Sample records for cell line rm

  1. Lectin histochemistry of the rat lymph node: visualisation of stroma, blood vessels, sinuses, and macrophages. A contribution to the concept of an immune accessory role of sinus-lining endothelia.

    PubMed

    Düllmann, Jochen; Van Damme, Els J M; Peumans, Willy J; Ziesenitz, Maike; Schumacher, Udo

    2002-01-01

    The lectin Chelidonium majus agglutinin (CMA) was previously shown to visualise endothelia of all blood vessels and those lining sinuses of red pulp, stromal reticular meshwok (RM) and dendritic cells of lymphatic follicles in white pulp of the spleen in rats. The aim of the present study was the analysis of CMA and some other lectins in labelling RM, vascular structures and macrophages in lymph nodes of rats. It appeared that CMA stained the entire RM, dendritic cells, lining cells of sinuses and all types of blood vessels. Sinus-lining cells of lymph nodes were labelled with CMA and mannose-, GalNac-, and sialic acid-specific lectins. Moreover, lymph node macrophages were labelled above all by mannose specific lectins. The broad lectin-binding pattern of sinuses--not observed in rat spleen- and CMA-reactivity of both sinus-lining and dendritic cells corroborates the hypothesis that lymph node sinus-lining endothelia are precursors or a special type of immune accessory cells.

  2. Y-chromosome R-M343 African Lineages and Sickle Cell Disease reveal structured assimilation in Lebanon

    PubMed Central

    Haber, Marc; Platt, Daniel E; Khoury, Simon; Badro, Danielle A; Abboud, Miguel; Smith, Chris Tyler; Zalloua, Pierre A

    2012-01-01

    We have sought to identify signals of assimilation of African male lines in Lebanon by exploring the association of sickle cell disease in Lebanon with Y-chromosome haplogroups that are informative of the disease origin and its exclusivity to the Muslim community. A total of 732 samples were analyzed including 33 sickle cell disease patients from Lebanon genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified using populations known to have influenced the genetic structure of the Lebanese population, in addition to African populations with high incidence of sickle cell disease. Y-chromosome haplogroup R-M343 sub-lineages distinguish between sub-Saharan African and Lebanese Y chromosomes. We detected a limited penetration of sickle cell disease into Lebanese R-M343 carriers, restricted to Lebanese Muslims. We suggest that this penetration brought the sickle cell gene along with the African R-M343, probably with the Saharan caravan slave trade. PMID:20981037

  3. Explorative study on the anticancer activity, selectivity and metabolic stability of related analogs of aminosteroid RM-133.

    PubMed

    Perreault, Martin; Maltais, René; Dutour, Raphaël; Poirier, Donald

    2016-11-01

    RM-133 is a key representative of a new family of aminosteroids reported as potent anticancer agents. Although RM-133 produced interesting results in 4 mouse xenograft cancer models when injected subcutaneously, it needs to be improved to increase its in vivo potency. Thus, to obtain an analog of RM-133 with a better drug potential, a structure-activity relationship study was conducted by synthesizing eleven RM-133-related compounds and addressing their antiproliferative activity on 3 human cancer cells (HL-60, OVCAR-3 and PANC-1) and 3 human normal cell lines (primary ovary, pancreas and renal proximal tubule) as well as their metabolic stability in human liver microsomes. When the 2β-tertiary amine of RM-133 was transformed into a salt or moved to position 3β, the anticancer activity was lost. Modifying the orientation of the side chain of RM-133 increased anticancer activity and selectivity, but led to a drastic loss of stability. The protection of the 3α-hydroxyl of RM-133 by the formation of an ester or a carbamate stabilized the molecule against the phase I metabolic enzymes without affecting its anticancer activity. In comparison to RM-133, the 3-dimethylcarbamate derivative 3 is more selective for cancer cells over normal cells and is much more stable in liver microsomes. Those results support the use of a pro-drug strategy targeting the 3α-hydroxyl of RM-133 as an approach to improve its drug properties. The work presented will enable the development of an optimized anticancer drug of the aminosteroid family that is suitable for a future phase I clinical trial. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Argiris, Athanassios; Harrington, Kevin J.; Tahara, Makoto; Schulten, Jeltje; Chomette, Pauline; Ferreira Castro, Ana; Licitra, Lisa

    2017-01-01

    The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the “EXTREME” regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing regimens with ICIs, alone and in combination with other ICIs or CT, with the EXTREME regimen for first-line treatment of R/M SCCHN. As we eagerly await the results of these trials, the EXTREME regimen remains the standard of care for the first-line treatment of R/M SCCHN. PMID:28536670

  5. Parallel Solid-Phase Synthesis Using a New Diethylsilylacetylenic Linker and Leading to Mestranol Derivatives with Potent Antiproliferative Activities on Multiple Cancer Cell Lines.

    PubMed

    Dutour, Raphael; Maltais, Rene; Perreault, Martin; Roy, Jenny; Poirier, Donald

    2018-03-07

    RM-133 belongs to a new family of aminosteroid derivatives demonstrating interesting anticancer properties, as confirmed in vivo in four mouse cancer xenograft models. However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to the development of the mestranol derivative RM-581. Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilyl acetylenic linker. To establish structure-activity relationships, we then investigated their antiproliferative potency on a panel of cancer cell lines from various cancers (breast, prostate, ovarian and pancreatic). Some of the mestranol derivatives have shown in vitro anticancer activities that are close to, or better than those observed for RM-581. Compound 23, a mestranol derivative having a ((3,5-dimethylbenzoyl)-L-prolyl)piperazine side chain at position C2, was found to be active as an antiproliferative agent (IC50 = 0.38 ± 0.34 to 3.17 ± 0.10 µM) and to be twice as active as RM-581 on LNCaP, PC-3, MCF-7, PANC-1 and OVCAR-3 cancer cells (IC50 = 0.56 ± 0.30, 0.89 ± 0.63, 1.36 ± 0.31, 2.47 ± 0.91 and 3.17 ± 0.10 µM, respectively). Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chemistry, this promising candidate could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Targeting the Ron-Dek Signaling Axis in Breast Cancer

    DTIC Science & Technology

    2015-09-01

    myeloid cells exacerbate LPS-induced acute lung injury in the murine lung. Innate immunity. 2011; 17:499–507. 25. Stuart WD, Kulkarni RM, Gray JK...activation in human and murine breast cancer cell lines induces the accumulation of Dek protein. This accumulation of Dek is significant as Dek...overexpression in breast cancer cell lines leads to increases in cell growth and migration while Dek depletion in breast cancer cells leads to dramatic

  7. Nivolumab in squamous cell carcinoma of the head and neck.

    PubMed

    Specenier, Pol

    2018-05-01

    The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.

  8. Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

    PubMed

    Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

    2014-04-01

    The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Sera of patients with recurrent miscarriages containing anti-trophoblast antibodies (ATAB) reduce hCG and progesterone production in trophoblast cells in vitro.

    PubMed

    von Schönfeldt, Viktoria; Rogenhofer, Nina; Ruf, Katharina; Thaler, Christian J; Jeschke, Udo

    2016-09-01

    Reproductive failure including RM has been suggested to correlate with antibodies that cross react with HLA-negative syncytiotrophoblasts and we have reported that 17% of women with 2 or more miscarriages and 34% of women with 3 or more miscarriages express anti-trophoblast antibodies (ATAB). Until now, the mechanism, how ATAB interfere with pregnancy success is not known. HCG and progesterone both play fundamental roles in supporting human pregnancy. Therefore we investigated the effects of sera of RM patients containing ATAB on the hCG and progesterone production of cells of the choriocarcinoma cell line JEG-3. In vitro study to investigate effects of patient sera with and without ATAB on hCG and progesterone secretion of JEG-3 cells. The presence of ATAB was detected as described earlier. Effects of sera from ATAB positive and ATAB negative RM patients on hCG and progesterone secretion by JEG-3 cells were analysed 12 and 24h after plating. Sera of women without pregnancy pathologies served as controls. Sera of ATAB-positive RM patients significantly inhibit hCG secretion of JEG-3 cells for 12h after plating compared to sera of healthy controls (p=0.019) and significantly reduce progesterone production for 12h (p=0.046) and 24h (p=0.027) of co-culture. Sera of ATAB-negative RM patient show no significant effect on progesterone secretion. Inhibition of hCG and progesterone production might point to a mechanism, how ATAB interfere with early pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Thiazolides inhibit growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in human colon cancer cells.

    PubMed

    Müller, Joachim; Sidler, Daniel; Nachbur, Ueli; Wastling, Jonathan; Brunner, Thomas; Hemphill, Andrew

    2008-10-15

    Thiazolides are a novel class of broad-spectrum anti-infective drugs with promising in vitro and in vivo activities against intracellular and extracellular protozoan parasites. The nitrothiazole-analogue nitazoxanide (NTZ; 2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide) represents the thiazolide parent compound, and a number of bromo- and carboxy-derivatives with differing activities have been synthesized. Here we report that NTZ and the bromo-thiazolide RM4819, but not the carboxy-thiazolide RM4825, inhibited proliferation of the colon cancer cell line Caco2 and nontransformed human foreskin fibroblasts (HFF) at or below concentrations the compounds normally exhibit anti-parasitic activity. Thiazolides induced typical signs of apoptosis, such as nuclear condensation, DNA fragmentation and phosphatidylserine exposure. Interestingly, the apoptosis-inducing effect of thiazolides appeared to be cell cycle-dependent and induction of cell cycle arrest substantially inhibited the cell death-inducing activity of these compounds. Using affinity chromatography and mass spectrometry glutathione-S-transferase P1 (GSTP1) from the GST class Pi was identified as a major thiazolide-binding protein. GSTP1 expression was more than 10 times higher in the thiazolide-sensitive Caco2 cells than in the less sensitive HFF cells. The enzymatic activity of recombinant GSTP1 was strongly inhibited by thiazolides. Silencing of GSTP1 using siRNA rendered cells insensitive to RM4819, while overexpression of GSTP1 increased sensitivity to RM4819-induced cell death. Thiazolides may thus represent an interesting novel class of future cancer therapeutics.

  11. CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.

    PubMed

    Gillison, Maura L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Iglesias Docampo, Lara Carmen; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Monga, Manish; Lynch, Mark; Li, Li; Ferris, Robert L

    2018-06-04

    Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018. © AlphaMed Press 2018.

  12. Genome characterization of a breeding line derived from a cross between Oryza sativa and Oryza rufipogon.

    PubMed

    Keong, B P; Harikrishna, J A

    2012-02-01

    A preliminary screening was conducted on BC3F1 and BC4F1 backcross families developed from crossing Oryza sativa (MR219) and O. rufipogon (IRGC105491). Despite earlier results showing that O. rufipogon alleles (wild introgression) contributed to both number of panicles (qPPL-2) and tillers (qTPL-2) at loci RM250, RM208, and RM48 in line A20 of the BC2F2 population, we observed that wild introgression was lost at loci RM250 and RM208 but retained at locus RM48 in BC3F1 and BC4F1. Progeny tests conducted utilizing genotype and phenotype data on both BC4F1 and a reference population, BC2F7 (A20 line), did not show significant differences between groups having the MR219 allele and wild introgression at locus RM48. This suggests that there is no additive and transgressive effect of wild introgression in the BC3F1 and BC4F1 generated. The presence of wild introgression was largely due to gene contamination by cross-pollination during field breeding practices.

  13. Efficient Secretion of Recombinant Proteins from Rice Suspension-Cultured Cells Modulated by the Choice of Signal Peptide.

    PubMed

    Huang, Li-Fen; Tan, Chia-Chun; Yeh, Ju-Fang; Liu, Hsin-Yi; Liu, Yu-Kuo; Ho, Shin-Lon; Lu, Chung-An

    2015-01-01

    Plant-based expression systems have emerged as a competitive platform in the large-scale production of recombinant proteins. By adding a signal peptide, αAmy3sp, the desired recombinant proteins can be secreted outside transgenic rice cells, making them easy to harvest. In this work, to improve the secretion efficiency of recombinant proteins in rice expression systems, various signal peptides including αAmy3sp, CIN1sp, and 33KDsp have been fused to the N-terminus of green fluorescent protein (GFP) and introduced into rice cells to explore the efficiency of secretion of foreign proteins. 33KDsp had better efficiency than αAmy3sp and CIN1sp for the secretion of GFP from calli and suspension-cultured cells. 33KDsp was further applied for the secretion of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) from transgenic rice suspension-cultured cells; approximately 76%-92% of total rice-derived mGM-CSF (rmGM-CSF) was detected in the culture medium. The rmGM-CSF was bioactive and could stimulate the proliferation of a murine myeloblastic leukemia cell line, NSF-60. The extracellular yield of rmGM-CSF reached 31.7 mg/L. Our study indicates that 33KDsp is better at promoting the secretion of recombinant proteins in rice suspension-cultured cell systems than the commonly used αAmy3sp.

  14. STRUCTURE IN THE ROTATION MEASURE SKY

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

    Stil, J. M.; Taylor, A. R.; Sunstrum, C.

    2011-01-01

    An analysis of structure in rotation measure (RM) across the sky based on the RM catalog of Taylor et al. is presented. Several resolved RM structures are identified with structure in the local interstellar medium, including radio loops I, II, and III, the Gum nebula, and the Orion-Eridanus superbubble. Structure functions (SFs) of RM are presented for selected areas, and maps of SF amplitude and slope across the sky are compared with H{alpha} intensity and diffuse polarized intensity. RM variance on an angular scale of 1{sup 0} is correlated with length of the line of sight through the Galaxy, withmore » a contribution from local structures. The slope of the SFs is less concentrated to the Galactic plane and less correlated with length of the line of sight through the Galaxy, suggesting a more local origin for RM structure on angular scales {approx}10{sup 0}. The RM variance is a factor of {approx}2 higher toward the South Galactic Pole than toward the North Galactic Pole, reflecting a more wide-spread asymmetry between the northern and southern Galactic hemispheres. Depolarization of diffuse Galactic synchrotron emission at latitudes <30{sup 0} can be explained largely by Faraday dispersion related to small-scale variance in RM, but the errors allow a significant contribution from differential Faraday rotation along the line of sight.« less

  15. Statistical properties of Faraday rotation measure in external galaxies - I. Intervening disc galaxies

    NASA Astrophysics Data System (ADS)

    Basu, Aritra; Mao, S. A.; Fletcher, Andrew; Kanekar, Nissim; Shukurov, Anvar; Schnitzeler, Dominic; Vacca, Valentina; Junklewitz, Henrik

    2018-06-01

    Deriving the Faraday rotation measure (RM) of quasar absorption line systems, which are tracers of high-redshift galaxies intervening background quasars, is a powerful tool for probing magnetic fields in distant galaxies. Statistically comparing the RM distributions of two quasar samples, with and without absorption line systems, allows one to infer magnetic field properties of the intervening galaxy population. Here, we have derived the analytical form of the probability distribution function (PDF) of RM produced by a single galaxy with an axisymmetric large-scale magnetic field. We then further determine the PDF of RM for one random sight line traversing each galaxy in a population with a large-scale magnetic field prescription. We find that the resulting PDF of RM is dominated by a Lorentzian with a width that is directly related to the mean axisymmetric large-scale field strength of the galaxy population if the dispersion of B0 within the population is smaller than . Provided that RMs produced by the intervening galaxies have been successfully isolated from other RM contributions along the line of sight, our simple model suggests that in galaxies probed by quasar absorption line systems can be measured within ≈50 per cent accuracy without additional constraints on the magneto-ionic medium properties of the galaxies. Finally, we discuss quasar sample selection criteria that are crucial to reliably interpret observations, and argue that within the limitations of the current data base of absorption line systems, high-metallicity damped Lyman-α absorbers are best suited to study galactic dynamo action in distant disc galaxies.

  16. THE SLOAN DIGITAL SKY SURVEY REVERBERATION MAPPING PROJECT: TECHNICAL OVERVIEW

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

    Shen, Yue; Brandt, W. N.; Dawson, Kyle S.

