Amazonian compressional deformation post-date gold deposition. Late extension during the Paleoproterozoic led to basin formation and the prominent dome-and-keel architecture of the

  6. Feeling Normal? Long-Term Follow-up of Patients with a Cleft Lip-Palate after Rhinoplasty with the Derriford Appearance Scale (DAS-59).

    PubMed

    Albers, Andreas E; Reichelt, Andreas C; Nolst-Trenité, Gilbert J; Menger, Dirk Jan

    2016-04-01

    The stigma of nasal deformity due to a congenital cleft lip-palate has an undeniable influence on the affected patient's life. It is therefore of interest to investigate if efforts to reduce esthetic and functional impairments by rhinoplasty (single or multiple) can result in an increased satisfaction with appearance and a self-perception similar to the noncleft population. Retrospective scoring before and after rhinoplasty using the validated Derriford Appearance Scale (DAS-59) and subsequent statistical evaluation and comparison to datasets available in the literature for further classification was used. Of the 61 patients who underwent at least one rhinoplasty, 26 responded to all questions. The mean age of responders was approximately 30 years of age and the male:female ratio was 1:1.2. The scale showed a significant overall improvement after surgery. The full scale and all subscale scores of the DAS-59 were significantly reduced after surgery demonstrating an improvement in the respective categories. Most importantly, if postoperative results were compared with a population concerned and unconcerned about appearance, no difference "facial self-consciousness" of appearance was apparent. Also postoperative subscores for "general self-consciousness" (GSC) and "social self-consciousness" of appearance (SSC) showed no difference from those obtained from the population concerned about appearance. The postoperative subscore for "sexual and bodily self-consciousness" of appearance (SBSC) indicated improvement beyond the level found in the concerned control population. Due to only a low improvement in the difference compared with the subscore representing a "negative self-concept," a statistically significant difference to the concerned population remained, possibly indicating that therapy beyond surgery is needed for improvement. After rhinoplasty, the investigated group of cleft lip-palate patients with nasal deformities showed an improvement in their self

  7. Registry of Hospital Das Clínicas of the University of São Paulo Medical School: First Official Solid Organ and Tissue Transplantation Report – 2008

    PubMed Central

    Azeka, Estela; Auler Júnior, José Otavio Costa; Fernandes, Paulo Manuel Pego; Nahas, Willian Carlos; Fiorelli, Alfredo Inácio; Tannuri, Uenis; Cristofani, Lílian Maria; Caiero, Marcelo Tadeu; Dulley, Frederico Luiz; de Oliveira Paggiaro, André; Bacchella, Telesforo

    2009-01-01

    OBJECTIVE: The aim of this study was to report a single center experience of organ and tissue transplantation INTRODUCTION: This is the first report of organ and tissue transplantation at the Hospital das Clínicas of the University of Sao Paulo Medical School. METHODS: We collected data from each type of organ transplantation from 2002 to 2007. The data collected were patient characteristics and actuarial survival Kaplan-Meier curves at 30 days, one year, and five years RESULTS: There were a total of 3,321 transplants at our institution and the 5-year survival curve ranged from 53% to 88%. CONCLUSION: This report shows that solid organ and tissue transplants are feasible within the institution and allow us to expect that the quality of transplantation will improve in the future. PMID:19219318

  8. Short-term monitoring of a gas seep field in the Katakolo bay (Western Greece) using Raman spectra DTS and DAS fibre-optic methods

    NASA Astrophysics Data System (ADS)

    Chalari, A.; Mondanos, M.; Finfer, D.; Christodoulou, D.; Kordella, S.; Papatheodorou, G.; Geraga, M.; Ferentinos, G.

    2012-12-01

    A wide submarine seep of thermogenic gas in the Katakolo bay, Western Greece, was monitored passively using the intelligent Distributed Acoustic Sensor (iDAS) and Ultima Raman spectra Distributed Temperature Sensor (DTS), in order to study the thermal and noise signal of the bubble plumes released from the seafloor. Katakolo is one one of the most prolific thermogenic gas seepage zones in Europe and the biggest methane seep ever reported in Greece. Very detailed repetitive offshore gas surveys, including marine remote sensing (sub-bottom profiling, side scan sonar), underwater exploration by a towed instrumented system (MEDUSA), long-term monitoring benthic station (GMM), compositional and isotopic analyses, and flux measurements of gas, showed that: (a) gas seepage takes place over an extended area in the Katakolo harbour and along two main normal faults off the harbour; (b) at least 823 gas bubble ( 10-20 cm in diameter) plumes escaping over an area of 94,200 m2, at depths ranging from 5.5 to 16 m; (c) the gas consists mainly of methane and has H2S levels of hundreds to thousands ppmv, and shows significant amounts of other light hydrocarbons like ethane, propane, iso-butane and C6 alkanes, (d) offshore and onshore seeps release the same type of thermogenic gas; (e) due to the shallow depth, more than 90 % of CH4 released at the seabed enters the atmosphere, and (f) the gas seeps may produce severe geohazards for people, buildings and construction facilities due to the explosive and toxicological properties of methane and hydrogen sulfide, respectively. For the short-term monitoring, the deployment took place on a site located inside the harbour of Katakolo within a thermogenic gas seepage area where active faults are intersected. The iDAS system makes it possible to observe the acoustical signal along the entire length of an unmodified optical cable without introducing any form of point sensors such as Bragg gratings. When the bubble plumes are released by the

  9. Dating human occupation at Toca do Serrote das Moendas, São Raimundo Nonato, Piauí-Brasil by electron spin resonance and optically stimulated luminescence.