    2015-01-01

    The Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project is a dedicated multi-object RM experiment that has spectroscopically monitored a sample of 849 broad-line quasars in a single 7 deg{sup 2} field with the SDSS-III Baryon Oscillation Spectroscopic Survey spectrograph. The RM quasar sample is flux-limited to i {sub psf} = 21.7 mag, and covers a redshift range of 0.1 < z < 4.5 without any other cuts on quasar properties. Optical spectroscopy was performed during 2014 January-July dark/gray time, with an average cadence of ∼4 days, totaling more than 30 epochs. Supporting photometric monitoring in the g and i bandsmore » was conducted at multiple facilities including the Canada-France-Hawaii Telescope (CFHT) and the Steward Observatory Bok telescope in 2014, with a cadence of ∼2 days and covering all lunar phases. The RM field (R.A., decl. = 14:14:49.00, +53:05:00.0) lies within the CFHT-LS W3 field, and coincides with the Pan-STARRS 1 (PS1) Medium Deep Field MD07, with three prior years of multi-band PS1 light curves. The SDSS-RM six month baseline program aims to detect time lags between the quasar continuum and broad line region (BLR) variability on timescales of up to several months (in the observed frame) for ∼10% of the sample, and to anchor the time baseline for continued monitoring in the future to detect lags on longer timescales and at higher redshift. SDSS-RM is the first major program to systematically explore the potential of RM for broad-line quasars at z > 0.3, and will investigate the prospects of RM with all major broad lines covered in optical spectroscopy. SDSS-RM will provide guidance on future multi-object RM campaigns on larger scales, and is aiming to deliver more than tens of BLR lag detections for a homogeneous sample of quasars. We describe the motivation, design, and implementation of this program, and outline the science impact expected from the resulting data for RM and general quasar science.« less

  17. The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers.

    PubMed

    Kenmogne, Lucie Carolle; Ayan, Diana; Roy, Jenny; Maltais, René; Poirier, Donald

    2015-01-01

    Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies.

  18. The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers

    PubMed Central

    Kenmogne, Lucie Carolle; Ayan, Diana; Roy, Jenny; Maltais, René; Poirier, Donald

    2015-01-01

    Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies. PMID:26660672

  19. Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors

    PubMed Central

    de Souza, Devandir Antonio; Borges, Antonio Carlos; Santana, Ana Carolina; Oliver, Constance; Jamur, Maria Célia

    2015-01-01

    Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization. PMID:26633538

  20. ReadMax—a novel reading and scoring approach for EGFR gene copy number to predict therapeutic benefit of erlotinib treatment in EGFR wild‐type non‐small‐cell lung cancer

    PubMed Central

    Soulières, Denis; Klughammer, Barbara

    2015-01-01

    Abstract EGFR mutation testing is now well established as a means of selecting the optimal first‐line therapy for patients with advanced non‐small‐cell lung cancer (NSCLC). However, deciding on the correct treatment for EGFR wild‐type NSCLC remains a challenge. EGFR fluorescence in‐situ hybridization (FISH) testing of gene copy number has been a promising marker, but has provided mixed results despite attempts to standardize the reading and scoring process. The novel ReadMax reading and scoring system focuses on the most aberrant cells, to identify oncogene addiction, rather than taking a representative reading as in the Colorado method. The methodology was developed using historical samples from the TRUST and MERIT studies, followed by re‐reading of the samples from the SATURN trial. Analysis of samples using the ReadMax methodology revealed that progression‐free survival (PFS) and overall survival (OS) were improved in patients with ReadMax FISH‐positive (RM FISH+) tumours, compared with those whose tumours were not RM FISH+: PFS hazard ratios (HRs) were 0.52 for RM FISH+ versus 0.93 for not RM FISH+; OS HRs were 0.69 and 0.92, respectively. For PFS, HR for RM FISH+ versus not RM FISH+ in the SATURN erlotinib group was 0.53 (p = 0.003). The PFS and OS results were also similar in the EGFR wild‐type population (PFS HRs were 0.63 and 0.96; OS HRs were 0.61 and 0.84, respectively), although amplification of the EGFR gene in patients with EGFR wild‐type disease was not found to be predictive of treatment outcomes, which was unexpected but not unprecedented. KRAS status was not found to affect outcomes. Further experience is required to refine the ReadMax methodology and fully establish its validity and robustness. In conclusion, the ReadMax scoring system to identify patients with EGFR FISH‐positive NSCLC is a promising technique, which could improve treatment options and outcomes for patients with advanced NSCLC, in particular for EGFR wild‐type tumours. PMID:27499899

  1. Revertant mosaicism in heritable skin diseases: mechanisms of natural gene therapy.

    PubMed

    Pasmooij, Anna M G; Jonkman, Marcel F; Uitto, Jouni

    2012-09-01

    Revertant mosaicism (RM) refers to the co-existence of cells carrying disease-causing mutations with cells in which the inherited mutation is genetically corrected by a spontaneous event. It has been discovered in an increasing number of heritable skin diseases: ichthyosis with confetti and different subtypes of epidermolysis bullosa. This "natural gene therapy" phenomenon manifests as normal appearing skin areas surrounded by affected skin. Although initially thought to be rare, RM is now considered relatively common in genetic skin diseases. To address the issues relevant to RM, we here discuss the following questions: 1) What is the incidence of RM in heritable skin diseases? 2) What are the repair mechanisms in RM? 3) When do the revertant mutations occur? 4) How do you recognize revertant skin? 5) Do the areas of RM change in size? The answers to these questions allow us to acquire knowledge on these reverted cells, the mechanisms of RM, and utility of the reverted cells to the advantage of the patient. The revertant skin could potentially be used to treat the patient's own affected skin.

  2. Fine mapping QTL for drought resistance traits in rice (Oryza sativa L.) using bulk segregant analysis.

    PubMed

    Salunkhe, Arvindkumar Shivaji; Poornima, R; Prince, K Silvas Jebakumar; Kanagaraj, P; Sheeba, J Annie; Amudha, K; Suji, K K; Senthil, A; Babu, R Chandra

    2011-09-01

    Drought stress is a major limitation to rice (Oryza sativa L.) yields and its stability, especially in rainfed conditions. Developing rice cultivars with inherent capacity to withstand drought stress would improve rainfed rice production. Mapping quantitative trait loci (QTLs) linked to drought resistance traits will help to develop rice cultivars suitable for water-limited environments through molecular marker-assisted selection (MAS) strategy. However, QTL mapping is usually carried out by genotyping large number of progenies, which is labour-intensive, time-consuming and cost-ineffective. Bulk segregant analysis (BSA) serves as an affordable strategy for mapping large effect QTLs by genotyping only the extreme phenotypes instead of the entire mapping population. We have previously mapped a QTL linked to leaf rolling and leaf drying in recombinant inbred (RI) lines derived from two locally adapted indica rice ecotypes viz., IR20/Nootripathu using BSA. Fine mapping the QTL will facilitate its application in MAS. BSA was done by bulking DNA of 10 drought-resistant and 12 drought-sensitive RI lines. Out of 343 rice microsatellites markers genotyped, RM8085 co-segregated among the RI lines constituting the respective bulks. RM8085 was mapped in the middle of the QTL region on chromosome 1 previously identified in these RI lines thus reducing the QTL interval from 7.9 to 3.8 cM. Further, the study showed that the region, RM212-RM302-RM8085-RM3825 on chromosome 1, harbours large effect QTLs for drought-resistance traits across several genetic backgrounds in rice. Thus, the QTL may be useful for drought resistance improvement in rice through MAS and map-based cloning.

  3. Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection.

    PubMed

    Gimeno, Isabel M; Witter, Richard L; Cortes, Aneg L; Reed, Willie M

    2011-12-01

    The present work is a chronological study of the pathogenesis of three attenuated serotype 1 Marek's disease (MD) virus strains (RM1, CVI988 and 648A80) that provide high protection against MD but have been attenuated by different procedures and induce different degrees of lymphoid organ atrophy. All studied strains replicated in the lymphoid organs (bursa,x thymus and spleen) and a peak of replication was detected at 6 days post inoculation (d.p.i.). Differences, however, were observed among vaccine strains. RM1 strain replicates more in all lymphoid organs compared with CVI988 and 648A80 strains. In addition, replication of RM1 in the thymus did not decrease after 6 d.p.i. but continued at high levels at 14 d.p.i. and until the thymus was completely destroyed. Lung infection occurred very early after infection with all of the three vaccines and the level of replication was similar to that found in the lymphoid organs. Infected cells were very large and appeared scattered in the lung parenchyma and in the parabronchial lining. The study of the target cells for the early infection in cell suspensions of blood and spleen showed that both non-adherent cell populations (enriched in lymphoid cells) and adherent cells (enriched in monocytes/macrophages) supported MD virus infection. Infection in adherent cells was especially high at very early stages of the infection (3 to 6 d.p.i.). Atrophy of lymphoid organs is a major drawback in the production of highly protective vaccines against MD. A better understanding of the mechanisms associated with lymphoid organ atrophy will aid in overcoming this problem.

  4. Genetic evaluation of recombinant inbred lines of rice (Oryza sativa L.) for grain zinc concentrations, yield related traits and identification of associated SSR markers.

    PubMed

    Bekele, Berhanu D; Naveen, G K; Rakhi, S; Shashidhar, H E

    2013-12-01

    The objectives of the present study were to evaluate genetic variability parameters, correlations that exist for grain Zn concentration and yield related traits and identification of SSR markers linked to these traits in rice. One hundred seventy six Recombinant Inbred Lines (RILs) of Azucena X Moromutant were grown at University of Agricultural Sciences, Bangalore in augmented experimental design during wet seasons of 2010 and 2011. The study revealed significant genetic variability for all the traits. Grain yield per plant and grain zinc concentration showed higher phenotypic and genotypic co-efficient of variation. Significant positive correlation was observed for grain yield per plant with number of productive tillers per plant (r = 0.5) and number of tillers per plant (r = 0.4). Grain zinc concentration showed negative correlation with grain yield per plant (r = - 0.27). The path-coefficient analysis indicated the positive direct effect of number of productive tillers per plant on grain yield per plant (0.514). Grain zinc concentration showed negative direct effect on grain yield per plant (-0.186). Single-marker analysis using 26 SSR markers on RILs mapping population showed that RM212, RM263, RM6832, RM152, RM21, RM234 and RM3331 had association with grain zinc concentration and other yield related traits. But validation of these markers on fifty two rice genotypes showed that only three markers RM263, RM152 and RM21 had association with grain zinc concentration. Therefore, the genetic information generated and molecular markers identified from this study could be used for zinc biofortification programmes in rice.

  5. Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

    PubMed

    Tahara, M; Kiyota, N; Yokota, T; Hasegawa, Y; Muro, K; Takahashi, S; Onoe, T; Homma, A; Taguchi, J; Suzuki, M; Minato, K; Yane, K; Ueda, S; Hara, H; Saijo, K; Yamanaka, T

    2018-04-01

    The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. UMIN000010507.

  6. Behavior of restriction–modification systems as selfish mobile elements and their impact on genome evolution

    PubMed Central

    Kobayashi, Ichizo

    2001-01-01

    Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes. PMID:11557807

  7. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

    PubMed

    Kobayashi, I

    2001-09-15

    Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.

  8. Comparison of Predicted and Measured Towline Tensions

    DTIC Science & Technology

    1994-05-01

    10 volts DC Calibration Error Less than 0.25% of full capacity Material Stainless Steel The installed configuration of the load cell at the tow end is...capacity zero shift per IF over operating temperature range. Construction- Stainless steel , seal welded. Electrical Connector- Brantner MSJ-4-BCR...Manufacturer- Marsh & MarineTm Connectors 150 Manufacturer’s Part #- RM-4-MP Description- Molded in-line female connector with stainless steel

  9. Live-Attenuated Lentivirus Immunization Modulates Innate Immunity and Inflammation while Protecting Rhesus Macaques from Vaginal Simian Immunodeficiency Virus Challenge

    PubMed Central

    Genescà, Meritxell; Ma, Zhong-Min; Wang, Yichuan; Assaf, Basel; Qureshi, Huma; Fritts, Linda; Huang, Ying; McChesney, Michael B.

    2012-01-01

    Immunization with attenuated lentiviruses is the only reliable method of protecting rhesus macaques (RM) from vaginal challenge with pathogenic simian immunodeficiency virus (SIV). CD8+ lymphocyte depletion prior to SIVmac239 vaginal challenge demonstrated that a modest, Gag-specific CD8+ T cell response induced by immunization with simian-human immunodeficiency virus 89.6 (SHIV89.6) protects RM. Although CD8+ T cells are required for protection, there is no anamnestic expansion of SIV-specific CD8+ T cells in any tissues except the vagina after challenge. Further, SHIV immunization increased the number of viral target cells in the vagina and cervix, suggesting that the ratio of target cells to antiviral CD8+ T cells was not a determinant of protection. We hypothesized that persistent replication of the attenuated vaccine virus modulates inflammatory responses and limits T cell activation and expansion by inducing immunoregulatory T cell populations. We found that attenuated SHIV infection decreased the number of circulating plasmacytoid dendritic cells, suppressed T cell activation, decreased mRNA levels of proinflammatory mediators, and increased mRNA levels of immunoregulatory molecules. Three days after SIV vaginal challenge, SHIV-immunized RM had significantly more T regulatory cells in the vagina than the unimmunized RM. By day 14 postchallenge, immune activation and inflammation were characteristic of unimmunized RM but were minimal in SHIV-immunized RM. Thus, a modest vaccine-induced CD8+ T cell response in the context of immunoregulatory suppression of T cell activation may protect against vaginal HIV transmission. PMID:22696662

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

    Hirano, Teruyuki; Winn, Joshua N.; Albrecht, Simon

    We present an improved formula for the anomalous radial velocity of the star during planetary transits due to the Rossiter-McLaughlin (RM) effect. The improvement comes from a more realistic description of the stellar absorption line profiles, taking into account stellar rotation, macroturbulence, thermal broadening, pressure broadening, and instrumental broadening. Although the formula is derived for the case in which radial velocities are measured by cross-correlation, we show through numerical simulations that the formula accurately describes the cases where the radial velocities are measured with the iodine absorption-cell technique. The formula relies on prior knowledge of the parameters describing macroturbulence, instrumentalmore » broadening, and other broadening mechanisms, but even 30% errors in those parameters do not significantly change the results in typical circumstances. We show that the new analytic formula agrees with previous ones that had been computed on a case-by-case basis via numerical simulations. Finally, as one application of the new formula, we reassess the impact of the differential rotation on the RM velocity anomaly. We show that differential rotation of a rapidly rotating star may have a significant impact on future RM observations.« less

  11. Whistler turbulence heating of electrons and ions: Three-dimensional particle-in-cell simuations

    DOE PAGES

    Gary, S. Peter; Hughes, R. Scott; Wang, Joseph

    2016-01-14

    In this study, the decay of whistler turbulence in a collisionless, homogeneous, magnetized plasma is studied using three-dimensional particle-in-cell simulations. The simulations are initialized with a narrowband, relatively isotropic distribution of long wavelength whistler modes. A first ensemble of simulations at electron betamore » $${\\beta }_{{\\rm{e}}}$$ = 0.25 and ion-to-electron mass ratio $${m}_{{\\rm{i}}}$$/$${m}_{{\\rm{e}}}$$ = 400 is carried out on a domain cube of dimension $$L{\\omega }_{\\mathrm{pi}}$$/c = 5.12 where $${\\omega }_{\\mathrm{pi}}$$ is the ion plasma frequency. The simulations begin with a range of dimensionless fluctuating field energy densities, $${\\epsilon }_{{\\rm{o}}}$$, and follow the fluctuations as they cascade to broadband, anisotropic turbulence which dissipates at shorter wavelengths, heating both electrons and ions. The electron heating is stronger and preferentially parallel/antiparallel to the background magnetic field $${{\\boldsymbol{B}}}_{{\\rm{o}}};$$ the ion energy gain is weaker and is preferentially in directions perpendicular to $${{\\boldsymbol{B}}}_{{\\rm{o}}}$$. The important new results here are that, over 0.01 < $${\\epsilon }_{{\\rm{o}}}$$ < 0.25, the maximum rate of electron heating scales approximately as $${\\epsilon }_{{\\rm{o}}}$$, and the maximum rate of ion heating scales approximately as $${\\epsilon }_{{\\rm{o}}}^{1.5}$$. A second ensemble of simulations at $${\\epsilon }_{{\\rm{o}}}$$ = 0.10 and $${\\beta }_{{\\rm{e}}}$$ = 0.25 shows that, over 25 < $${m}_{{\\rm{i}}}$$/$${m}_{{\\rm{e}}}\\;$$< 1836, the ratio of the maximum ion heating rate to the maximum electron heating rate scales approximately as $${m}_{{\\rm{e}}}$$/$${m}_{{\\rm{i}}}$$.« less

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

    Li, Yan-Rong; Wang, Jian-Min; Bai, Jin-Ming, E-mail: liyanrong@mail.ihep.ac.cn

    Broad emission lines of active galactic nuclei stem from a spatially extended region (broad-line region, BLR) that is composed of discrete clouds and photoionized by the central ionizing continuum. The temporal behaviors of these emission lines are blurred echoes of continuum variations (i.e., reverberation mapping, RM) and directly reflect the structures and kinematic information of BLRs through the so-called transfer function (also known as the velocity-delay map). Based on the previous works of Rybicki and Press and Zu et al., we develop an extended, non-parametric approach to determine the transfer function for RM data, in which the transfer function ismore » expressed as a sum of a family of relatively displaced Gaussian response functions. Therefore, arbitrary shapes of transfer functions associated with complicated BLR geometry can be seamlessly included, enabling us to relax the presumption of a specified transfer function frequently adopted in previous studies and to let it be determined by observation data. We formulate our approach in a previously well-established framework that incorporates the statistical modeling of continuum variations as a damped random walk process and takes into account long-term secular variations which are irrelevant to RM signals. The application to RM data shows the fidelity of our approach.« less

  13. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.

    PubMed

    Savas, Peter; Virassamy, Balaji; Ye, Chengzhong; Salim, Agus; Mintoff, Christopher P; Caramia, Franco; Salgado, Roberto; Byrne, David J; Teo, Zhi L; Dushyanthen, Sathana; Byrne, Ann; Wein, Lironne; Luen, Stephen J; Poliness, Catherine; Nightingale, Sophie S; Skandarajah, Anita S; Gyorki, David E; Thornton, Chantel M; Beavis, Paul A; Fox, Stephen B; Darcy, Phillip K; Speed, Terence P; Mackay, Laura K; Neeson, Paul J; Loi, Sherene

    2018-06-25

    The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival, particularly in triple-negative and HER2-overexpressing BC subtypes 1 . Although T cells are the predominant TIL population 2 , the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311 T cells isolated from human BCs and show that significant heterogeneity exists in the infiltrating T cell population. We demonstrate that BCs with a high number of TILs contained CD8 + T cells with features of tissue-resident memory T (T RM ) cell differentiation and that these CD8 + T RM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8 + T RM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple-negative breast cancer (TNBC) and provided better prognostication than CD8 expression alone. Our data suggest that CD8 + T RM cells contribute to BC immunosurveillance and are the key targets of modulation by immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of T RM cells will be crucial for successful immunotherapeutic development in BC.

  14. Temperature dependence of line parameters of {}^{12}\\rm{C}{}^{16}\\rm{O}_{2} near 2.004\\,{\\rm{\\mu }}m studied by tunable diode laser spectroscopy

    NASA Astrophysics Data System (ADS)

    Ma, Hongliang; Sun, Mingguo; Zha, Shenlong; Liu, Qiang; Cao, Zhensong; Huang, Yinbo; Zhu, Zhu; Rao, Ruizhong

    2018-02-01

    Not Available Project supported by the Young Scientists Fund of the National Natural Science Foundation of China (Grant Nos. 41205021 and 61701006), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No. 2015264), and the Scientific Research Foundation of the Higher Education Institutions of Anhui Province, China (Grant No. KJ2015A234).

  15. Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double-Blind Placebo-Controlled Study.

    PubMed

    Rafiee, Mitra; Gharagozloo, Marjan; Ghahiri, Ataollah; Mehrabian, Ferdous; Maracy, Mohammad R; Kouhpayeh, Shirin; Pieper, Ina Laura; Rezaei, Abbas

    2015-12-01

    Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL-17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p<0.05). Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.

  16. Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.

    PubMed

    Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Morinaga, Tomonori; Fukuoka, Kazuya; Yamada, Shusai; Murakami, Aki; Kondo, Nobuyuki; Matsumoto, Seiji; Okumura, Yoshitomo; Tanaka, Fumihiro; Hasegawa, Seiki; Hashimoto-Tamaoki, Tomoko; Nakano, Takashi

    2011-12-01

    Array-based comparative genomic hybridization analysis was performed on 21 malignant mesothelioma (MM) samples (16 primary cell cultures and 5 cell lines) and two reactive mesothelial hyperplasia (RM) primary cell cultures. The RM samples did not have any genomic losses or gains. In MM samples, deletions in 1p, 3p21, 4q, 9p21, 16p13 and 22q were detected frequently. We focused on 3p21 because this deletion was specific to the epithelioid type. Especially, a deletion in 3p21.1 region carrying seven genes including SEMA3G was found in 52% of MM samples (11 of 14 epithelioid samples). The allele loss of 3p21.1 might be a good marker for the epithelioid MM. A homozygous deletion in this region was detected in two MM primary cell cultures. A heterozygous deletion detected in nine samples contained the 3p21.1 region and 3p21.31 one carrying the candidate tumor suppressor genes such as semaphorin 3F (SEMA3F), SEMA3B and Ras association (RalGDS/AF-6) domain family member 1 (RASSF1A). SEMA3B, 3F and 3G are class 3 semaphorins and inhibit growth by competing with vascular endothelial growth factor (VEGF) through binding to neuropilin. All MM samples downregulated the expression of more than one gene for SEMA3B, 3F and 3G when compared with Met5a, a normal pleura-derived cell line. Moreover, in 12 of 14 epithelioid MM samples the expression level of SEMA3A was lower than that in Met5a and the two RM samples. An augmented expression of VEGFA was detected in half of the MM samples. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a, RMs and the non-epithelioid MMs. Our data suggest that the downregulated expression of SEMA3A and several SEMA3s results in a loss of inhibitory activities in tumor angiogenesis and tumor growth of VEGFA; therefore, it may play an important role on the pathogenesis of the epithelioid type of MM.

  17. Broadband Photometric Reverberation Mapping Analysis on SDSS-RM and Stripe 82 Quasars

    NASA Astrophysics Data System (ADS)

    Zhang, Haowen; Yang, Qian; Wu, Xue-Bing

    2018-02-01

    We modified the broadband photometric reverberation mapping (PRM) code, JAVELIN, and tested the availability to get broad-line region time delays that are consistent with the spectroscopic reverberation mapping (SRM) project SDSS-RM. The broadband light curves of SDSS-RM quasars produced by convolution with the system transmission curves were used in the test. We found that under similar sampling conditions (evenly and frequently sampled), the key factor determining whether the broadband PRM code can yield lags consistent with the SRM project is the flux ratio of the broad emission line to the reference continuum, which is in line with the previous findings. We further found a critical line-to-continuum flux ratio, about 6%, above which the mean of the ratios between the lags from PRM and SRM becomes closer to unity, and the scatter is pronouncedly reduced. We also tested our code on a subset of SDSS Stripe 82 quasars, and found that our program tends to give biased lag estimations due to the observation gaps when the R-L relation prior in Markov Chain Monte Carlo is discarded. The performance of the damped random walk (DRW) model and the power-law (PL) structure function model on broadband PRM were compared. We found that given both SDSS-RM-like or Stripe 82-like light curves, the DRW model performs better in carrying out broadband PRM than the PL model.

  18. 75 FR 64366 - Advisory Committee on Reactor Safeguards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... NUREG/CR- 6997, ``Modeling a Digital Feedwater Control System Using Traditional Probabilistic Risk.../reading-rm/adams.html or http://www.nrc.gov/reading-rm/doc-collections/ACRS/ . Video teleconferencing... line charges and for providing the equipment and facilities that they use to establish the video...

  19. The Role of the Y-Chromosome in the Establishment of Murine Hybrid Dysgenesis and in the Analysis of the Nucleotide Sequence Organization, Genetic Transmission and Evolution of Repeated Sequences.

    NASA Astrophysics Data System (ADS)

    Nallaseth, Ferez Soli

    The Y-chromosome presents a unique cytogenetic framework for the evolution of nucleotide sequences. Alignment of nine Y-chromosomal fragments in their increasing Y-specific/non Y-specific (male/female) sequence divergence ratios was directly and inversely related to their interspersion on these two respective genomic fractions. Sequence analysis confirmed a direct relationship between divergence ratios and the Alu, LINE-1, Satellite and their derivative oligonucleotide contents. Thus their relocation on the Y-chromosome is followed by sequence divergence rather than the well documented concerted evolution of these non-coding progenitor repeated sequences. Five of the nine Y-chromosomal fragments are non-pseudoautosomal and transcribed into heterogeneous PolyA^+ RNA and thus can be retrotransposed. Evolutionary and computer analysis identified homologous oligonucleotide tracts in several human loci suggesting common and random mechanistic origins. Dysgenic genomes represent the accelerated evolution driving sequence divergence (McClintock, 1984). Sex reversal and sterility characterizing dysgenesis occurs in C57BL/6JY ^{rm Pos} but not in 129/SvY^{rm Pos} derivative strains. High frequency, random, multi-locus deletion products of the feral Y^{ rm Pos}-chromosome are generated in the germlines of F1(C57BL/6J X 129/SvY^{ rm Pos})(male) and C57BL/6JY ^{rm Pos}(male) but not in 129/SvY^{rm Pos}(male). Equal, 10^{-1}, 10^ {-2}, and 0 copies (relative to males) of Y^{rm Pos}-specific deletion products respectively characterize C57BL/6JY ^{rm Pos} (HC), (LC), (T) and (F) females. The testes determining loci of inactive Y^{rm Pos}-chromosomes in C57BL/6JY^{rm Pos} HC females are the preferentially deleted/rearranged Y ^{rm Pos}-sequences. Disruption of regulation of plasma testosterone and hepatic MUP-A mRNA levels, TRD of a 4.7 Kbp EcoR1 fragment suggest disruption of autosomal/X-chromosomal sequences. These data and the highly repeated progenitor (Alu, GATA, LINE-1) sequence content of deletion products confirmed the previously unidentified loss of genetic control of mammalian chromosome biology and hybrid dysgenesis.

  20. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

    PubMed Central

    Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

  1. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice.

    PubMed

    Pradhan, Sharat Kumar; Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai; Pandit, Elssa

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.

  2. Brain-resident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation.

    PubMed

    Brizić, Ilija; Šušak, Božo; Arapović, Maja; Huszthy, Peter C; Hiršl, Lea; Kveštak, Daria; Juranić Lisnić, Vanda; Golemac, Mijo; Pernjak Pugel, Ester; Tomac, Jelena; Oxenius, Annette; Britt, William J; Arapović, Jurica; Krmpotić, Astrid; Jonjić, Stipan

    2018-06-01

    Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8 + T cells in the brain following infection of newborn mice. We show that CD8 + T cells infiltrate the brain and form a pool of tissue-resident memory T cells (T RM cells) that persist for lifetime. Adoptively transferred virus-specific CD8 + T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as T RM cells. Brain CD8 + T RM cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8 + T RM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Formulated Delivery of Enzyme/Prodrug and Cytokine Gene Therapy to Promote Immune Reduction of Treated and Remote Tumors in Mouse Models of Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    Cunha GR, Donjacour AA, Matusik RJ, Rosen JM. Prostate cancer in a transgenic mouse . Proc Natl Acad Sci U S A.1995;92(8):3439- 43 . Kanai F...data not shown). GFP expression in all cell lines was confirmed by UV microscopy and flow cytometry . Evaluation of RM1 cells for assessment of CDUPRT...for prostate cancer in a mouse model that imitates the development of human disease. J. Gene Med. (2004) 6(1): 43 -54. 108. MARTINIELLO-WILKS R

  4. Probing the Plasma Structure of HII Regions with Faraday Rotation

    NASA Astrophysics Data System (ADS)

    Costa, Allison; Spangler, Steven R.

    2018-01-01

    We are involved in study concerning the modification of magnetic fields in the shells of HII regions. We report Faraday Rotation results of lines on sight through or near HII regions associated with OB associations. In the our studies of the Rosette Nebula (l = 206°, b = -1.2°), we measure positive rotation measure (RM) values in excess of +40 to +1200 rad m-2 due to the shell of the nebula and a background RM of +147 rad m-2 due to the general interstellar medium (Savage et al. 2013, ApJ, 765, 42; Costa et al. 2016, ApJ, 821, 92). We are currently completing an analysis of observations probing an addition HII region, IC 1805 (l = 135°, b = +0.9°), associated with the W4 Superbubble. We measure negative RM values across the region between -68 and -961 rad m-2. We find the highest RM values for lines of sight which intersect the ionized shell of the HII region for the Rosette Nebula, but in the case of IC 1805, the highest RM values are outside the bright shell of the HII region. However, we find that the magnitude of the RM between the two regions is similar. The sign of the RM across each HII region is consistent with the expected polarity of a Galactic magnetic field that follows the Perseus spiral arm in the clockwise direction, as suggested by Han et al. (2006, ApJ, 642, 868) and Van Eck et al. (2011, ApJ, 728, 14).

  5. Model-based observer and feedback control design for a rigid Joukowski foil in a Kármán vortex street.

    PubMed

    Free, Brian A; Paley, Derek A

    2018-03-14

    Obstacles and swimming fish in flow create a wake with an alternating left/right vortex pattern known as a Kármán vortex street and reverse Kármán vortex street, respectively. An energy-efficient fish behavior resembling slaloming through the vortex street is called Kármán gaiting. This paper describes the use of a bioinspired array of pressure sensors on a Joukowski foil to estimate and control flow-relative position in a Kármán vortex street using potential flow theory, recursive Bayesian filtering, and trajectory-tracking feedback control. The Joukowski foil is fixed in downstream position in a flowing water channel and free to move on air bearings in the cross-stream direction by controlling its angle of attack to generate lift. Inspired by the lateral-line neuromasts found in fish, the sensing and control scheme is validated using off-the-shelf pressure sensors in an experimental testbed that includes a flapping device to create vortices. We derive a potential flow model that describes the flow over a Joukowski foil in a Kármán vortex street and identify an optimal path through a Kármán vortex street using empirical observability. The optimally observable trajectory is one that passes through each vortex in the street. The estimated vorticity and location of the Kármán vortex street are used in a closed-loop control to track either the optimally observable path or the energetically efficient gait exhibited by fish. Results from the closed-loop control experiments in the flow tank show that the artificial lateral line in conjunction with a potential flow model and Bayesian estimator allow the robot to perform fish-like slaloming behavior in a Kármán vortex street. This work is a precursor to an autonomous robotic fish sensing the wake of another fish and/or performing pursuit and schooling behavior.

  6. A Non-parametric Approach to Constrain the Transfer Function in Reverberation Mapping

    NASA Astrophysics Data System (ADS)

    Li, Yan-Rong; Wang, Jian-Min; Bai, Jin-Ming

    2016-11-01

    Broad emission lines of active galactic nuclei stem from a spatially extended region (broad-line region, BLR) that is composed of discrete clouds and photoionized by the central ionizing continuum. The temporal behaviors of these emission lines are blurred echoes of continuum variations (I.e., reverberation mapping, RM) and directly reflect the structures and kinematic information of BLRs through the so-called transfer function (also known as the velocity-delay map). Based on the previous works of Rybicki and Press and Zu et al., we develop an extended, non-parametric approach to determine the transfer function for RM data, in which the transfer function is expressed as a sum of a family of relatively displaced Gaussian response functions. Therefore, arbitrary shapes of transfer functions associated with complicated BLR geometry can be seamlessly included, enabling us to relax the presumption of a specified transfer function frequently adopted in previous studies and to let it be determined by observation data. We formulate our approach in a previously well-established framework that incorporates the statistical modeling of continuum variations as a damped random walk process and takes into account long-term secular variations which are irrelevant to RM signals. The application to RM data shows the fidelity of our approach.

  7. Reference materials for cellular therapeutics.

    PubMed

    Bravery, Christopher A; French, Anna

    2014-09-01

    The development of cellular therapeutics (CTP) takes place over many years, and, where successful, the developer will anticipate the product to be in clinical use for decades. Successful demonstration of manufacturing and quality consistency is dependent on the use of complex analytical methods; thus, the risk of process and method drift over time is high. The use of reference materials (RM) is an established scientific principle and as such also a regulatory requirement. The various uses of RM in the context of CTP manufacturing and quality are discussed, along with why they are needed for living cell products and the analytical methods applied to them. Relatively few consensus RM exist that are suitable for even common methods used by CTP developers, such as flow cytometry. Others have also identified this need and made proposals; however, great care will be needed to ensure any consensus RM that result are fit for purpose. Such consensus RM probably will need to be applied to specific standardized methods, and the idea that a single RM can have wide applicability is challenged. Written standards, including standardized methods, together with appropriate measurement RM are probably the most appropriate way to define specific starting cell types. The characteristics of a specific CTP will to some degree deviate from those of the starting cells; consequently, a product RM remains the best solution where feasible. Each CTP developer must consider how and what types of RM should be used to ensure the reliability of their own analytical measurements. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  8. Trigger-happy resident memory CD4+ T cells inhabit the human lungs.