    PubMed

    Kinoshita, Angela; Skinner, Anne R; Guidon, Niede; Ignacio, Elaine; Felice, Gisele Daltrini; Buco, Cristiane de A; Tatumi, Sonia; Yee, Márcio; Figueiredo, Ana Maria Graciano; Baffa, Oswaldo

    2014-12-01

    Excavation of Toca do Serrote das Moendas, in Piauí state, Brazil revealed a great quantity of fossil wild fauna associated with human remains. In particular, fossils of a cervid (Blastocerus dichotomus) were found, an animal frequently pictured in ancient rock wall paintings. In a well-defined stratum, two loose teeth of this species were found in close proximity to human bones. The teeth were independently dated by electron spin resonance (ESR) in two laboratories. The ages obtained for the teeth were 29 ± 3 ka (thousands of years) and 24 ± 1 ka. The concretion layer capping this stratum was dated by optically stimulated luminescence (OSL) of the quartz grains to 21 ± 3 ka. As these values were derived independently in three different laboratories, using different methods and equipment, these results are compelling evidence of early habitation in this area.

  10. Application of a Fibre Optic Distributed Acoustic Sensor (DAS) for Shallow Seismic Investigations of a Fractured Dolostone Aquifer in Guelph, Ontario.

    NASA Astrophysics Data System (ADS)

    Munn, J. D.; Parker, B. L.; Coleman, T. I.; Mondanos, M.; Chalari, A.

    2014-12-01

    Understanding groundwater flow and contaminant transport in fractured bedrock aquifers requires detailed characterization of the discrete features that control flow, as well as the properties of the rock matrix. This requires multiple, high-resolution, depth discrete datasets that provide different, but complementary information. Distributed fibre optic sensing is a relatively new technology used to continuously monitor properties along the entire length of an optical fibre. Technological advances over the past few years have brought the sensitivity and spatial resolution to the point where shallow (<200m) borehole applications are practicable. Recent studies using fibre optic distributed temperature sensors (DTS) have shown excellent application of DTS for characterizing groundwater flow in both continuously sealed and open boreholes. This presentation highlights the results of a field trial at the Bedrock Aquifer Research Station on the University of Guelph campus (Ontario, Canada) where a single fibre optic cable was interrogated by both a DTS (Ultima-DTS) and a Distributed Acoustic Sensor (iDAS). DAS is a relatively recent development that allows an optical fibre to be used as a receiver for seismic imaging. These seismic images are produced by sending an optical pulse down the fibre and analyzing the effects of seismic waves on the propagating light. Numerous vertical seismic profiles were collected and the effects of different fibre optic cable structures and coupling techniques were examined. The seismic profiles will help delineate structural features and lithological contacts away from the borehole wall, and will assist in correlating other geophysical, hydraulic, or geological logs collected in the boreholes across the site. Preliminary results show promise for shallow seismic imaging and continued field trials will allow refinement of the technique.

  11. The CluTim algorithm: an improvement on the impact parameter estimates

    NASA Astrophysics Data System (ADS)

    Chiarello, G.; Chiri, C.; Cocciolo, G.; Corvaglia, A.; Grancagnolo, F.; Miccoli, A.; Panareo, M.; Pinto, C.; Pepino, A.; Spedicato, M.; Tassielli, G. F.

    2017-03-01

    A Drift Chamber is a detector used in high energy physics experiments for determining charged particles trajectories. The signal pulses from all the wires are then collected and the particle trajectory is tracked assuming that the distances of closest approach (the impact parameter) between the particle trajectory and the wires coincide with the distance between the cluster ions generated by the particle and the wire closer to it. The widespread use of helium based gas mixtures, which produces a low ionization clusters density (12 cluster/cm in a 90/10 helium/iso-butane mixture), introduces a sensible bias in the impact parameter assumption, particularly for short impact parameters and small cell drift chambers. Recently, an alternative track reconstruction (Cluster Counting/Timing) technique has been proposed, which consists in measuring the arrival times on the wires of each individual ionization cluster and combining these times to get a bias free estimate of the impact parameter. However, in order to efficiently exploiting the cluster timing technique, it is necessary to have read-out interfaces capable of processing a large quantity of high speed signals. We describe the design of a read-out board capable of acquiring the information coming from a fast digitization of the signals generated in a drift chamber and the algorithm for identifying the individual ionization pulse peaks and recording their time and amplitude.

  12. APPLICATION OF MULTI-DATE LANDSAT 5 TIM IMAGERY FOR WETLAND IDENTIFICATION

    EPA Science Inventory

    Multi-temporal Landsat 5 Thematic Mapper (TM) imagery was evaluated for the identification and monitoring of potential jurisdictional wetlands located in the states of Maryland and Delaware. A wetland map prepared from single-date TM imagery was compared to a hybrid map develope...

  13. Stimulated zonal flow generation in the case of TEM and TIM microturbulence

    NASA Astrophysics Data System (ADS)

    Gravier, E.; Lesur, M.; Reveille, T.; Drouot, T.

    2016-09-01

    In this paper, we show that in some parameter range in gyrokinetic simulations, it is possible to apply a control method to stimulate the appearance of zonal flows while minimizing the duration of the control process and the impact on plasma parameters. For this purpose, a gyrokinetic code considering only trapped particles is used. The starting point of our work is a situation where zonal flows transiently appear after the nonlinear phase of saturation of trapped electron modes or trapped ion modes' micro-instabilities. These are observed to be strongly reduced in a later phase, permitting streamers to govern the plasma behavior in the steady-state. By intervening during this latter state (after this transient growth and decay of zonal flow), i.e., by increasing the ion/electron temperature ratio for a short time, it is found to be possible to bifurcate to a new steady-state, in which zonal flows are strongly present and are maintained indefinitely, thereby allowing a significant reduction in radial heat fluxes.

  14. Teaching Identity Performance through Tim O'Brien's "The Things They Carried"

    ERIC Educational Resources Information Center

    Gratch, Ariel

    2015-01-01

    People express part of their identity through their style, gestures, speech patterns, and language use. Other people read these displays as presentations of ourself, an insight into who we are. It is important, therefore, for students to recognize their own performance of identity and be able to express that identity in a clear way. By focusing on…

  15. Single Chondrule K/Ar ages of Mexican Meteorites Using ID-TIMS.

    NASA Astrophysics Data System (ADS)

    Hernandez, M.; Sole, J.