    PubMed

    Oja, A E; Piet, B; Helbig, C; Stark, R; van der Zwan, D; Blaauwgeers, H; Remmerswaal, E B M; Amsen, D; Jonkers, R E; Moerland, P D; Nolte, M A; van Lier, R A W; Hombrink, P

    2018-05-01

    Resident memory T cells (T RM ) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8 + T RM have been extensively characterized, the properties of CD4 + T RM remain unclear. Here we determined the transcriptional signature of CD4 + T RM , identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4 + T RM , whereas expression of tissue egress and lymph node homing molecules were low. CD103 + T RM expressed low levels of T-bet, only a small portion expressed Eomesodermin (Eomes), and although the mRNA levels for Hobit were increased, protein expression was absent. On the other hand, the CD103 + T RM showed a Notch signature. CD4 + CD103 + T RM constitutively expressed high transcript levels of numerous cytotoxic mediators that was functionally reflected by a fast recall response, magnitude of cytokine production, and a high degree of polyfunctionality. Interestingly, the superior cytokine production appears to be because of an accessible interferon-γ (IFNγ) locus and was partially because of rapid translation of preformed mRNA. Our studies provide a molecular understanding of the maintenance and potential function of CD4 + T RM in the human lung. Understanding the specific properties of CD4 + T RM is required to rationally improve vaccine design.

  9. REGENERATIVE MEDICINE AS APPLIED TO GENERAL SURGERY

    PubMed Central

    Orlando, Giuseppe; Wood, Kathryn J; De Coppi, Paolo; Baptista, Pedro M; Binder, Kyle W; Bitar, Khalil N; Breuer, Christopher; Burnett, Luke; Christ, George; Farney, Alan; Figliuzzi, Marina; Holmes, James H; Koch, Kenneth; Macchiarini, Paolo; Sani, Sayed-Hadi Mirmalek; Opara, Emmanuel; Remuzzi, Andrea; Rogers, Jeffrey; Saul, Justin M; Seliktar, Dror; Shapira-Schweitzer, Keren; Smith, Tom; Solomon, Daniel; Van Dyke, Mark; Yoo, James J; Zhang, Yuanyuan; Atala, Anthony; Stratta, Robert J; Soker, Shay

    2012-01-01

    The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues or organs in order to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate. PMID:22330032

  10. Downregulation of ILT4+ dendritic cells in recurrent miscarriage and recurrent implantation failure.

    PubMed

    Liu, Su; Wei, Hongxia; Li, Yuye; Huang, Chunyu; Lian, Ruochun; Xu, Jian; Chen, Lanna; Zeng, Yong

    2018-06-14

    The role of ILT4 + DCs in healthy fertile controls and patients with recurrent miscarriages (RM) and recurrent implantation failure (RIF) is unclear. We studied the expression of ILT4 from peripheral blood and endometrial samples from healthy controls and patients with RM and RIF by flow cytometry and immunohistochemistry analysis. Endometrial Foxp3 expression was also investigated using immunohistochemistry. In peripheral blood, there was a significant increase in the percentage of ILT4 + DCs in healthy fertile controls compared with patients with RM and RIF. The presence of ILT4 + DC is even more prominent in the endometrium of healthy fertile controls compared with patients with RM and RIF. Moreover, there was a strong correlation between the number of ILT4 + cells and Foxp3 + Tregs in healthy fertile controls, but not in patients with RM and RIF. Our data indicate that ILT4 + DCs play an important role in the maintenance of immune tolerance during pregnancy, probably through the induction of Foxp3 + Treg cells, a process which is impaired in RM and RIF. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. A Perspective on the Interplay of Ultraviolet-Radiation, Skin Microbiome and Skin Resident Memory TCRαβ+ Cells.

    PubMed

    Patra, VijayKumar; Laoubi, Léo; Nicolas, Jean-François; Vocanson, Marc; Wolf, Peter

    2018-01-01

    The human skin is known to be inhabited by diverse microbes, including bacteria, fungi, viruses, archaea, and mites. This microbiome exerts a protective role against infections by promoting immune development and inhibiting pathogenic microbes to colonize skin. One of the factors having an intense effect on the skin and its resident microbes is ultraviolet-radiation (UV-R). UV-R can promote or inhibit the growth of microbes on the skin and modulate the immune system which can be either favorable or harmful. Among potential UV-R targets, skin resident memory T cells (T RM ) stand as well positioned immune cells at the forefront within the skin. Both CD4 + or CD8 + αβ T RM cells residing permanently in peripheral tissues have been shown to play prominent roles in providing accelerated and long-lived specific immunity, tissue homeostasis, wound repair. Nevertheless, their response upon UV-R exposure or signals from microbiome are poorly understood compared to resident TCRγδ cells. Skin T RM survive for long periods of time and are exposed to innumerable antigens during lifetime. The interplay of T RM with skin residing microbes may be crucial in pathophysiology of various diseases including psoriasis, atopic dermatitis and polymorphic light eruption. In this article, we share our perspective about how UV-R may directly shape the persistence, phenotype, specificity, and function of skin T RM ; and moreover, whether UV-R alters barrier function, leading to microbial-specific skin T RM , disrupting the healthy balance between skin microbiome and skin immune cells, and resulting in chronic inflammation and diseased skin.

  12. Mapping and marker-assisted selection of a brown planthopper resistance gene bph2 in rice (Oryza sativa L.).

    PubMed

    Sun, Li-Hong; Wang, Chun-Ming; Su, Chang-Chao; Liu, Yu-Qiang; Zhai, Hu-Qu; Wan, Jian-Min

    2006-08-01

    Nilaparvata lugens Stål (brown planthopper, BPH), is one of the major insect pests of rice (Oryza sativa L.) in the temperate rice-growing region. In this study, ASD7 harboring a BPH resistance gene bph2 was crossed to a susceptible cultivar C418, a japonica restorer line. BPH resistance was evaluated using 134 F2:3 lines derived from the cross between "ASD7" and "C418". SSR assay and linkage analysis were carried out to detect bph2. As a result, the resistant gene bph2 in ASD7 was successfully mapped between RM7102 and RM463 on the long arm of chromosome 12, with distances of 7.6 cM and 7.2 cM, respectively. Meanwhile, both phenotypic selection and marker-assisted selection (MAS) were conducted in the BC1F1 and BC2F1 populations. Selection efficiencies of RM7102 and RM463 were determined to be 89.9% and 91.2%, respectively. It would be very beneficial for BPH resistance improvement by using MAS of this gene.

  13. The Sloan Digital Sky Survey Reverberation Mapping Project: Composite Lags at z ≤ 1

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

    Li, Jennifer; Shen, Yue; Horne, Keith

    We present composite broad-line region (BLR) reverberation mapping lag measurements for H α , H β , He ii λ 4686, and Mg ii for a sample of 144, z ≲ 1 quasars from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. Using only the 32-epoch spectroscopic light curves in the first six-month season of SDSS-RM observations, we compile correlation function measurements for individual objects and then coadd them to allow the measurement of the average lags for our sample at mean redshifts of 0.4 (for H α ) and ∼0.65 (for the other lines). At similar quasar luminositiesmore » and redshifts, the sample-averaged lag decreases in the order of Mg ii, H α , H β , and He ii. This decrease in lags is accompanied by an increase in the mean line width of the four lines, and is roughly consistent with the virialized motion for BLR gas in photoionization equilibrium. These are among the first RM measurements of stratified BLR structure at z > 0.3. Dividing our sample by luminosity, H α shows clear evidence of increasing lags with luminosity, consistent with the expectation from the measured BLR size–luminosity relation based on H β . The other three lines do not show a clear luminosity trend in their average lags due to the limited dynamic range of luminosity probed and the poor average correlation signals in the divided samples, a situation that will be improved with the incorporation of additional photometric and spectroscopic data from SDSS-RM. We discuss the utility and caveats of composite lag measurements for large statistical quasar samples with reverberation mapping data.« less

  14. The Sloan Digital Sky Survey Reverberation Mapping Project: Composite Lags at z ≤ 1

    NASA Astrophysics Data System (ADS)

    Li, Jennifer; Shen, Yue; Horne, Keith; Brandt, W. N.; Greene, Jenny E.; Grier, C. J.; Ho, Luis C.; Kochanek, Chris; Schneider, Donald P.; Trump, Jonathan R.; Dawson, Kyle S.; Pan, Kaike; Bizyaev, Dmitry; Oravetz, Daniel; Simmons, Audrey; Malanushenko, Elena

    2017-09-01

    We present composite broad-line region (BLR) reverberation mapping lag measurements for Hα, Hβ, He II λ4686, and Mg II for a sample of 144, z ≲ 1 quasars from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. Using only the 32-epoch spectroscopic light curves in the first six-month season of SDSS-RM observations, we compile correlation function measurements for individual objects and then coadd them to allow the measurement of the average lags for our sample at mean redshifts of 0.4 (for Hα) and ˜0.65 (for the other lines). At similar quasar luminosities and redshifts, the sample-averaged lag decreases in the order of Mg II, Hα, Hβ, and He II. This decrease in lags is accompanied by an increase in the mean line width of the four lines, and is roughly consistent with the virialized motion for BLR gas in photoionization equilibrium. These are among the first RM measurements of stratified BLR structure at z > 0.3. Dividing our sample by luminosity, Hα shows clear evidence of increasing lags with luminosity, consistent with the expectation from the measured BLR size-luminosity relation based on Hβ. The other three lines do not show a clear luminosity trend in their average lags due to the limited dynamic range of luminosity probed and the poor average correlation signals in the divided samples, a situation that will be improved with the incorporation of additional photometric and spectroscopic data from SDSS-RM. We discuss the utility and caveats of composite lag measurements for large statistical quasar samples with reverberation mapping data.

  15. INTERPRETATION OF THE STRUCTURE FUNCTION OF ROTATION MEASURE IN THE INTERSTELLAR MEDIUM

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

    Xu, Siyao; Zhang, Bing, E-mail: syxu@pku.edu.cn, E-mail: zhang@physics.unlv.edu

    2016-06-20

    The observed structure function (SF) of rotation measure (RM) varies as a broken power-law function of angular scales. The systematic shallowness of its spectral slope is inconsistent with the standard Kolmogorov scaling. This motivates us to examine the statistical analysis on RM fluctuations. The correlations of RM constructed by Lazarian and Pogosyan are demonstrated to be adequate in explaining the observed features of RM SFs through a direct comparison between the theoretically obtained and observationally measured SF results. By segregating the density and magnetic field fluctuations and adopting arbitrary indices for their respective power spectra, we find that when themore » SFs of RM and emission measure have a similar form over the same range of angular scales, the statistics of the RM fluctuations reflect the properties of density fluctuations. RM SFs can be used to evaluate the mean magnetic field along the line of sight, but cannot serve as an informative source on the properties of turbulent magnetic field in the interstellar medium. We identify the spectral break of RM SFs as the inner scale of a shallow spectrum of electron density fluctuations, which characterizes the typical size of discrete electron density structures in the observed region.« less

  16. Fine mapping of a grain weight quantitative trait locus on rice chromosome 8 using near-isogenic lines derived from a cross between Oryza sativa and Oryza rufipogon.

    PubMed

    Xie, Xiaobo; Song, Mi-Hee; Jin, Fengxue; Ahn, Sang-Nag; Suh, Jung-Pil; Hwang, Hung-Goo; McCouch, S R

    2006-09-01

    A quantitative trait locus (QTL) for grain weight (GW) was detected near SSR marker RM210 on chromosome 8 in backcross populations derived from a cross between the Korean japonica cultivar Hwaseongbyeo and Oryza rufipogon (IRGC 105491). The O. rufipogon allele increased GW in the Hwaseongbyeo background despite the fact that O. rufipogon was the small-seeded parent. Using sister BC(3)F(3) near-isogenic lines (NILs), gw8.1 was validated and mapped to a 6.1 cM region in the interval between RM42 and RM210 (P < or = 0.0001). Substitution mapping with eight BC(3)F(4) sub-NILs further narrowed the interval containing gw8.1 to about 306.4 kb between markers RM23201.CNR151 and RM30000.CNR99. A yield trial using homozygous BC(3)F(4) sister sub-NILs and the Hwaseongbyeo recurrent parent indicated that the NIL carrying an O. rufipogon chromosome segment across the entire gw8.1 target region out-yielded its sister NIL (containing Hwaseongbyeo chromosome in the RM42-RM210 interval) by 9% (P=0.029). The higher-yielding NIL produced 19.3% more grain than the Hwaseongbyeo recurrent parent (P=0.018). Analysis of a BC(3)F(4) NIL indicated that the variation for GW is associated with variation in grain shape, specifically grain length. The locus, gw8.1 is of particular interest because of its independence from undesirable height and grain quality traits. SSR markers tightly linked to the GW QTL will facilitate cloning of the gene underlying this QTL as well as marker-assisted selection for variation in GW in an applied breeding program.

  17. Supermassive Black Holes with High Accretion Rates in Active Galactic Nuclei. VI. Velocity-resolved Reverberation Mapping of the Hβ Line

    NASA Astrophysics Data System (ADS)

    Du, Pu; Lu, Kai-Xing; Hu, Chen; Qiu, Jie; Li, Yan-Rong; Huang, Ying-Ke; Wang, Fang; Bai, Jin-Ming; Bian, Wei-Hao; Yuan, Ye-Fei; Ho, Luis C.; Wang, Jian-Min; SEAMBH Collaboration

    2016-03-01

    In the sixth of a series of papers reporting on a large reverberation mapping (RM) campaign of active galactic nuclei (AGNs) with high accretion rates, we present velocity-resolved time lags of Hβ emission lines for nine objects observed in the campaign during 2012-2013. In order to correct the line broadening caused by seeing and instruments before analyzing the velocity-resolved RM, we adopt the Richardson-Lucy deconvolution to reconstruct their Hβ profiles. The validity and effectiveness of the deconvolution are checked using Monte Carlo simulation. Five among the nine objects show clear dependence of the time delay on velocity. Mrk 335 and Mrk 486 show signatures of gas inflow whereas the clouds in the broad-line regions (BLRs) of Mrk 142 and MCG +06-26-012 tend to be radial outflowing. Mrk 1044 is consistent with having virialized motions. The lags of the remaining four are not velocity-resolvable. The velocity-resolved RM of super-Eddington accreting massive black holes (SEAMBHs) shows that they have diverse kinematics in their BLRs. Comparing with the AGNs with sub-Eddington accretion rates, we do not find significant differences in the BLR kinematics of SEAMBHs.

  18. [Therapeutic effect of rmIL-12 combined with G-CSF on acute radiation sickness produced by γ-ray irradiation in mice].

    PubMed

    Wang, Li; Zhai, Rui-Ren; Pang, Zhao-Xia; Zhang, Chao; Yu, Chang-Lin

    2012-08-01

    The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G-CSF can significantly accelerate the recovery of hematopoietic function in mice with acute radiation sickness.

  19. "We as Human Beings Get Farther and Farther Apart": the experiences of patients with remote monitoring systems.

    PubMed

    Ottenberg, Abigale L; Swetz, Keith M; Mueller, Luke A; Gerhardson, Samantha; Mueller, Paul S

    2013-01-01

    To explore the experiences of patients living with an implantable cardioverter-defibrillator (ICD) who had received remote monitoring (RM). Anecdotal evidence suggests that not all patients with RM use the technology. Focus groups of patients with an ICD who received an RM system. Transcripts reviewed using thematic analysis. Nine patients (3 women and 6 men; median [range] age, 73 [58-91] years) received an RM system. Patients were assigned to a group in regard to RM system use (nonusers, n = 5; users, n = 4). Few nonusers recalled having prior conversations about the system. Users described it as "simple" and "easy" to use. Nonusers often were unsure whether their system was correctly transmitting information. System benefits perceived by users included convenience and security. Nonusers expressed mistrust. Recommendations included early education and help lines. Patient adherence to RM systems can be improved by explaining perceived benefits and addressing barriers to use. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Single-epoch black hole mass estimators for broad-line active galactic nuclei: recalibrating Hβ with a new approach

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

    Feng, Hua; Li, Hong; Shen, Yue

    2014-10-10

    Based on an updated Hβ reverberation mapping (RM) sample of 44 nearby active galactic nuclei (AGNs), we propose a novel approach for black hole (BH) mass estimation using two filtered luminosities computed from single-epoch (SE) AGN spectra around the Hβ region. We found that the two optimal-filter luminosities extract virial information (size and virial velocity of the broad-line region, BLR) from the spectra, justifying their usage in this empirical BH mass estimator. The major advantages of this new recipe over traditional SE BH mass estimators utilizing continuum luminosity and broad-line width are (1) it has a smaller intrinsic scatter ofmore » 0.28 dex calibrated against RM masses, (2) it is extremely simple to use in practice, without any need to decompose the spectrum, and (3) it produces unambiguous and highly repeatable results even with low signal-to-noise spectra. The combination of the two luminosities can also cancel out, to some extent, systematic luminosity errors potentially introduced by uncertainties in distance or flux calibration. In addition, we recalibrated the traditional SE mass estimators using broad Hβ FWHM and monochromatic continuum luminosity at 5100 Å (L {sub 5100}). We found that using the best-fit slopes on FWHM and L {sub 5100} (derived from fitting the BLR radius-luminosity relation and the correlation between rms line dispersion and SE FWHM, respectively) rather than simple assumptions (e.g., 0.5 for L {sub 5100} and 2 for FWHM) leads to more precise SE mass estimates, improving the intrinsic scatter from 0.41 dex to 0.36 dex with respect to the RM masses. We compared different estimators and discussed their applications to the Sloan Digital Sky Survey quasar sample. Due to the limitations of the current RM sample, application of any SE recipe calibrated against RM masses to distant quasars should be treated with caution.« less

  1. Maximal power training induced different improvement in throwing velocity and muscle strength according to playing positions in elite male handball players

    PubMed Central

    Chtourou, H; Souissi, N; Aouidet, A; Chamari, K

    2016-01-01

    This study was designed to assess the effect of strength and power training on throwing velocity and muscle strength in handball players according to their playing positions. Twenty-two male handball players were assigned to either an experimental group (n=11) or a control group (n=11) (age: 22.1 ± 3.0 years). They were asked to complete (i) the ball throwing velocity test and (ii) the one-repetition maximum (1-RM) tests for the half-back squat, the pull-over, the bench press, the developed neck, and the print exercises before and after 12 weeks of maximal power training. The training was designed to improve strength and power with an intensity of 85-95% of the 1RM. In addition to their usual routine handball training sessions, participants performed two sessions per week. During each session, they performed 3-5 sets of 3-8 repetitions with 3 min of rest in between. Then, they performed specific shots (i.e., 12 to 40). Ball-throwing velocity (p<0.001) was higher after the training period in rear line players (RL). The training programme resulted in an improvement of 1RM bench press (p<0.001), 1RM developed neck (p<0.001) and 1RM print (p<0.001) in both front line (FL) and RL. The control group showed a significant improvement only in ball-throwing velocity (p<0.01) and 1RM bench press (p<0.01) in RL. A significantly greater improvement was found in ball-throwing velocity (p<0.001), 1RM bench press (p<0.001), and 1RM half-back squat exercises in players of the central axis (CA) compared to the lateral axis (LA) (p<0.01). The power training programme induced significantly greater increases in ball-throwing velocity and muscle strength in FL than RL and in CA than LA axis players. PMID:28090144

  2. Maximal power training induced different improvement in throwing velocity and muscle strength according to playing positions in elite male handball players.

    PubMed

    Cherif, M; Chtourou, H; Souissi, N; Aouidet, A; Chamari, K

    2016-12-01

    This study was designed to assess the effect of strength and power training on throwing velocity and muscle strength in handball players according to their playing positions. Twenty-two male handball players were assigned to either an experimental group (n=11) or a control group (n=11) (age: 22.1 ± 3.0 years). They were asked to complete (i) the ball throwing velocity test and (ii) the one-repetition maximum (1-RM) tests for the half-back squat, the pull-over, the bench press, the developed neck, and the print exercises before and after 12 weeks of maximal power training. The training was designed to improve strength and power with an intensity of 85-95% of the 1RM. In addition to their usual routine handball training sessions, participants performed two sessions per week. During each session, they performed 3-5 sets of 3-8 repetitions with 3 min of rest in between. Then, they performed specific shots (i.e., 12 to 40). Ball-throwing velocity (p<0.001) was higher after the training period in rear line players (RL). The training programme resulted in an improvement of 1RM bench press (p<0.001), 1RM developed neck (p<0.001) and 1RM print (p<0.001) in both front line (FL) and RL. The control group showed a significant improvement only in ball-throwing velocity (p<0.01) and 1RM bench press (p<0.01) in RL. A significantly greater improvement was found in ball-throwing velocity (p<0.001), 1RM bench press (p<0.001), and 1RM half-back squat exercises in players of the central axis (CA) compared to the lateral axis (LA) (p<0.01). The power training programme induced significantly greater increases in ball-throwing velocity and muscle strength in FL than RL and in CA than LA axis players.

  3. Fine Mapping of QUICK ROOTING 1 and 2, Quantitative Trait Loci Increasing Root Length in Rice.

    PubMed

    Kitomi, Yuka; Nakao, Emari; Kawai, Sawako; Kanno, Noriko; Ando, Tsuyu; Fukuoka, Shuichi; Irie, Kenji; Uga, Yusaku

    2018-02-02

    The volume that the root system can occupy is associated with the efficiency of water and nutrient uptake from soil. Genetic improvement of root length, which is a limiting factor for root distribution, is necessary for increasing crop production. In this report, we describe identification of two quantitative trait loci (QTLs) for maximal root length, QUICK ROOTING 1 ( QRO1 ) on chromosome 2 and QRO2 on chromosome 6, in cultivated rice ( Oryza sativa L.). We measured the maximal root length in 26 lines carrying chromosome segments from the long-rooted upland rice cultivar Kinandang Patong in the genetic background of the short-rooted lowland cultivar IR64. Five lines had longer roots than IR64. By rough mapping of the target regions in BC 4 F 2 populations, we detected putative QTLs for maximal root length on chromosomes 2, 6, and 8. To fine-map these QTLs, we used BC 4 F 3 recombinant homozygous lines. QRO1 was mapped between markers RM5651 and RM6107, which delimit a 1.7-Mb interval on chromosome 2, and QRO2 was mapped between markers RM20495 and RM3430-1, which delimit an 884-kb interval on chromosome 6. Both QTLs may be promising gene resources for improving root system architecture in rice. Copyright © 2018 Kitomi et al.

  4. Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.

    PubMed

    Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Piatak, Michael; Lifson, Jeffrey; Veazey, Ronald S

    2013-11-01

    Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (<30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to <30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to <30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

  5. SUPERMASSIVE BLACK HOLES WITH HIGH ACCRETION RATES IN ACTIVE GALACTIC NUCLEI. VI. VELOCITY-RESOLVED REVERBERATION MAPPING OF THE Hβ LINE

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

    Du, Pu; Lu, Kai-Xing; Hu, Chen

    In the sixth of a series of papers reporting on a large reverberation mapping (RM) campaign of active galactic nuclei (AGNs) with high accretion rates, we present velocity-resolved time lags of Hβ emission lines for nine objects observed in the campaign during 2012–2013. In order to correct the line broadening caused by seeing and instruments before analyzing the velocity-resolved RM, we adopt the Richardson–Lucy deconvolution to reconstruct their Hβ profiles. The validity and effectiveness of the deconvolution are checked using Monte Carlo simulation. Five among the nine objects show clear dependence of the time delay on velocity. Mrk 335 andmore » Mrk 486 show signatures of gas inflow whereas the clouds in the broad-line regions (BLRs) of Mrk 142 and MCG +06-26-012 tend to be radial outflowing. Mrk 1044 is consistent with having virialized motions. The lags of the remaining four are not velocity-resolvable. The velocity-resolved RM of super-Eddington accreting massive black holes (SEAMBHs) shows that they have diverse kinematics in their BLRs. Comparing with the AGNs with sub-Eddington accretion rates, we do not find significant differences in the BLR kinematics of SEAMBHs.« less

  6. Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells.

    PubMed

    Maguire, Greg; Friedman, Peter

    2015-05-26

    The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell's power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely "systems therapeutic", can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics". A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S(2)RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S(2)RM technology, to develop a new class of therapeutics called "systems therapeutics." Given the ubiquitous and powerful nature of innate S(2)RM-based healing in the human body, this "systems therapeutic" approach using S(2)RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications.

  7. Characterization and evaluation of DOTA-conjugated Bombesin/RGD-antagonists for prostate cancer tumor imaging and therapy.

    PubMed

    Stott Reynolds, Tamila J; Schehr, Rebecca; Liu, Dijie; Xu, Jingli; Miao, Yubin; Hoffman, Timothy J; Rold, Tammy L; Lewis, Michael R; Smith, Charles J

    2015-02-01

    Here we present the metallation, characterization, in vivo and in vitro evaluations of dual-targeting, peptide-based radiopharmaceuticals with utility for imaging and potentially treating prostate tumors by virtue of their ability to target the αVβ3 integrin or the gastrin releasing peptide receptor (GRPr). [RGD-Glu-6Ahx-RM2] (RGD: Arg-Gly-Asp; Glu: glutamic acid; 6-Ahx: 6-amino hexanoic acid; RM2: (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2)) was conjugated to a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) bifunctional chelator (BFCA) purified via reversed-phase high-performance liquid chromatography (RP-HPLC), characterized by electrospray ionization-mass spectrometry (ESI-MS), and radiolabeled with (111)In or (177)Lu. Natural-metallated compounds were assessed for binding affinity for the αVβ3 integrin or GRPr in human glioblastoma U87-MG and prostate PC-3 cell lines and stability prior to in vivo evaluation in normal CF-1 mice and SCID mice xenografted with PC-3 cells. Competitive displacement binding assays with PC-3 and U87-MG cells revealed high to moderate binding affinity for the GRPr or the αVβ3 integrin (IC50 range of 5.39±1.37 nM to 9.26±0.00 nM in PC-3 cells, and a range of 255±47 nM to 321±85 nM in U87-MG cells). Biodistribution studies indicated high tumor uptake in PC-3 tumor-bearing mice (average of 7.40±0.53% ID/g at 1h post-intravenous injection) and prolonged retention of tracer (mean of 4.41±0.91% ID/g at 24h post-intravenous injection). Blocking assays corroborated the specificity of radioconjugates for each target. Micro-single photon emission computed tomography (microSPECT) confirmed favorable radiouptake profiles in xenografted mice at 20h post-injection. [RGD-Glu-[(111)In-DO3A]-6-Ahx-RM2] and [RGD-Glu-[(177)Lu- DO3A]-6-Ahx-RM2] show favorable pharmacokinetic and radiouptake profiles, meriting continued evaluation for molecular imaging in murine U87-MG/PC-3 xenograft models and radiotherapy studies with (177)Lu and (90)Y conjugates. These heterovalent, peptide-targeting ligands perform comparably with many mono- and multivalent conjugates with the potential benefit of increased sensitivity for detecting cancer cells exhibiting differential expression of target receptors. Published by Elsevier Inc.

  8. The Sloan Digital Sky Survey Reverberation Mapping Project: Ensemble Spectroscopic Variability of Quasar Broad Emission Lines

    NASA Astrophysics Data System (ADS)

    Sun, Mouyuan; Trump, Jonathan R.; Shen, Yue; Brandt, W. N.; Dawson, Kyle; Denney, Kelly D.; Hall, Patrick B.; Ho, Luis C.; Horne, Keith; Jiang, Linhua; Richards, Gordon T.; Schneider, Donald P.; Bizyaev, Dmitry; Kinemuchi, Karen; Oravetz, Daniel; Pan, Kaike; Simmons, Audrey

    2015-09-01

    We explore the variability of quasars in the Mg ii and {{H}}β broad emission lines and ultraviolet/optical continuum emission using the Sloan Digital Sky Survey Reverberation Mapping project (SDSS-RM). This is the largest spectroscopic study of quasar variability to date: our study includes 29 spectroscopic epochs from SDSS-RM over 6 months, containing 357 quasars with Mg ii and 41 quasars with {{H}}β . On longer timescales, the study is also supplemented with two-epoch data from SDSS-I/II. The SDSS-I/II data include an additional 2854 quasars with Mg ii and 572 quasars with {{H}}β . The Mg ii emission line is significantly variable ({{Δ }}f/f∼ 10% on ∼100-day timescales), a necessary prerequisite for its use for reverberation mapping studies. The data also confirm that continuum variability increases with timescale and decreases with luminosity, and the continuum light curves are consistent with a damped random-walk model on rest-frame timescales of ≳ 5 days. We compare the emission-line and continuum variability to investigate the structure of the broad-line region. Broad-line variability shows a shallower increase with timescale compared to the continuum emission, demonstrating that the broad-line transfer function is not a δ-function. {{H}}β is more variable than Mg ii (roughly by a factor of ∼1.5), suggesting different excitation mechanisms, optical depths and/or geometrical configuration for each emission line. The ensemble spectroscopic variability measurements enabled by the SDSS-RM project have important consequences for future studies of reverberation mapping and black hole mass estimation of 1\\lt z\\lt 2 quasars.

  9. Socio-economic determinants of nutritional status of children in rural peninsular Malaysia.

    PubMed

    Marjan, Z M; Taib, M N; Lin, K G; Siong, T E

    1998-12-01

    The data presented is part of the findings from a four-year collaborative research project between Universiti Putra Malaysia, the Institute for Medical Research and the Ministry of Health Malaysia. The project assessed the nutritional status of the major functional groups in Peninsular Malaysia. Mukim Sayong and Pulau Kemiri in the District of Kuala Kangsar, Perak were two of the subdistricts selected to represent small rubber holdings in Peninsular Malaysia. This paper attempts to analyse the socio-economic profile of the households and the nutritional status of children below 9 years of age. A total of 307 households were studied. Approximately 63% of the households were involved in rubber activities and the majority of them were hired tappers. The average monthly income of the households was RM467 and the income ranged between RM30 to RM2120. Based on the per capita poverty line income of RM84.38, it was found that 14.1% of the households earned less than RM42.19, which can be considered as hard-core poor, while 32.7% were poor (monthly per capita income between RM42.19 and RM84.38). Slightly more than half (52.7%) earned income above the poverty line. The average family size was 4.5, ranging from 1 through to 16. The majority of the heads of households (56.6%) had between 3 and 6 years of education, and 14.5% did not receive any formal education. The prevalence of stunting among children 0-5 years of age was 26%, while 31.5% were underweight and 3.8% wasted. Among children aged between 5 and 9 years, almost the same pattern of nutritional status was noted. The overall percentages of stunting, underweight and wasting among these children were 29.2%, 26.1% and 0.62%, respectively. Analysis on nutritional status according to income level showed a noticeable difference in the prevalence of malnutrition in children above and below the poverty line income. The Student's t-test indicated significant differences in weight-for-age and weight-for-height between the two poverty line income for children below 5 years of age. Pearson's correlation coefficient showed a significant correlation between height-for-age with household size (r = -0.26, p<0.05), and monthly per capita income with weight-for-height (r = 0.25, p<0.05). There was a highly significant correlation between acreage of land cultivated and weight-for-height (r = 0.42, p<0.01), and weight-for-age (r = 0.25, p<0.05). The findings indicated the influence of socio-economic factors on the nutritional status of children.

  10. Regenerative medicine for the respiratory system: distant future or tomorrow's treatment?

    PubMed

    Brouwer, Katrien M; Hoogenkamp, Henk R; Daamen, Willeke F; van Kuppevelt, Toin H

    2013-03-01

    Regenerative medicine (RM) is a new field of biomedical science that focuses on the regeneration of tissues and organs and the restoration of organ function. Although regeneration of organ systems such as bone, cartilage, and heart has attracted intense scientific research over recent decades, RM research regarding the respiratory system, including the trachea, the lung proper, and the diaphragm, has lagged behind. However, the last 5 years have witnessed novel approaches and initial clinical applications of tissue-engineered constructs to restore organ structure and function. In this regard, this article briefly addresses the basics of RM and introduces the key elements necessary for tissue regeneration, including (stem) cells, biomaterials, and extracellular matrices. In addition, the current status of the (clinical) application of RM to the respiratory system is discussed, and bottlenecks and recent approaches are identified. For the trachea, several initial clinical studies have been reported and have used various combinations of cells and scaffolds. Although promising, the methods used in these studies require optimization and standardization. For the lung proper, only (stem) cell-based approaches have been probed clinically, but it is becoming apparent that combinations of cells and scaffolds are required to successfully restore the lung's architecture and function. In the case of the diaphragm, clinical applications have focused on the use of decellularized scaffolds, but novel scaffolds, with or without cells, are clearly needed for true regeneration of diaphragmatic tissue. We conclude that respiratory treatment with RM will not be realized tomorrow, but its future looks promising.