    2007-05-01

    We have determined the K/Ar ages of two H5 ordinary meteorites: Cosina and Nuevo Mercurio, neither dated until this study. We analyzed several single chondrules - weighing few milligrams - of each meteorite. Ages were obtained by using very precise K content determined by isotope dilution mass spectrometry. The K content in chondrules ranges between 650 and 1400 ppm. The 40Ar was measured by static vacuum noble gas mass spectrometry. Samples were fused with an infrared CO2 laser. Chondrule ages vary from 3.66 to 4.59 Ga for Cosina and from 4.20 to 4.87 Ga for Nuevo Mercurio. A comparison between our data and the published K/Ar ages of H and L whole rocks shows that dates obtained from single chondrules are older than those obtained from whole rocks and seem to preserve older events not evidenced in the WR ages. This implies that chondrules can preserve K/Ar ages very close to U-Pb crystallization ages.

  16. 1973 Winter Simulation Conference. Sponsored by ACM/AIIE/SHARE/SCi/TIMS.

    ERIC Educational Resources Information Center

    Hoggatt, Austin Curwood, Ed.

    A record of the current state of the art of simulation and the major part it now plays in policy formation in large organizations is provided by these conference proceedings. The 40 papers presented reveal an emphasis on the applications of simulation. In addition, the abstracts of 28 papers submitted to a more informal "paper fair" are also…

  17. Emeishan volcanism and the end-Guadalupian extinction: New U-Pb TIMS ages

    NASA Astrophysics Data System (ADS)

    Mundil, Roland; Denyszyn, Steve; He, Bin; Metcalfe, Ian; Yigang, Xu

    2010-05-01

    High-resolution geochronology with an age resolution at the permil level is instrumental in testing proposed causal links between continental-scale, short-term volcanic events and environmental crises that affect life globally. Synchroneity with large-scale volcanic events has been shown for three of the five most severe extinctions, namely the end-Permian extinction coinciding with Siberian Trapp volcanism, the end-Triassic extinction with Central Atlantic Magmatic Province) volcanism and the end-Cretaceous with Deccan Trapp volcanism. Recent studies also show that the magnitude of the extinction is not solely a function of the size (volume) of the volcanic event but more importantly of the eruption rate and also the nature of the host rock that is intruded, and the resulting reactions and release of gases that can affect climate. The end-Guadalupian (end Middle Permian, ca 260 Ma) biotic crisis has traditionally not been included in the 'big five' mass extinctions, possibly because of its close proximity in time to the end-Permian event, although its magnitude (in terms of total extinction rate) is comparable to the three most severe extinctions (end-Ordovician, end-Permian, end-Cretaceous). As a result, research of the end-Guadalupian event has so far been neglected and its timing as well as the temporal relation to the Emeishan volcanic province in western China is as yet not fully studied. Geochronological data are so far mostly based on ambiguous 40Ar/39Ar analyses of commonly altered basaltic products and U-Pb zircon analyses on felsic products using micro-beam techniques that typically result in radio-isotopic ages with percent-level uncertainty, and thus insufficient for high-resolution correlations of events. In addition, no precise and accurate radio-isotopic data exist from this time period so that evolutionary events (extinction and recovery) on land and in the ocean are notoriously difficult to correlate though biostratigraphic records are available from numerous sedimentary archives. A further complication arises from the severe tectonic (and resulting thermal) overprint, due to the closure of the Tethys and the collision of the Indian plate with Asia, of most of the area where Emeishan volcanic products are exposed. Also, currently existing paleo-environmental data are scarce and insufficient for testing this hypothesis with confidence, because studies using stable isotopes as proxies are restricted to short profiles from only a few sites. Therefore, fundamental questions remain unanswered. We present new data U-Pb IDTIMS ages with permil-level resolution that constrain the timing of Emeishan volcanism and the timing of biotic events recorded in sediments. In detail, U-Pb results are from felsic intercalations within late stage Emeishan products and biostratigaphically calibrated marine sedimentary sections in southwestern and central China as well as thick tuffs within terrestrial sections from the Bowen Basin in eastern Australia. There is also great potential for obtaining precise U-Pb age results on volcanic products with basaltic composition using the accessory mineral baddeleyite the occurrence of which we have already confirmed. Geochronological and geochemical research is complemented with paleo-enviromental studies and biostratigraphy. We expect that through integration of U-Pb and 40Ar/39Ar geochronology with chemo- and biostratigraphy, the time scale of the Middle through Late Permian will be greatly improved and will lead to a more realistic evaluation of potential causes for the biotic crisis and its aftermath.

  18. The Story of Tim: A Descriptive Study of Placement Procedures in Rural Supported Employment.

    ERIC Educational Resources Information Center

    Martin, Christie R.; Elrod, G. Franklin

    1989-01-01

    Describes the processes by which an educable mentally retarded high school student was placed and trained to work in a family-operated dairy. Outlines the task analysis procedure used by his job coach during five weeks of training. (SV)

  19. NASA Technical Interchange Meeting (TIM): Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box

    NASA Technical Reports Server (NTRS)

    ONeil, D. A.; Craig, D. A.; Christensen, C. B.; Gresham, E. C.

    2005-01-01

    The objective of this Technical Interchange Meeting was to increase the quantity and quality of technical, cost, and programmatic data used to model the impact of investing in different technologies. The focus of this meeting was the Technology Tool Box (TTB), a database of performance, operations, and programmatic parameters provided by technologists and used by systems engineers. The TTB is the data repository used by a system of models known as the Advanced Technology Lifecycle Analysis System (ATLAS). This report describes the result of the November meeting, and also provides background information on ATLAS and the TTB.

  20. Simultaneous functions of the installed DAS/DAK formaldehyde-assimilation pathway and the original formaldehyde metabolic pathways enhance the ability of transgenic geranium to purify gaseous formaldehyde polluted environment.

    PubMed

    Zhou, Shengen; Xiao, Sunqin; Xuan, Xiuxia; Sun, Zhen; Li, Kunzhi; Chen, Limei

    2015-04-01

    The overexpression of dihydroxyacetone synthase (DAS) and dihydroxyacetone kinase (DAK) from methylotrophic yeasts in chloroplasts created a photosynthetic formaldehyde (HCHO)-assimilation pathway (DAS/DAK pathway) in transgenic tobacco. Geranium has abilities to absorb and metabolize HCHO. Results of this study showed that the installed DAS/DAK pathway functioning in chloroplasts greatly enhanced the role of the Calvin cycle in transgenic geranium under high concentrations of gaseous HCHO stress. Consequently, the yield of sugars from HCHO-assimilation increased approximately 6-fold in transgenic geranium leaves, and concomitantly, the role of three original HCHO metabolic pathways reduced, leading to a significant decrease in formic acid, citrate and glycine production from HCHO metabolism. Although the role of three metabolic pathways reduced in transgenic plants under high concentrations of gaseous HCHO stress, the installed DAS/DAK pathway could still function together with the original HCHO metabolic pathways. Consequently, the gaseous HCHO-resistance of transgenic plants was significantly improved, and the generation of H2O2 in the transgenic geranium leaves was significantly less than that in the wild type (WT) leaves. Under environmental-polluted gaseous HCHO stress for a long duration, the stomata conductance of transgenic plants remained approximately 2-fold higher than that of the WT, thereby increasing its ability to purify gaseous HCHO polluted environment.

  1. Further evidence of 777 Ma subduction-related continental arc magmatism in Eastern Dom Feliciano Belt, southern Brazil: The Chácara das Pedras Orthogneiss

    NASA Astrophysics Data System (ADS)

    Koester, E.; Porcher, C. C.; Pimentel, M. M.; Fernandes, L. A. D.; Vignol-Lelarge, M. L.; Oliveira, L. D.; Ramos, R. C.

    2016-07-01

    In this study new SHRIMP U-Pb zircon data for the Chácara das Pedras Gneiss in Porto Alegre, southern Brazil are presented. They represent a small exposure of the crust which was intruded by a large volume of orogenic to anorogenic granitoids at ca. 618-562 m.y. in the Eastern Domain of the Dom Feliciano Belt. The Chácara das Pedras tonalitic orthogneiss has geochemical similarities with subduction-related magmatic rocks of continental arcs. They present high Sr initial ratios (∼0.712), negative ɛNd(t = 777) values (∼-6), TDM varying from 1.8 to 2.0 Ga. The igneous protoliths of these orthogneisses were previously considered to be Paleoproterozoic based on an upper intercept age of discordant zircon analyses. In the present study these orthogneisses were re-sampled and re-analyzed in an attempt to obtain more concordant analytical data. The U-Pb zircon analyses were carried out using the SHRIMP IIe at the Laboratório de Geocronologia de Alta Resolução of the Universidade de São Paulo. The U-Pb concordia age obtained for igneous textural domains of the zircon grains is 777 ± 4 Ma. A few analyses on zircon overgrowths give poorly defined late Cryogenian ages of ca. 650 Ma. Older ages, mostly discordant, were obtained in a few zircon cores, showing an upper intercept age of ca. 1.9 Ga. One sample of the Três Figueiras Granodiorite, which crosscut the orthogneiss in the same outcrop, was also investigated. The zircons of this granodiorite are, however, mostly metamitic, preventing the determination of a reliable age. Some concordant analyses from a few grains define ages ranging in the interval between ca. 603 and 1022 Ma. The youngest (ca. 603 Ma) may represent a maximum age for the granodiorite crystallization. Older ages, with discordance <10%, are of 745, 777, 836 and 1022 Ma. The 777 ± 4 Ma age obtained for the Chácara das Pedras orthogneiss is the first Early Cryogenian magmatic age determined for granitoids in the Porto Alegre region, although

  2. Massa do gás e das estrelas em aglomerados: eficiência da formação estelar

    NASA Astrophysics Data System (ADS)

    Laganá, T. F.; Lima Neto, G. B.

    2003-08-01

    Os aglomerados de galáxias apresentam um interesse especial para a cosmologia observacional. Eles são as maiores estruturas ligadas pela gravitação no Universo e relaxadas na região central. A comparação entre a massa do gás intra-aglomerado (responsável por ~25% da massa total, inferida a partir de observações em raios-X), a massa contida nas estrelas (i.e., nas galáxias) e a massa total (incluindo a matéria escura não bariônica), nos dá informações importantes sobre os processos de formação e evolução de aglomerados. Por exemplo, a razão entre a massa do gás e a massa total é uma medida da fração de bárions no Universo (razão entre a matéria bariônica e matéria escura) e, utilizando a densidade de bárions predita pela nucleosíntese primordial, podemos deduzir a densidade de matéria escura no Universo (cf. White et al. 1993). O objetivo deste trabalho é obter as razões entre as massas do gás, estelar (contida nas galáxias), e a total (massa dinâmica). As massas do gás e total são obtidas a partir das análises fotométrica e espectroscópica em raios-X enquanto que a massa estelar é obtida pela análise fotométrica das galáxias. Esta análise foi aplicada ao aglomerado Abell 496 observado pelo satélite XMM-Newton. A massa contida nas galáxias foi estimada a partir da função de luminosidade obtida por Durret et al. (2002). Para determinar as massas dinâmica e do gás nos precisamos determinar os perfis radiais de densidade e temperatura. Nós apresentaremos aqui estes resultados e suas implicações na eficiência da formação estelar em Abell 496.

  3. [Nutritional status of patients with breast cancer attended in the Mastology Service of Belo Horizonte's Hospital das Clínicas in the state of Minas Gerais, Brazil].

    PubMed

    de Oliveira, Dirce Ribeiro; Carvalho, Erika Simone Coelho; Campos, Liliane Cunha; Leal, José Adalberto; Sampaio, Estela Viana; Cassali, Geovanni Dantas

    2014-05-01

    The scope of this article is to evaluate the nutritional status, body composition and tumor characteristics of 31 patients with breast cancer attended at the Mastology Service of Hospital das Clínicas of the Federal University of Minas Gerais. Dietary data were obtained from the 24-hour dietary recall in the pre-operative state and analyzed by the DietWin Professional 2008 Nutrition Software. Body composition was assessed by bioelectrical impedance analysis. The tumor characterization data were collected from medical records. The mean age of patients was 50.75 ± 14.34 years. Excess body weight was found in 58% and waist circumference greater than 80 cm in 64.5% of patients Excessive consumption of oils and sugars was observed in 90.3% and 83.8%, respectively. Most had low intakes of calcium and vitamins B6, B12 and A. The predominant diagnosis was type II histological grade invasive ductal carcinoma in stage II or III. The prevalence of overweight and inadequate dietary intake demonstrate the need for individualized nutritional guidance and monitoring to improve the prognosis and quality of the life of patients.