  11. Evidence for Helical Magnetic fields in Kiloparsec-Scale AGN Jets and the Action of a Cosmic Battery

    NASA Technical Reports Server (NTRS)

    Gabuzda, D. C.; Christodoulou, D. M.; Contopulos, I.; Kazanas, D.

    2012-01-01

    A search for transverse kiloparsec-scale gradients in Faraday rotation-measure (RM) maps of extragalactic radio sources in the literature has yielded 6 AGNs displaying continuous, monotonic RM gradients across their jets, oriented roughly orthogonal to the local jet direction. The most natural interpretation of such transverse RM gradients is that they are caused by the systematic change in the line-of-sight components of helical magnetic fields associated with these jets. All the identified transverse RM gradients increase in the counterclockwise (CCW) direction on the sky relative to the centers of these AGNs. Taken together with the results of Contopoulos et al. who found evidence for a predominance of clockwise (CW) transverse RM gradients across parsec-scale (VLBI) jets, this provides new evidence for preferred orientations of RM gradients due to helical jet magnetic fields, with a reversal from CW in the inner jets to CCW farther from the centers of activity. This can be explained by the "Poynting-Robertson cosmic-battery" mechanism, which can generate helical magnetic fields with a. characteristic "twist," which are expelled with the jet outflows. If the Poynting-Robertson battery mechanism is not operating, an alternative mechanism must be identified, which is able to explain the 'predominance of CW /CCW RM gradients on parsec/kiloparsec scales.

  12. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    PubMed

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  13. Probing AGN Structure on Microarcsecond Scales: The Space Telescope and Optical Reverberation Mapping Program

    NASA Astrophysics Data System (ADS)

    De Rosa, Gisella

    2015-08-01

    The unknown dynamics of the broad line region (BLR) gas represents a serious gap in our understanding of active galactic nuclei (AGNs) and, consequently, of the black-hole/host-galaxy co-evolution. By using time resolution as a substitute for spatial resolution, reverberation mapping (RM) is the only technique that allows us to infer both the geometry and the kinematics of the BLR gas, shading light on the BLR role on accretion/feedback processes. In 2014, the AGN STORM team used HST/COS for a RM program for which we obtained 170 UV spectra of the Seyfert 1 galaxy NGC 5548 at a near daily cadence. These data and contemporaneous observations with Swift and ground-based telescopes make this the most intensive RM program ever undertaken. I will report first results of this unique RM experiment.

  14. Mechanical cues in orofacial tissue engineering and regenerative medicine.

    PubMed

    Brouwer, Katrien M; Lundvig, Ditte M S; Middelkoop, Esther; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues. © 2015 by the Wound Healing Society.

  15. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges

    PubMed Central

    Lakhashe, Samir K.; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B.; DiPasquale, Janet M.; Hemashettar, Girish; Yoon, John K.; Rasmussen, Robert A.; Yang, Feng; Lee, Sandra J.; Montefiori, David C.; Novembre, Francis J.; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R.; Robert-Guroff, Marjorie; Johnson, Welkin E.; Lieberman, Judy; Ruprecht, Ruth M.

    2011-01-01

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus >90%; these RM also had strong SIV Gag-specific proliferation of CD8+ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4+ T cells; the latter have been implicated as preferential virus targets in-vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. PMID:21693155

  16. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

    PubMed

    Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

    2011-08-05

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. PhreeqcRM: A reaction module for transport simulators based on the geochemical model PHREEQC

    USGS Publications Warehouse

    Parkhurst, David L.; Wissmeier, Laurin

    2015-01-01

    PhreeqcRM is a geochemical reaction module designed specifically to perform equilibrium and kinetic reaction calculations for reactive transport simulators that use an operator-splitting approach. The basic function of the reaction module is to take component concentrations from the model cells of the transport simulator, run geochemical reactions, and return updated component concentrations to the transport simulator. If multicomponent diffusion is modeled (e.g., Nernst–Planck equation), then aqueous species concentrations can be used instead of component concentrations. The reaction capabilities are a complete implementation of the reaction capabilities of PHREEQC. In each cell, the reaction module maintains the composition of all of the reactants, which may include minerals, exchangers, surface complexers, gas phases, solid solutions, and user-defined kinetic reactants.PhreeqcRM assigns initial and boundary conditions for model cells based on standard PHREEQC input definitions (files or strings) of chemical compositions of solutions and reactants. Additional PhreeqcRM capabilities include methods to eliminate reaction calculations for inactive parts of a model domain, transfer concentrations and other model properties, and retrieve selected results. The module demonstrates good scalability for parallel processing by using multiprocessing with MPI (message passing interface) on distributed memory systems, and limited scalability using multithreading with OpenMP on shared memory systems. PhreeqcRM is written in C++, but interfaces allow methods to be called from C or Fortran. By using the PhreeqcRM reaction module, an existing multicomponent transport simulator can be extended to simulate a wide range of geochemical reactions. Results of the implementation of PhreeqcRM as the reaction engine for transport simulators PHAST and FEFLOW are shown by using an analytical solution and the reactive transport benchmark of MoMaS.

  18. Broadband Photometric Reverberation Mapping Analysis on SDSS-RM and Stripe 82 Quasars

    NASA Astrophysics Data System (ADS)

    Zhang, Haowen; Yang, Qian; Wu, Xuebing; Shen, Yue

    2018-01-01

    We extended the broadband photometric reverberation mapping (PRM) code, JAVELIN and test the availability to get broad line region (BLR) time delays that are consistent with spectroscopic reverberation mapping (SRM) projects. Broadband light curves of SDSS-RM quasars produced by convolution with system transmission curve were used in the test. We find that under similar sampling conditions (evenly and frequently sampled), the key factor determining whether the broadband PRM code can yield lags consistent with spectroscopic projects is the flux ratio of line to the reference continuum, which is in line with the findings in Zu et al. (2016). We further find a crucial line-to-continuum flux ratio, above which the mean of the ratios between the lags from PRM and SRM becomes closer to unity, and the scatter is pronouncedly reduced. Based on this flux ratio criteria, we selected some of the quasars from Hernitschek et al. (2015) and carry out broadband PRM on this subset. The performance of damped random walking (DRW) model and power-law (PL) structure function model on broadband PRM are compared using mock light curves with high, even cadences and low, uneven ones, respectively. We find that DRW model performs better in carrying out broadband PRM than PL model both for high and low cadence light curves with other data qualities similar to SDSS-RM quasars.

  19. Influence of Drought on Mesophyll Resistance to CO2 Diffusion and its Impact on Water-Use Efficiency in Trees

    NASA Astrophysics Data System (ADS)

    Guo, J.; Beverly, D.; Cook, C.; Ewers, B. E.; Williams, D. G.

    2015-12-01

    The resistance to CO2 diffusion inside leaves (mesophyll resistance; rm) during photosynthesis is often comparable in magnitude to stomatal diffusion resistance, and varies among species and across environmental conditions. Consequently, photosynthesis is strongly limited by rm at low internal CO2 partial pressures, such that its variation may determine patterns of leaf water-use efficiency (WUE). Reduction in stomatal conductance with drought typically increases WUE, but also decreases photosynthesis. In theory, the decrease in photosynthesis could be countered by reduction in rm while maintaining high WUE. It is still uncertain how drought-related changes in rm affect short- and long-term WUE strategies of different tree species. We conducted field observations of instantaneous WUE and 13C discrimination in two dominant conifer species (Pinus contorta and Picea engelmannii) in SE Wyoming over the seasonal dry-down period in the summer of 2015. rm was examined by on-line 13C discrimination using isotope laser spectroscopy. Controlled environment studies on three conifer species (P. contorta, P. engelmannii, and Abies lasiocarpa) and one angiosperm (Populus tremuloides) are in progress. We hypothesize that the plasticity of rm in response to drought accounts for significant adjustments in photosynthetic capacity and WUE. Needle leaf conifers are known to have relatively high rm, and we expect them to show greater improvements in photosynthesis and WUE when rm is decreased compared to angiosperm tree species.

  20. Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

    PubMed

    Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

    2018-06-01

    Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  1. A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.

    PubMed

    Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G

    2014-06-01

    Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

  2. Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

    PubMed Central

    Kenmogne, Lucie Carolle; Roy, Jenny; Maltais, René; Rouleau, Mélanie; Neveu, Bertrand; Pouliot, Frédéric; Poirier, Donald

    2017-01-01

    In the fight against androgen-sensitive prostate cancer, the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is an attractive therapeutic target considering its key role in the formation of androgenic steroids. In this study, we attempted to assess the in vivo efficacy of the compound RM-532-105, an androsterone derivative developed as an inhibitor of 17β-HSD3, in the prostate cancer model of androgen-sensitive LAPC-4 cells xenografted in nude mice. RM-532-105 did not inhibit the tumor growth induced by 4-androstene-3,17-dione (4-dione); rather, the levels of the androgens testosterone (T) and dihydrotestosterone (DHT) increased within the tumors. In plasma, however, DHT levels increased but T levels did not. In troubleshooting experiments, the non-androgenic potential of RM-532-105 was confirmed by two different assays (LAPC-4 proliferation and androgen receptor transcriptional activity assays). The enzyme 5α-reductase was also revealed to be the predominant enzyme metabolizing 4-dione in LAPC-4 cells, yielding 5α-androstane-3,17-dione and not T. Other 17β-HSDs than 17β-HSD3 seem responsible in the androgen synthesis. From experiments with LAPC-4 cells, we fortuitously came across the interesting finding that 17β-HSD3 inhibitor RM-532-105 is concentrated inside tumors. PMID:28182747

  3. Regenerative medicine in Brazil: small but innovative.

    PubMed

    McMahon, Dominique S; Singer, Peter A; Daar, Abdallah S; Thorsteinsdóttir, Halla

    2010-11-01

    Although Brazil has received attention for conducting one of the world's largest stem cell clinical trials for heart disease, little has been published regarding Brazil's regenerative medicine (RM) sector. Here we present a comprehensive case study of RM in Brazil, including analysis of the current activity, the main motivations for engaging in RM and the remaining challenges to development in this field. Our case study is primarily based on semi-structured interviews with experts on RM in Brazil, including researchers, policymakers, clinicians, representatives of firms and regulators. Driven by domestic health needs and strategic government support, Brazil is producing innovative RM research, particularly for clinical research in cardiology, orthopedics, diabetes and neurology. We describe the main RM research currently taking place in Brazil, as well as some of the economic, regulatory and policy events that have created a favorable environment for RM development. Brazilian RM researchers need to overcome several formidable challenges to research: research funding is inconsistent, importation of materials is costly and slow, and weak linkages between universities, hospitals and industry impede translational research. Although Brazil's contribution to the RM sector is small, its niche emphasis on clinical applications may become of global importance, particularly if Brazil manages to address the challenges currently impinging on RM innovation.

  4. Fundamentals of protein and cell interactions in biomaterials.

    PubMed

    Aiyelabegan, Hammed Tanimowo; Sadroddiny, Esmaeil

    2017-04-01

    The extracellular matrix (ECM) is an active and complex microenvironment with outstanding biomechanical, biophysical, and biochemical characteristics, which can indirectly or directly controls cell adhesion, migration, proliferation, and differentiation, as well as partaking in regeneration and homeostasis of organs and tissues. The ECM has captivated a great deal of attention with the rapid progress of tissue engineering (TE) in the field of regenerative medicine (RM). Approaches to TE, RM and cancer therapy center on the necessity to deliver cell signals to direct cell proliferation and differentiation. These "external signals" are induced from cell-cell, and cell-ECM, interactions, as well as from physico-chemical, mechanical stimuli and growth factors. With the advent of new biomaterials such as casein, we gave a general insight into cell-ECM protein interactions in biomaterials and their applications in TE, RM and cancer therapy. An account of the main ECM molecules and cellular receptors with emphasis on integrins and its ligands was given, their effect on the induction of particular signal transduction pathways is also elucidated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. One-Dimensional RuO2/Mn2O3 Hollow Architectures as Efficient Bifunctional Catalysts for Lithium-Oxygen Batteries.

    PubMed

    Yoon, Ki Ro; Lee, Gil Yong; Jung, Ji-Won; Kim, Nam-Hoon; Kim, Sang Ouk; Kim, Il-Doo

    2016-03-09

    Rational design and massive production of bifunctional catalysts with fast oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics are critical to the realization of highly efficient lithium-oxygen (Li-O2) batteries. Here, we first exploit two types of double-walled RuO2 and Mn2O3 composite fibers, i.e., (i) phase separated RuO2/Mn2O3 fiber-in-tube (RM-FIT) and (ii) multicomposite RuO2/Mn2O3 tube-in-tube (RM-TIT), by controlling ramping rate during electrospinning process. Both RM-FIT and RM-TIT exhibited excellent bifunctional electrocatalytic activities in alkaline media. The air electrodes using RM-FIT and RM-TIT showed enhanced overpotential characteristics and stable cyclability over 100 cycles in the Li-O2 cells, demonstrating high potential as efficient OER and ORR catalysts.

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

    Hirano, Teruyuki; Suto, Yasushi; Taruya, Atsushi

    We obtain analytical expressions for the velocity anomaly due to the Rossiter-McLaughlin (RM) effect, for the case when the anomalous radial velocity is obtained by cross-correlation with a stellar template spectrum. In the limit of vanishing width of the stellar absorption lines, our result reduces to the formula derived by Ohta et al., which is based on the first moment of distorted stellar lines. Our new formula contains a term dependent on the stellar line width, which becomes important when rotational line broadening is appreciable. We generate mock transit spectra for four existing exoplanetary systems (HD 17156, TrES-2, TrES-4, andmore » HD 209458) following the procedure of Winn et al., and find that the new formula is in better agreement with the velocity anomaly extracted from the mock data. Thus, our result provides a more reliable analytical description of the velocity anomaly due to the RM effect, and explains the previously observed dependence of the velocity anomaly on the stellar rotation velocity.« less

  7. Genetic Dissection of Root Morphological Traits Related to Nitrogen Use Efficiency in Brassica napus L. under Two Contrasting Nitrogen Conditions

    PubMed Central

    Wang, Jie; Dun, Xiaoling; Shi, Jiaqin; Wang, Xinfa; Liu, Guihua; Wang, Hanzhong

    2017-01-01

    As the major determinant for nutrient uptake, root system architecture (RSA) has a massive impact on nitrogen use efficiency (NUE). However, little is known the molecular control of RSA as related to NUE in rapeseed. Here, a rapeseed recombinant inbred line population (BnaZNRIL) was used to investigate root morphology (RM, an important component for RSA) and NUE-related traits under high-nitrogen (HN) and low-nitrogen (LN) conditions by hydroponics. Data analysis suggested that RM-related traits, particularly root size had significantly phenotypic correlations with plant dry biomass and N uptake irrespective of N levels, but no or little correlation with N utilization efficiency (NUtE), providing the potential to identify QTLs with pleiotropy or specificity for RM- and NUE-related traits. A total of 129 QTLs (including 23 stable QTLs, which were repeatedly detected at least two environments or different N levels) were identified and 83 of them were integrated into 22 pleiotropic QTL clusters. Five RM-NUE, ten RM-specific and three NUE-specific QTL clusters with same directions of additive-effect implied two NUE-improving approaches (RM-based and N utilization-based directly) and provided valuable genomic regions for NUE improvement in rapeseed. Importantly, all of four major QTLs and most of stable QTLs (20 out of 23) detected here were related to RM traits under HN and/or LN levels, suggested that regulating RM to improve NUE would be more feasible than regulating N efficiency directly. These results provided the promising genomic regions for marker-assisted selection on RM-based NUE improvement in rapeseed. PMID:29033971

  8. Estimations of One Repetition Maximum and Isometric Peak Torque in Knee Extension Based on the Relationship Between Force and Velocity.