  4. [Travelers' vaccinations: experience from the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine].

    PubMed

    Chinwa Lo, Simone; Mascheretti, Melissa; Chaves, Tânia do Socorro Souza; Lopes, Marta Heloisa

    2008-01-01

    The profile and vaccination status of travelers seeking pre-travel medical advice at the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine, and the vaccines recommended for them, were analyzed in the present study. Among the 445 travelers who were studied, 51% were women, the median age was 33.5 years, 51% were traveling on business and 39.5% were traveling for leisure purposes. The destinations most sought were Africa (47%), Asia (31.7%) and South America (21.4%). Vaccination before traveling was recommended for 385 (86.5%) of the travelers. The main vaccines recommended were against typhoid fever (55.7%), diphtheria-tetanus (54.1%), hepatitis A (46.1%), hepatitis B (44.2%) and yellow fever (24.7%). The pre-travel guidance was shown to be important not only for indicating the vaccines recommended for the trip, but also as an opportunity to update routine vaccinations.

  5. Dating of fossil human teeth and shells from Toca do Enoque site at Serra das Confusões National Park, Brazil.

    PubMed

    Kinoshita, Angela; Sullasi, Henry L; Asfora, Viviane K; Azevedo, Renata L; Guzzo, Pedro; Guidon, Niede; Figueiredo, Ana Maria G; Khoury, Helen; Pessis, Anne-Marie; Baffa, Oswaldo

    2016-06-07

    This work reports the dating of a fossil human tooth and shell found at the archaeological site Toca do Enoque located in Serra das Confusões National Park (Piauí, Brazil). Many prehistoric paintings have been found at this site. An archaeological excavation unearthed three sepulchers with human skeletons and some shells. Two Brazilian laboratories, in Ribeirão Preto (USP) and Recife (UFPE), independently performed Electron Spin Resonance (ESR) measurements to date the tooth and the shell and obtain the equivalent dose received by each sample. The laboratories determined similar ages for the tooth and the shell (~4.8 kyBP). The results agreed with C-14 dating of the shell and other samples (charcoal) collected in the same sepulcher. Therefore, this work provides a valid inter-comparison of results by two independent ESR-dating laboratories and between two dating methods; i.e., C-14 and ESR, showing the validity of ESR dating for this range of ages.

  6. [Voice disorder clinic in the speech therapy outpatient unit at "Hospital das Clínicas da Universidade Federal de Minas Gerais"].

    PubMed

    Menezes, Letícia Neiva de; Behlau, Mara; Gama, Ana Cristina Côrtes; Teixeira, Letícia Caldas

    2011-07-01

    This study set out to describe the profile of the patients with voice complaints and/or alterations who were attended between July 2003 and December 2006 at the speech therapy outpatient unit of "Hospital das Clínicas da Universidade Federal de Minas Gerais." This was analyzed according to age, sex, profession, schooling, origin, treatment performed and factors that interfere in medical care evolution. This was a retrospective study based on the analysis of the recorded data of the individuals according to a specifically prepared Protocol. The results showed that the individuals included in this study were predominantly young women, referred by a specialist from Belo Horizonte, who do not work and also have incomplete elementary school education. Attendance of those patients was on an individual basis, and almost half of them were discharged by the speech therapist. The elderly patients, who have functional or psychogenic dysphonia and a neutral or wheezy type of voice, showed a close correlation with the discharge rate by speech therapist. The younger individuals with organo-functional dysphonia bore a statistical correlation with abandoning treatment. The individuals who eventually abandoned treatment did not bear any correlation with the crossed variables.

  7. Cometas: Das Lendas aos Fatos

    NASA Astrophysics Data System (ADS)

    Voelzke, M. R.

    O descobrimento de cometas, devido ao seu aparecimento espetacular, tem registro nas mais antigas culturas humanas. A primeira referência situa-se no ano de 1095 antes de Cristo [a.C.; HO; HO, 1962]. A quantidade de registros de descobrimentos cometários, principalmente provenientes do território chinês em particular e do oriente em geral, aumentou gradualmente a partir do quarto século depois de Cristo (d.C.). É de origem chinesa a primeira referência ao cometa P/Halley no ano de 240 a.C. [VOELZKE, 1993]. Com o desenvolvimento da astronomia relativamente às técnicas observacionais os descobrimentos bem como as observações cometárias aumentaram sensivelmente a partir do século XVII, sendo que a partir do século XIX um novo incremento ocorreu devido ao emprego da fotografia e a resultante melhora de sensibilidade na observação.

  8. The geology of the Morro Velho gold deposit in the Archean Rio das Velhas greenstone belt, Quadrilátero Ferrífero, Brazil

    USGS Publications Warehouse

    Vial, Diogenes Scipioni; DeWitt, Ed; Lobato, Lydia Maria; Thorman, Charles H.