    PubMed

    Sugiura, Yoshito; Hatanaka, Yasuhiko; Arai, Tomoaki; Sakurai, Hiroaki; Kanada, Yoshikiyo

    2016-04-01

    We aimed to investigate whether a linear regression formula based on the relationship between joint torque and angular velocity measured using a high-speed video camera and image measurement software is effective for estimating 1 repetition maximum (1RM) and isometric peak torque in knee extension. Subjects comprised 20 healthy men (mean ± SD; age, 27.4 ± 4.9 years; height, 170.3 ± 4.4 cm; and body weight, 66.1 ± 10.9 kg). The exercise load ranged from 40% to 150% 1RM. Peak angular velocity (PAV) and peak torque were used to estimate 1RM and isometric peak torque. To elucidate the relationship between force and velocity in knee extension, the relationship between the relative proportion of 1RM (% 1RM) and PAV was examined using simple regression analysis. The concordance rate between the estimated value and actual measurement of 1RM and isometric peak torque was examined using intraclass correlation coefficients (ICCs). Reliability of the regression line of PAV and % 1RM was 0.95. The concordance rate between the actual measurement and estimated value of 1RM resulted in an ICC(2,1) of 0.93 and that of isometric peak torque had an ICC(2,1) of 0.87 and 0.86 for 6 and 3 levels of load, respectively. Our method for estimating 1RM was effective for decreasing the measurement time and reducing patients' burden. Additionally, isometric peak torque can be estimated using 3 levels of load, as we obtained the same results as those reported previously. We plan to expand the range of subjects and examine the generalizability of our results.

  9. Effects of ray profile modeling on resolution recovery in clinical CT

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

    Hofmann, Christian; Knaup, Michael; Kachelrieß, Marc, E-mail: marc.kachelriess@dkfz-heidelberg.de

    2014-02-15

    Purpose: Iterative image reconstruction gains more and more interest in clinical routine, as it promises to reduce image noise (and thereby patient dose), to reduce artifacts, or to improve spatial resolution. However, among vendors and researchers, there is no consensus of how to best achieve these goals. The authors are focusing on the aspect of geometric ray profile modeling, which is realized by some algorithms, while others model the ray as a straight line. The authors incorporate ray-modeling (RM) in nonregularized iterative reconstruction. That means, instead of using one simple single needle beam to represent the x-ray, the authors evaluatemore » the double integral of attenuation path length over the finite source distribution and the finite detector element size in the numerical forward projection. Our investigations aim at analyzing the resolution recovery (RR) effects of RM. Resolution recovery means that frequencies can be recovered beyond the resolution limit of the imaging system. In order to evaluate, whether clinical CT images can benefit from modeling the geometrical properties of each x-ray, the authors performed a 2D simulation study of a clinical CT fan-beam geometry that includes the precise modeling of these geometrical properties. Methods: All simulations and reconstructions are performed in native fan-beam geometry. A water phantom with resolution bar patterns and a Forbild thorax phantom with circular resolution patterns representing calcifications in the heart region are simulated. An FBP reconstruction with a Ram–Lak kernel is used as a reference reconstruction. The FBP is compared to iterative reconstruction techniques with and without RM: An ordered subsets convex (OSC) algorithm without any RM (OSC), an OSC where the forward projection is modeled concerning the finite focal spot and detector size (OSC-RM) and an OSC with RM and with a matched forward and backprojection pair (OSC-T-RM, T for transpose). In all cases, noise was matched to be able to focus on comparing spatial resolution. The authors use two different simulation settings. Both are based on the geometry of a typical clinical CT system (0.7 mm detector element size at isocenter, 1024 projections per rotation). Setting one has an exaggerated source width of 5.0 mm. Setting two has a realistically small source width of 0.5 mm. The authors also investigate the transition from setting one to two. To quantify image quality, the authors analyze line profiles through the resolution patterns to define a contrast factor (CF) for contrast-resolution plots, and the authors compare the normalized cross-correlation (NCC) with respect to the ground truth of the circular resolution patterns. To independently analyze whether RM is of advantage, the authors implemented several iterative reconstruction algorithms: The statistical iterative reconstruction algorithm OSC, the ordered subsets simultaneous algebraic reconstruction technique (OSSART) and another statistical iterative reconstruction algorithm, denoted with ordered subsets maximum likelihood (OSML) algorithm. All algorithms were implemented both without RM (denoted as OSC, OSSART, and OSML) and with RM (denoted as OSC-RM, OSSART-RM, and OSML-RM). Results: For the unrealistic case of a 5.0 mm focal spot the CF can be improved by a factor of two due to RM: the 4.2 LP/cm bar pattern, which is the first bar pattern that cannot be resolved without RM, can be easily resolved with RM. For the realistic case of a 0.5 mm focus, all results show approximately the same CF. The NCC shows no significant dependency on RM when the source width is smaller than 2.0 mm (as in clinical CT). From 2.0 mm to 5.0 mm focal spot size increasing improvements can be observed with RM. Conclusions: Geometric RM in iterative reconstruction helps improving spatial resolution, if the ray cross-section is significantly larger than the ray sampling distance. In clinical CT, however, the ray is not much thicker than the distance between neighboring ray centers, as the focal spot size is small and detector crosstalk is negligible, due to reflective coatings between detector elements. Therefore,RM appears not to be necessary in clinical CT to achieve resolution recovery.« less

  10. The potential role of telocytes in Tissue Engineering and Regenerative Medicine.

    PubMed

    Boos, Anja M; Weigand, Annika; Brodbeck, Rebekka; Beier, Justus P; Arkudas, Andreas; Horch, Raymund E

    2016-07-01

    Research and ideas for potential applications in the field of Tissue Engineering (TE) and Regenerative Medicine (RM) have been constantly increasing over recent years, basically driven by the fundamental human dream of repairing and regenerating lost tissue and organ functions. The basic idea of TE is to combine cells with putative stem cell properties with extracellular matrix components, growth factors and supporting matrices to achieve independently growing tissue. As a side effect, in the past years, more insights have been gained into cell-cell interaction and how to manipulate cell behavior. However, to date the ideal cell source has still to be found. Apart from commonly known various stem cell sources, telocytes (TC) have recently attracted increasing attention because they might play a potential role for TE and RM. It becomes increasingly evident that TC provide a regenerative potential and act in cellular communication through their network-forming telopodes. While TE in vitro experiments can be the first step, the key for elucidating their regenerative role will be the investigation of the interaction of TC with the surrounding tissue. For later clinical applications further steps have to include an upscaling process of vascularization of engineered tissue. Arteriovenous loop models to vascularize such constructs provide an ideal platform for preclinical testing of future therapeutic concepts in RM. The following review article should give an overview of what is known so far about the potential role of TC in TE and RM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. A RELATION BETWEEN THE WARM NEUTRAL AND IONIZED MEDIA OBSERVED IN THE CANADIAN GALACTIC PLANE SURVEY

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

    Foster, T.; Kothes, R.; Brown, J. C., E-mail: Tyler.Foster@nrc-cnrc.gc.ca

    2013-08-10

    We report on a comparison between 21 cm rotation measure (RM) and the optically thin atomic hydrogen column density (N{sub H{sub I}}({tau} {yields} 0)) measured toward unresolved extragalactic sources in the Galactic plane of the northern sky. H I column densities integrated to the Galactic edge are measured immediately surrounding each of nearly 2000 sources in 1 arcmin 21 cm line data, and are compared to RMs observed from polarized emission of each source. RM data are binned in column density bins 4 Multiplication-Sign 10{sup 20} cm{sup -2} wide, and one observes a strong relationship between the number of hydrogenmore » atoms in a 1 cm{sup 2} column through the plane and the mean RM along the same line of sight and path length. The relationship is linear over one order of magnitude (from 0.8 to 14 Multiplication-Sign 10{sup 21} atoms cm{sup -2}) of column densities, with a constant RM/N{sub H{sub I}}{approx} -23.2 {+-} 2.3 rad m{sup -2}/10{sup 21} atoms cm{sup -2}, and a positive RM of 45.0 {+-} 13.8 rad m{sup -2} in the presence of no atomic hydrogen. This slope is used to calculate a mean volume-averaged magnetic field in the second quadrant of (B{sub Parallel-To }) {approx}1.0 {+-} 0.1 {mu}G directed away from the Sun, assuming an ionization fraction of 8% (consistent with the warm-neutral medium; WNM). The remarkable consistency between this field and (B) = 1.2 {mu}G found with the same RM sources and a Galactic model of dispersion measures (DMs) suggests that electrons in the partially ionized WNM are mainly responsible for pulsar DMs, and thus the partially ionized WNM is the dominant form of the magneto-ionic interstellar medium.« less

  12. Sinorhizobium meliloti strains TII7 and A5 by Multilocus Sequence Typing (MLST) have chromsomes identical with Rm1021 and form an effective and ineffective symbiosis with Medicago truncatula line Jemalong A17, respectively

    USDA-ARS?s Scientific Manuscript database

    The strains TII7 and A5 formed an effective and ineffective symbiosis with Medicago truncatula Jemalong A17, respectively. Both were shown to have identical chromsomes with strains Rm1021 and RCR2011 using a Multilocus Sequence Typing method. The 2260 bp segments of DNA stretching from the 3’ end ...

  13. Relationship Between Selected Strength and Power Assessments to Peak and Average Velocity of the Drive Block in Offensive Line Play.

    PubMed

    Jacobson, Bert H; Conchola, Eric C; Smith, Doug B; Akehi, Kazuma; Glass, Rob G

    2016-08-01

    Jacobson, BH, Conchola, EC, Smith, DB, Akehi, K, and Glass, RG. Relationship between selected strength and power assessments to peak and average velocity of the drive block in offensive line play. J Strength Cond Res 30(8): 2202-2205, 2016-Typical strength training for football includes the squat and power clean (PC) and routinely measured variables include 1 repetition maximum (1RM) squat and 1RM PC along with the vertical jump (VJ) for power. However, little research exists regarding the association between the strength exercises and velocity of an actual on-the-field performance. The purpose of this study was to investigate the relationship of peak velocity (PV) and average velocity (AV) of the offensive line drive block to 1RM squat, 1RM PC, the VJ, body mass (BM), and body composition. One repetition maximum assessments for the squat and PC were recorded along with VJ height, BM, and percent body fat. These data were correlated with PV and AV while performing the drive block. Peal velocity and AV were assessed using a Tendo Power and Speed Analyzer as the linemen fired, from a 3-point stance into a stationary blocking dummy. Pearson product analysis yielded significant (p ≤ 0.05) correlations between PV and AV and the VJ, the squat, and the PC. A significant inverse association was found for both PV and AV and body fat. These data help to confirm that the typical exercises recommended for American football linemen is positively associated with both PV and AV needed for the drive block effectiveness. It is recommended that these exercises remain the focus of a weight room protocol and that ancillary exercises be built around these exercises. Additionally, efforts to reduce body fat are recommended.

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

    Russell, H. R.; McDonald, M.; McNamara, B. R.

    We report new ALMA observations of the CO(3-2) line emission from themore » $$2.1\\pm0.3\\times10^{10}\\rm\\thinspace M_{\\odot}$$ molecular gas reservoir in the central galaxy of the Phoenix cluster. The cold molecular gas is fuelling a vigorous starburst at a rate of $$500-800\\rm\\thinspace M_{\\odot}\\rm\\; yr^{-1}$$ and powerful black hole activity in the form of both intense quasar radiation and radio jets. The radio jets have inflated huge bubbles filled with relativistic plasma into the hot, X-ray atmospheres surrounding the host galaxy. The ALMA observations show that extended filaments of molecular gas, each $$10-20\\rm\\; kpc$$ long with a mass of several billion solar masses, are located along the peripheries of the radio bubbles. The smooth velocity gradients and narrow line widths along each filament reveal massive, ordered molecular gas flows around each bubble, which are inconsistent with gravitational free-fall. The molecular clouds have been lifted directly by the radio bubbles, or formed via thermal instabilities induced in low entropy gas lifted in the updraft of the bubbles. These new data provide compelling evidence for close coupling between the radio bubbles and the cold gas, which is essential to explain the self-regulation of feedback. As a result, the very feedback mechanism that heats hot atmospheres and suppresses star formation may also paradoxically stimulate production of the cold gas required to sustain feedback in massive galaxies.« less

  15. Frenolicins C-G, pyranonaphthoquinones from Streptomyces sp. RM-4-15.

    PubMed

    Wang, Xiachang; Shaaban, Khaled A; Elshahawi, Sherif I; Ponomareva, Larissa V; Sunkara, Manjula; Zhang, Yinan; Copley, Gregory C; Hower, James C; Morris, Andrew J; Kharel, Madan K; Thorson, Jon S

    2013-08-23

    Appalachian active coal fire sites were selected for the isolation of bacterial strains belonging to the class actinobacteria. A comparison of high-resolution electrospray ionization mass spectrometry (HRESIMS) and ultraviolet (UV) absorption profiles from isolate extracts to natural product databases suggested Streptomyces sp. RM-4-15 to produce unique metabolites. Four new pyranonaphthoquinones, frenolicins C-F (1-4), along with three known analogues, frenolicin (6), frenolicin B (7), and UCF76-A (8), were isolated from the fermentation of this strain. An additional new analogue, frenolicin G (5), along with two known compounds, deoxyfrenolicin (9) and UCF 13 (10), were isolated from the fermentation supplied with 18 mg/L of scandium chloride, the first example, to the best of our knowledge, wherein scandium chloride supplementation led to the confirmed production of new bacterial secondary metabolites. Structures 1-5 were elucidated on the basis of spectral analysis and chemical modification. While frenolicins are best known for their anticoccidial activity, the current study revealed compounds 6-9 to exhibit moderate cytotoxicity against the human lung carcinoma cell line (A549) and thereby extends the anticancer SAR for this privileged scaffold.

  16. Implication of STARD5 and cholesterol homeostasis disturbance in the endoplasmic reticulum stress-related response induced by pro-apoptotic aminosteroid RM-133.

    PubMed

    Perreault, Martin; Maltais, René; Kenmogne, Lucie Carolle; Létourneau, Danny; LeHoux, Jean-Guy; Gobeil, Stéphane; Poirier, Donald

    2018-02-01

    The aminosteroid derivative RM-133 is an effective anticancer molecule for which proof of concept has been achieved in several mouse xenograph models (HL-60, MCF-7, PANC-1 and OVCAR-3). To promote this new family of molecules toward a clinical phase 1 trial, the mechanism of action governing the anticancer properties of the representative candidate RM-133 needs to be characterized. In vitro experiments were first used to determine that RM-133 causes apoptosis in cancer cells. Then, using proteomic and transcriptomic experiments, RM-133 cytotoxicity was proven to be achieved via the endoplasmic reticulum (ER)-related apoptosis, which characterizes RM-133 as an endoplasmic reticulum stress aggravator (ERSA) anticancer drug. Furthermore, an shRNA-genome-wide screening has permitted to identify the steroidogenic acute regulator-related lipid transfer protein 5 (STARD5) as a major player in the RM-133 ER-related apoptosis mechanism, which was validated by an in vitro binding experiment. Altogether, the results presented herein suggest that RM-133 provokes a disturbance of cholesterol homeostasis via the implication of STARD5, which delivers an ERSA molecule to the ER. These results will be a springboard for RM-133 in its path toward clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells.

    PubMed

    Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D; Dyring-Andersen, Beatrice; Agerbeck, Christina; Nielsen, Morten M; Poulsen, Steen S; Woetmann, Anders; Ødum, Niels; Thomsen, Allan R; Geisler, Carsten; Bonefeld, Charlotte M

    2017-04-01

    Skin-resident memory T (T RM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore, the mechanisms whereby T RM cells induce rapid recall responses need further investigation. To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. To address these questions, we analysed responses to contact allergens in mice and humans sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. Challenge responses in both mice and humans were dramatically increased at sites previously exposed to allergens as compared with previously unexposed sites. Importantly, the magnitude of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)-γ-producing T RM cells. Moreover, IL-17A and IFN-γ enhanced allergen-induced IL-1β production in keratinocytes. We show that sensitization with contact allergens induces a strong, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8 + T RM cells. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research and Regenerative Medicine Between the Public and the Scientific Community.