    2007-01-01

    The Morro Velho gold deposit, Quadrilátero Ferrífero region, Minas Gerais, Brazil, is hosted by rocks at the base of the Archean Rio das Velhas greenstone belt. The deposit occurs within a thick carbonaceous phyllite package, containing intercalations of felsic and intermediate volcaniclastic rocks and dolomites. Considering the temporal and spatial association of the deposit with the Rio das Velhas orogeny, and location in close proximity to a major NNW-trending fault zone, it can be classified as an orogenic gold deposit. Hydrothermal activity was characterized by intense enrichment in alteration zones of carbonates, sulfides, chlorite, white mica±biotite, albite and quartz, as described in other Archean lode-type gold ores. Two types of ore occur in the deposit: dark gray quartz veins and sulfide-rich gold orebodies. The sulfide-rich orebodies range from disseminated concentrations of sulfide minerals to massive sulfide bodies. The sulfide assemblage comprises (by volume), on average, 74% pyrrhotite, 17% arsenopyrite, 8% pyrite and 1% chalcopyrite. The orebodies have a long axis parallel to the local stretching lineation, with continuity down the plunge of fold axis for at least 4.8 km. The group of rocks hosting the Morro Velho gold mineralization is locally referred to as lapa seca. These were isoclinally folded and metamorphosed prior to gold mineralization. The lapa seca and the orebodies it hosts are distributed in five main tight folds related to F1 (the best examples are the X, Main and South orebodies, in level 25), which are disrupted by NE- to E-striking shear zones. Textural features indicate that the sulfide mineralization postdated regional peak metamorphism, and that the massive sulfide ore has subsequently been neither metamorphosed nor deformed. Lead isotope ratios indicate a model age of 2.82 ± 0.05 Ga for both sulfide and gold mineralization. The lapa seca are interpreted as the results of a pre-gold alteration process and may be

  9. Guidelines on management of human infection with the novel virus influenza A (H1N1)--a report from the Hospital das Clínicas of the University of São Paulo.

    PubMed

    Hajjar, Ludhmila Abrahao; Schout, Denise; Galas, Filomena Regina Barbosa Gomes; Uip, David Everson; Levin, Anna Sara Shafferman; Caiaffa Filho, Helio Hehl; Sakane, Pedro Takanori; Suslik, Carlos Alberto; Teixeira, Jose Manoel de Camargo; Bonfa, Eloisa; Barone, Antonio Alci; Martins, Milton de Arruda; Boulos, Marcos; Auler, Jose Otavio Costa

    2009-01-01

    The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July, 2009. Since then, 9.249 cases were confirmed in Brazil, most of them concentrated in São Paulo. The Hospital das Clínicas of the University of São Paulo is a reference center for H1N1 cases in São Paulo. The purpose of this review is to analyze the evidence concerning diagnosis, prevention, and treatment of novel influenza A (H1N1) infection. In addition, we propose guidelines for the management of this pandemic emphasizing Hospital das Clínicas "bundles" for the control of the pandemic novel influenza A (H1N1).

  10. Using the DAS-ELISA Test to Establish an Effective Distance Between Bait Stations for Control of Linepithema humile (Hymenoptera: Formicidae) in Natural Areas.

    PubMed

    Song, Jinbo; Benson, Eric P; Zungoli, Patricia A; Gerard, Patrick; Scott, Simon W

    2015-08-01

    Linepithema humile (Mayr), the Argentine ant, is an invasive pest that has spread throughout the United States and is a problem in natural and managed habitats in South Carolina. Foraging patterns and the effectiveness of liquid baits for control of this pest have been studied in urban areas. However, similar studies have not been conducted in natural areas such as parks, picnic grounds, or campsites. L. humile populations can be large and widespread, making them a major nuisance pest for visitors to these natural areas. The primary objective of this study was to determine an effective distance between bait stations for control of L. humile in a natural area. A double antibody-sandwich enzyme-linked immunosorbent assay (DAS-ELISA) procedure was used to detect individual ants that consumed rabbit immunoglobin (IgG) protein for marking and tracking. In both lab and field conditions, there was a significant difference in the detection of IgG in ants fed protein marker mixed with sugar water compared with ants only fed sugar water. Additional field studies revealed that an individual ant could retain detectable levels of protein marker for 3 d and that an ant feeding on IgG containing bait could be detected over 15 m from the original bait source. Overall, we found that using liquid ant baits, with a placement of 20 m between stations, was effective in reducing L. humile numbers between April to October, 2012 in a natural park area of Lake Greenwood State Park, SC.

  11. Brazil's premier gold province. Part II: geology and genesis of gold deposits in the Archean Rio das Velhas greenstone belt, Quadrilátero Ferrífero

    NASA Astrophysics Data System (ADS)

    Lobato, Lydia; Ribeiro-Rodrigues, Luiz; Vieira, Frederico

    2001-07-01

    Orogenic, gold deposits are hosted by rocks of the Archean Rio das Velhas greenstone belt in the Quadrilátero Ferrífero region, Minas Gerais state, Brazil, one of the major gold provinces in the world. The gold deposits occur at the base of the mafic-ultramafic succession, with the most important orebodies controlled by E-W-striking, strike-slip faults. The main mineralization styles are (1) structurally controlled, sulfide replacement zones in banded iron formation (BIF); (2) disseminated sulfide minerals and gold in hydrothermally altered rocks along shear zones; and (3) auriferous quartz-carbonate-sulfide veins and veinlets in mafic, ultramafic, and felsic volcanic rocks, and also in clastic sedimentary rocks. The most common host rocks for ore are metamorphosed oxide- and carbonate-facies banded iron (± iron-rich metachert) formations (e.g., the Cuiabá, São Bento and Raposos deposits) and the lapa seca unit, which is a local term for intensely carbonatized rock (e.g., the giant Morro Velho mine with >450 t of contained gold). Metabasalts host most of the remaining gold deposits. Mineralogical characteristics and fluid inclusion studies suggest variations in the H2O/CO2 ratio of a low-salinity, near-neutral, reducing, sulfur-bearing, ore fluid. The presence of abundant CH4-rich inclusions is related to reduction of the original H2O-CO2 fluid via interaction with carbonaceous matter in the wallrocks. Oxygen fugacity was close to that of graphite saturation, with variations likely to have been influenced by reaction with the carbonaceous matter. Carbon-rich phyllites and schists, which commonly bound ore-bearing horizons, seem to have played both a physical and chemical role in localizing hydrothermal mineral deposition. Microtextural studies indicate that gold deposition was mainly related to desulfidation reactions, and was paragenetically coeval with precipitation of arsenic-rich iron sulfide minerals. Carbon isotope data are compatible with dissolution of

  12. Epidemiology of human infection with the novel virus influenza A (H1N1) in the Hospital das Clínicas, São Paulo, Brazil--June-September 2009.

    PubMed

    Schout, Denise; Hajjar, Ludhmila Abrahao; Galas, Filomena Regina Barbosa Gomes; Uip, David Everson; Levin, Anna Sara Shafferman; Caiaffa Filho, Helio Hehl; Sakane, Pedro Takanori; Suslik, Carlos Alberto; Teixeira, Jose Manoel de Camargo; Bonfa, Eloisa; Barone, Antonio Alci; Martins, Milton de Arruda; Boulos, Marcos; Auler, Jose Otavio Costa

    2009-01-01

    The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July 16, 2009. Since then, 46,810 cases of acute respiratory syndrome have been reported in Brazil, most of them concentrated in São Paulo. Through September 16, we have confirmed 9,249 cases of novel influenza A H1N1in Brazil, including 699 deaths. The mortality rate observed in Brazil is 0.47/100,000 inhabitants and varies according to region. In this period, São Paulo registered 3733 cases (40.3% of the total) of novel influenza A (H1N1) infection and 327 deaths, reflecting a mortality rate of 0.79/100,000 inhabitants. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC) is a reference center for H1N1 cases in São Paulo. During the winter of 2009, 472 patients in this hospital were diagnosed with H1N1 infection; of these, 210 were admitted, and 16 died. To control this pandemic and to provide adequate care for these patients, the Hospital das Clínicas implemented "bundles" including prevention strategies, an epidemiologic surveillance service, availability of fast diagnosis, antiviral treatment and training of staff. The purpose of this manuscript is to describe the epidemiologic features of novel human influenza A (H1N1) infection in the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the winter period of the 2009 pandemic.

  13. Método numérico das diferenças finitas no domínio do tempo aplicado a ondas Alfvén em plasma astrofísico

    NASA Astrophysics Data System (ADS)

    Dos Santos, L. C.; Kintopp, J. A.; Jatenco-Pereira, V.; Opher, R.

    2003-08-01

    Ondas Alfvén em plasma astrofísico têm sido objeto de intenso estudo nas últimas décadas pelo fato de apresentarem papel importante em muitas áreas de pesquisa na astrofísica. Particularmente são importantes no mecanismo de aquecimento da coroa solar; em ventos estelares; em jatos galácticos e extragalácticos; em discos protoestelares, etc. A formulação para diferenças finitas no domínio do tempo (FDTD), aplicada a plasma magnetizado é desenvolvida para estudo das propriedades de ondas Alfvén em três dimensões (3D-FDTD). O método é aplicado inicialmente a um plasma homogêneo e isotérmico imerso em uma região com campo magnético externo B0, que sofre uma pequena perturbação. Uma vez gerada a onda, esta perturbação é retirada e, então analisamos a evolução temporal das ondas, bem como a forma de seu amortecimento.

  14. U-Pb ID-TIMS zircon ages of TTG gneisses of the Aravalli Craton of India

    NASA Astrophysics Data System (ADS)

    Chauhan, Hiredya; Saikia, Ashima; Kaulina, Tatiana; Bayanova, Tamara; Ahmad, Talat

    2015-04-01

    The crystalline basement of the Aravalli Craton is a heterogeneous assemblage dominated by granitic gneisses and granites with sporadic occurrences of amphibolites and dismembered sedimentary enclaves (Upadhyaya et al., 1992). This assemblage is known to have experienced multiple deformation and metamorphic events followed by emplacement of voluminous granites and basaltic dykes. Based on Sm-Nd whole rock data on the basement Mewar orthogneisses of Jhamarkotra region (Gopalan et al., 1990) and Pb/Pb ages of zircon from Gingla Granites which intrudes the basement (Wiedenbeck et al., 1996), it has been inferred that the whole magmatic episode leading to the formation of the basement spanned from 3300 to 2400 Ma and that the Aravalli cratonic block had broadly stabilized by 2500 Ma on which the younger Aravalli and Delhi Supergroup unconformably deposited. However, no comprehensive age data on the basement gneisses from the study area spanning the entire magmatic episode is available. This work attempts to provide a time frame work for evolution of the basement gneisses of the Aravalli Craton. We present here U-Pb zircon ages from the Precambrian basement TTG gneisses of the Aravalli Craton of north western India. Pb and U were measured on multicollector Finnigan-MAT 262 mass spectrometer. The temperatures of measurements were 1300°C for Pb and 1500°C for U. Pb isotope ratios were corrected for mass fractionation with a factor of 0.10% per amu, based on repeat analyses of the standard NBS SRM 982. The U analyses were corrected for mass fractionation with a factor of 0.003% per amu, based on repeat analyses of the NBS U 500 standard. Reproducibility of the U-Pb ratios was determined from the repeated analysis of standard zircon IGFM-87 (Ukraine) and taken as 0.5% for 207Pb/235U and 206Pb/238U ratios, respectively, at 95% confidence level. All calculations were done using the programs PBDAT and ISOPLOT (Ludwig 1991, 2008). Four zircon fractions corresponding to four zircon types from UD-16 sample yield a U-Pb discordant age of 2680±30 Ma. Two zircon fractions from UD-17 sample show discordant 207Pb/206Pb ages of 2506 and 2577 Ma. Zircons in our samples have moderate to high U contents (180-770 ppm) with low Th/U ratios (0.2-0.5) in the sample UD-16, characteristic for magmatic zircons from TTG rocks. Thus the obtained age of 2680±30 Ma is interpreted as an age of magmatic crystallization of tonalites. Gopalan, K. et al., (1990): Precambrian Res., 48, 287-297. Ludwig, K.R. (1991): PBDAT program. US. Geol. Surv. Open-file report 88-542, 38 p. Ludwig, K. R. (2008): Isoplot/Ex, version 3.6, Berkeley Geochronology Center, Special Publication no. 4. Upadhyaya, R. et al., (1992): Current Sci., 62(2): 87-92. Wiedenbeck, M. et al., (1996): Chem Geol. 129: 325-340.

  15. The Arctic Predictability and Prediction on Seasonal-to-Interannual TimEscales (APPOSITE) data set version 1

    NASA Astrophysics Data System (ADS)

    Day, Jonathan J.; Tietsche, Steffen; Collins, Mat; Goessling, Helge F.; Guemas, Virginie; Guillory, Anabelle; Hurlin, William J.; Ishii, Masayoshi; Keeley, Sarah P. E.; Matei, Daniela; Msadek, Rym; Sigmond, Michael; Tatebe, Hiroaki; Hawkins, Ed

    2016-06-01

    Recent decades have seen significant developments in climate prediction capabilities at seasonal-to-interannual timescales. However, until recently the potential of such systems to predict Arctic climate had rarely been assessed. This paper describes a multi-model predictability experiment which was run as part of the Arctic Predictability and Prediction On Seasonal to Interannual Timescales (APPOSITE) project. The main goal of APPOSITE was to quantify the timescales on which Arctic climate is predictable. In order to achieve this, a coordinated set of idealised initial-value predictability experiments, with seven general circulation models, was conducted. This was the first model intercomparison project designed to quantify the predictability of Arctic climate on seasonal to interannual timescales. Here we present a description of the archived data set (which is available at the British Atmospheric Data Centre), an assessment of Arctic sea ice extent and volume predictability estimates in these models, and an investigation into to what extent predictability is dependent on the initial state. The inclusion of additional models expands the range of sea ice volume and extent predictability estimates, demonstrating that there is model diversity in the potential to make seasonal-to-interannual timescale predictions. We also investigate whether sea ice forecasts started from extreme high and low sea ice initial states exhibit higher levels of potential predictability than forecasts started from close to the models' mean state, and find that the result depends on the metric. Although designed to address Arctic predictability, we describe the archived data here so that others can use this data set to assess the predictability of other regions and modes of climate variability on these timescales, such as the El Niño-Southern Oscillation.

  16. The Virtual Consortium: Tim Bucknall Describes How a Group of Carolina Libraries Came Together to Expand Dramatically Their Journal Content

    ERIC Educational Resources Information Center

    Bucknall, Tim

    2005-01-01

    The Carolina Consortium came into being for one purpose: to conclude deals that would allow the sharing of both the costs and the content of a large number of academic journals from three major publishers--Wiley, Springer, and Blackwell. In just a few months--and without any central authority, funding, or administrative overhead--librarians from…

  17. Boiling eXperiment Facility (BXF) Fluid Toxicity Technical Interchange Meeting (TIM) with the Payload Safety Review Panel (PSRP)

    NASA Technical Reports Server (NTRS)

    Sheredy, William A.

    2012-01-01

    A Technical Interchange meeting was held between the payload developers for the Boiling eXperiment Facility (BXF) and the NASA Safety Review Panel concerning operational anomaly that resulted in overheating one of the fluid heaters, shorted a 24VDC power supply and generated Perfluoroisobutylene (PFiB) from Perfluorohexane.

  18. T.I.M.S: TaqMan Information Management System, tools to organize data flow in a genotyping laboratory

    PubMed Central

    Monnier, Stéphanie; Cox, David G; Albion, Tim; Canzian, Federico

    2005-01-01

    Background Single Nucleotide Polymorphism (SNP) genotyping is a major activity in biomedical research. The Taqman technology is one of the most commonly used approaches. It produces large amounts of data that are difficult to process by hand. Laboratories not equipped with a Laboratory Information Management System (LIMS) need tools to organize the data flow. Results We propose a package of Visual Basic programs focused on sample management and on the parsing of input and output TaqMan files. The code is written in Visual Basic, embedded in the Microsoft Office package, and it allows anyone to have access to those tools, without any programming skills and with basic computer requirements. Conclusion We have created useful tools focused on management of TaqMan genotyping data, a critical issue in genotyping laboratories whithout a more sophisticated and expensive system, such as a LIMS. PMID:16221298

  19. Evaluation of the relative risk to birds of alternative pesticides using EPA’s TIM/MCnest Model

    EPA Science Inventory

    Agricultural producers today have many choices of active ingredients for crop protection. These products come with different active ingredients, different modes of action, and that initiate different adverse outcome pathways. Use patterns also differ considerably among products...

  20. TIMS U-series dating and stable isotopes of the last interglacial event in Papua New Guinea

    SciTech Connect

    Stein, M.; Wasserburg, G.J.; Chen, J.H. ); Aharon, P. ); Zhu, Z.R.; Chappell, J. ); Bloom, A. )

    1993-06-01

    The extensive flight of uplifted reef terraces which occurs along the Vitiaz strait on the northern flank of the Huon Peninsula in PNG (Papua New Guinea) contains a particularly good record of sea level changes in the last 250 ky. The Huon terraces were the target of an international expedition which took place in July--August 1988. In particular, the authors searched for suitable samples for U-series dating in a reef complex designated as VII, which is correlated with the last interglacial episode and high sea level stand. This complex is composed of a barrier reef (VIIb), a lagoon, and a fringing reef (VIIa). Twelve corals from these terraces and two corals from the older reef complex VIII were selected for analysis. The petrography, oxygen and carbon isotope compositions, and magnesium and strontium concentrations were determined along with the concentrations and isotopic compositions of uranium and thorium. The simplest model for sea level height for terrace VII is a continuous rise between 134 and 118 ky. Alternatively, there may have been two periods of rapid sea level rise. In contrast, in the Bahamas, there is evidence that sea level remained rather constant over the time interval 132 to 120 ky. The absence of ages between 132 and 120 ky in PNG could be the result of changes in the local tectonic uplift rates during that time, or erosion that disrupted the continuous record. In any event, the authors find no basis for accepting a single brief time for the age of the last interglacial and applying this age as a precise chronometer for worldwide correlation, or as a test of climatic models. The older ages reported here precede the Milankovitch solar insolation peak at 128 ky, and the younger ages are [approximately]10 ky after this peak. If the present high-precision data are correct, then it will be necessary to reassess the validity of the Milankovitch theory of climatic changes. 76 refs., 6 figs., 6 tabs.