    PubMed

    Shineha, Ryuma; Inoue, Yusuke; Ikka, Tsunakuni; Kishimoto, Atsuo; Yashiro, Yoshimi

    2018-02-01

    Owing to the rapid progress in stem cell research (SCR) and regenerative medicine (RM), society's expectation and interest in these fields are increasing. For effective communication on issues concerning SCR and RM, surveys for understanding the interests of stakeholders is essential. For this purpose, we conducted a large-scale survey with 2,160 public responses and 1,115 responses from the member of the Japanese Society for Regenerative Medicine. Results showed that the public is more interested in the post-realization aspects of RM, such as cost of care, countermeasures for risks and accidents, and clarification of responsibility and liability, than in the scientific aspects; the latter is of greater interest only to scientists. Our data indicate that an increased awareness about RM-associated social responsibility and regulatory framework is required among scientists, such as those regarding its benefits, potential accidents, abuse, and other social consequences. Awareness regarding the importance of communication and education for scientists are critical to bridge the gaps in the interests of the public and scientists. Stem Cells Translational Medicine 2018;7:251-257. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  19. Reference Manual on Interference Seals and Connectors for Undersea Electrical Applications

    DTIC Science & Technology

    1976-07-01

    processes. It has a standard line of metal shell connectors, the ER and EB series, which are available with braided and laced harnass work and breakouts, and...Assemblies (RM) 4-10 4.3.2 Molded Plastic Assemblies (PM) 4-11 4.3.3 Metal Shell Assemblies (MS) 4-12 4.3.4 Pressure-balanced Oil-filled Assemblies...connectors according to material composition. The classes of connectors include: Rubber Molded (RM), Plastic Molded (PM), Metal Shell (MS), Pressure-Balanced

  20. a New Value for the Rydberg Constant by Precision Measurement of the Hydrogen Balmer-Beta Transition.

    NASA Astrophysics Data System (ADS)

    Zhao, Ping

    The Rydberg constant {rm R }_infty is determined to a very high accuracy of 3 parts in 10^{10 } by a direct comparison of the four hydrogen and deuterium Balmer-beta transitions with a standard laser from the National Bureau of Standards. This experiment is now the most precise measurement for {rm R}_infty and approaches the limits of accuracy for wavelength or frequency measurements in the visible region. The result is {rm R}_infty = 109 737.315 73 (3) {rm cm}^{-1} with the definition of the meter: c = 299 792 458 m/sec. The experiment also yields the following results: The fine structure splittings 4{rm P}_ {1/2} rightarrow {rm 4P}_{3/2} in H: 1370.9 (3) MHz and in D: 1371.8 (3) MHz. The isotope shifts between H and D in the transitions {rm 2S}_{1/2} rightarrow {rm 4P}_{1/2}: 167 752.4 (3) MHz and {rm 2S}_{1/2 } rightarrow {rm 4P}_{3/2}: 167 753.3 (3) MHz. The experiment utilizes atomic beam laser spectroscopy. A beam of atomic hydrogen (or deuterium) is excited by electron bombardment to the metastable {rm 2S }_{1/2} state and is detected by a secondary electron emission detector. A chopped cw dye laser beam crosses the atomic beam at an angle of 90^circ to eliminate Doppler broadening. The metastables are quenched by laser excitation to {rm 4P}_{1/2} or {rm 4P}_{3/2 } states. The signal is monitored by a lock -in amplifier with the chopper as reference. An iodine (^{127}{ rm I}_2) stabilized helium-neon (He-Ne) laser is the primary standard with an accuracy of 1.6 times 10^{ -10}. Another He-Ne laser is locked to the standard laser with a variable offset frequency controlled by an oscillator. A frequency chain is established by locking together a dye laser, a piezoelectrically controlled measuring etalon and the offset laser. This chain allows the dye laser to scan across the Balmer-beta line in a precisely controllable manner. The lineshape and offset frequency are recorded simultaneously. Possible sources of systematic shifts and errors are carefully investigated. Hydrogen energy levels are calculated according to most recent values of physical constants. {rm R}_infty is obtained by comparing the measured and calculated hydrogen Balmer-beta transition. The result is in good agreement with the two most recent, but less precise experiments.

  1. Rhizobium meliloti lipooligosaccharide nodulation factors: different structural requirements for bacterial entry into target root hair cells and induction of plant symbiotic developmental responses.

    PubMed

    Ardourel, M; Demont, N; Debellé, F; Maillet, F; de Billy, F; Promé, J C; Dénarié, J; Truchet, G

    1994-10-01

    Rhizobium meliloti produces lipochitooligosaccharide nodulation NodRm factors that are required for nodulation of legume hosts. NodRm factors are O-acetylated and N-acylated by specific C16-unsaturated fatty acids. nodL mutants produce non-O-acetylated factors, and nodFE mutants produce factors with modified acyl substituents. Both mutants exhibited a significantly reduced capacity to elicit infection thread (IT) formation in alfalfa. However, once initiated, ITs developed and allowed the formation of nitrogen-fixing nodules. In contrast, double nodF/nodL mutants were unable to penetrate into legume hosts and to form ITs. Nevertheless, these mutants induced widespread cell wall tip growth in trichoblasts and other epidermal cells and were also able to elicit cortical cell activation at a distance. NodRm factor structural requirements are thus clearly more stringent for bacterial entry than for the elicitation of developmental plant responses.

  2. Stem Cells for Osteochondral Regeneration.

    PubMed

    Canadas, Raphaël F; Pirraco, Rogério P; Oliveira, J Miguel; Reis, Rui L; Marques, Alexandra P

    2018-01-01

    Stem cell research plays a central role in the future of medicine, which is mainly dependent on the advances on regenerative medicine (RM), specifically in the disciplines of tissue engineering (TE) and cellular therapeutics. All RM strategies depend upon the harnessing, stimulation, or guidance of endogenous developmental or repair processes in which cells have an important role. Among the most clinically challenging disorders, cartilage degeneration, which also affects subchondral bone becoming an osteochondral (OC) defect, is one of the most demanding. Although primary cells have been clinically applied, stem cells are currently seen as the promising tool of RM-related research because of its availability, in vitro proliferation ability, pluri- or multipotency, and immunosuppressive features. Being the OC unit, a transition from the bone to cartilage, mesenchymal stem cells (MSCs) are the main focus for OC regeneration. Promising alternatives, which can also be obtained from the patient or at banks and have great differentiation potential toward a wide range of specific cell types, have been reported. Still, ethical concerns and tumorigenic risk are currently under discussion and assessment. In this book chapter, we revise the existing stem cell-based approaches for engineering bone and cartilage, focusing on cell therapy and TE. Furthermore, 3D OC composites based on cell co-cultures are described. Finally, future directions and challenges still to be faced are critically discussed.

  3. New restriction enzymes discovered from Escherichia coli clinical strains using a plasmid transformation method

    PubMed Central

    Kasarjian, Julie K. A.; Iida, Masatake; Ryu, Junichi

    2003-01-01

    The presence of restriction enzymes in bacterial cells has been predicted by either classical phage restriction-modification (R-M) tests, direct in vitro enzyme assays or more recently from bacterial genome sequence analysis. We have applied phage R-M test principles to the transformation of plasmid DNA and established a plasmid R-M test. To validate this test, six plasmids that contain BamHI fragments of phage lambda DNA were constructed and transformed into Escherichia coli strains containing known R-M systems including: type I (EcoBI, EcoAI, Eco124I), type II (HindIII) and type III (EcoP1I). Plasmid DNA with a single recognition site showed a reduction of relative efficiency of transformation (EOT = 10–1–10–2). When multiple recognition sites were present, greater reductions in EOT values were observed. Once established in the cell, the plasmids were subjected to modification (EOT = 1.0). We applied this test to screen E.coli clinical strains and detected the presence of restriction enzymes in 93% (14/15) of cells. Using additional subclones and the computer program, RM Search, we identified four new restriction enzymes, Eco377I, Eco585I, Eco646I and Eco777I, along with their recognition sequences, GGA(8N)ATGC, GCC(6N)TGCG, CCA(7N)CTTC, and GGA(6N)TATC, respectively. Eco1158I, an isoschizomer of EcoBI, was also found in this study. PMID:12595571

  4. Alma observations of massive molecular gas filaments encasing radio bubbles in the Phoenix cluster

    DOE PAGES

    Russell, H. R.; McDonald, M.; McNamara, B. R.; ...

    2017-02-14

    We report new ALMA observations of the CO(3-2) line emission from themore » $$2.1\\pm0.3\\times10^{10}\\rm\\thinspace M_{\\odot}$$ molecular gas reservoir in the central galaxy of the Phoenix cluster. The cold molecular gas is fuelling a vigorous starburst at a rate of $$500-800\\rm\\thinspace M_{\\odot}\\rm\\; yr^{-1}$$ and powerful black hole activity in the form of both intense quasar radiation and radio jets. The radio jets have inflated huge bubbles filled with relativistic plasma into the hot, X-ray atmospheres surrounding the host galaxy. The ALMA observations show that extended filaments of molecular gas, each $$10-20\\rm\\; kpc$$ long with a mass of several billion solar masses, are located along the peripheries of the radio bubbles. The smooth velocity gradients and narrow line widths along each filament reveal massive, ordered molecular gas flows around each bubble, which are inconsistent with gravitational free-fall. The molecular clouds have been lifted directly by the radio bubbles, or formed via thermal instabilities induced in low entropy gas lifted in the updraft of the bubbles. These new data provide compelling evidence for close coupling between the radio bubbles and the cold gas, which is essential to explain the self-regulation of feedback. As a result, the very feedback mechanism that heats hot atmospheres and suppresses star formation may also paradoxically stimulate production of the cold gas required to sustain feedback in massive galaxies.« less

  5. Six Sigma methods applied to cryogenic coolers assembly line

    NASA Astrophysics Data System (ADS)

    Ventre, Jean-Marc; Germain-Lacour, Michel; Martin, Jean-Yves; Cauquil, Jean-Marc; Benschop, Tonny; Griot, René

    2009-05-01

    Six Sigma method have been applied to manufacturing process of a rotary Stirling cooler: RM2. Name of the project is NoVa as main goal of the Six Sigma approach is to reduce variability (No Variability). Project has been based on the DMAIC guideline following five stages: Define, Measure, Analyse, Improve, Control. Objective has been set on the rate of coolers succeeding performance at first attempt with a goal value of 95%. A team has been gathered involving people and skills acting on the RM2 manufacturing line. Measurement System Analysis (MSA) has been applied to test bench and results after R&R gage show that measurement is one of the root cause for variability in RM2 process. Two more root causes have been identified by the team after process mapping analysis: regenerator filling factor and cleaning procedure. Causes for measurement variability have been identified and eradicated as shown by new results from R&R gage. Experimental results show that regenerator filling factor impacts process variability and affects yield. Improved process haven been set after new calibration process for test bench, new filling procedure for regenerator and an additional cleaning stage have been implemented. The objective for 95% coolers succeeding performance test at first attempt has been reached and kept for a significant period. RM2 manufacturing process is now managed according to Statistical Process Control based on control charts. Improvement in process capability have enabled introduction of sample testing procedure before delivery.

  6. Molecular mapping and genetic analysis of a rice brown planthopper (Nilaparvata lugens Stål) resistance gene.

    PubMed

    Yang, Haiyuan; Ren, Xiang; Weng, Qingmei; Zhu, Lili; He, Guangcun

    2002-01-01

    The brown planthopper (BPH), Nilaparvata lugens Stål, is a serious insect pest of rice (Oryza saliva L.). We have determined the chromosomal location of a BPH resistance gene in rice using SSR and RFLP techniques. A rice line 'B14', derived from the wild rice Oryza latifolia, showed high resistance to BPH. For tagging the resistance gene in 'B14X', an F2 population and a recombinant inbred (RI) population from a cross between Taichung Native 1 and 'B14' were developed and evaluated for BPH resistance. The results showed that a single dominant gene controlled the resistance of 'B14' to BPH. Bulked segregant SSR analysis was employed for identification of DNA markers linked to the resistance gene. From the survey of 302 SSR primer pairs, three SSR (RM335, RM261, RM185) markers linked to the resistance gene were identified. The closest SSR marker RM261 was linked to the resistance gene at a distance of 1.8 cM. Regions surrounding the resistance gene and the SSR markers were examined with additional RFLP markers on chromosome 4 to define the location of the resistance gene. Linkage of RFLP markers C820, R288, C946 with the resistance gene further confirmed its location on the short arm of chromosome 4. Closely linked DNA markers will facilitate selection for resistant lines in breeding programs and provide the basis for map-based cloning of this resistance gene.

  7. Nutrients, Antioxidant Capacity and Safety of Hot Water Extract from Sugar Maple (Acer saccharum M.) and Red Maple (Acer rubrum L.) Bark.

    PubMed

    Bhatta, Sagar; Ratti, Cristina; Poubelle, Patrice E; Stevanovic, Tatjana

    2018-03-01

    Sugar maple (Acer saccharum M.) and red maple (Acer rubrum L.) barks were treated with hot water to extract nutrients in order to explore, for the first time, its potential as safe dietary antioxidants. The organic and inorganic nutrients of these extracts, as well as their safety on human PLB-985 cells differentiated into neutrophils-like cells, were determined. Proximate analysis showed that both bark extracts were low in moisture and fat. Sugar maple bark extract (SM-BX) showed crude protein and ash content higher than those found in red maple bark extract (RM-BX). In addition, SM-BX had total sugars higher than those evaluated in RM-BX, while complex sugars (oligo- and/or poly-saccharides) were similarly abundant in both bark extracts. Furthermore, SM-BX demonstrated a wide array of vital minerals (K, Ca, Mg, P, Na, Fe and Cu) in quantity larger than that evaluated in RM-BX, whereas RM-BX have Zn and Mn levels higher than those found in SM-BX. Phytochemical analyses showed that RM-BX exhibited total phenolic and flavonoid contents higher than those measured in SM-BX. Consequently, RM-BX presented an antioxidant activity higher than that of SM-BX: 2.85-fold ABTS radical cation scavenging capacity and 1.9-fold oxygen radical absorbance capacity. Finally, RM-BX and SM-BX were greatly safe since, at concentration up to 100 μg/ml, they did not modify the viability of neutrophils as determined by flow-cytometry assay using Annexin V-FITC/Propidum Iodide as markers. In conclusion, our in vitro studies indicate that both red and sugar maple bark extracts have a real potential as food additives.

  8. The Correlated Variations of {\\rm{C}}\\,{\\rm{IV}} Narrow Absorption Lines and Quasar Continuum

    NASA Astrophysics Data System (ADS)

    Chen, Zhi-Fu; Pang, Ting-Ting; He, Bing; Huang, Yong

    2018-06-01

    We assemble 207 variable quasars from the Sloan Digital Sky Survey, all with at least 3 observations, to analyze C IV narrow absorption doublets, and obtain 328 C IV narrow absorption line systems. We find that 19 out of 328 C IV narrow absorption line systems were changed by | {{Δ }}{W}rλ 1548| ≥slant 3{σ }{{Δ }{W}rλ 1548} on timescales from 15.9 to 1477 days at rest-frame. Among the 19 obviously variable C IV systems, we find that (1) 14 systems have relative velocities {\\upsilon }r> 0.01c and 4 systems have {\\upsilon }r> 0.1c, where c is the speed of light; (2) 13 systems are accompanied by other variable C IV systems; (3) 9 systems were changed continuously during multiple observations; and (4) 1 system with {\\upsilon }r = 16,862 km s‑1 was enhanced by {{Δ }}{W}rλ 1548=2.7{σ }{{Δ }{W}rλ 1548} in 0.67 day at rest-frame. The variations of absorption lines are inversely correlated with the changes in the ionizing continuum. We also find that large variations of C IV narrow absorption lines are form differently over a short timescale.

  9. Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer.

    PubMed

    Ding, Hui; Lv, Yanlin; Ni, Dezhi; Wang, Jie; Tian, Zhiyuan; Wei, Wei; Ma, Guanghui

    2015-06-07

    A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.

  10. L'effet Hall Quantique

    NASA Astrophysics Data System (ADS)

    Samson, Thomas

    Nous proposons une methode permettant d'obtenir une expression pour la conductivite de Hall de structures electroniques bidimensionnelles et nous examinons celle -ci a la limite d'une temperature nulle dans le but de verifier l'effet Hall quantique. Nous allons nous interesser essentiellement a l'effet Hall quantique entier et aux effets fractionnaires inferieurs a un. Le systeme considere est forme d'un gaz d'electrons en interaction faible avec les impuretes de l'echantillon. Le modele du gaz d'electrons consiste en un gaz bidimensionnel d'electrons sans spin expose perpendiculairement a un champ magnetique uniforme. Ce dernier est decrit par le potentiel vecteur vec{rm A} defini dans la jauge de Dingle ou jauge symetrique. Conformement au formalisme de la seconde quantification, l'hamiltonien de ce gaz est represente dans la base des etats a un-corps de Dingle |n,m> et exprime ainsi en terme des operateurs de creation et d'annihilation correspondants a_sp{ rm n m}{dag} et a _{rm n m}. Nous supposons de plus que les electrons du niveau fondamental de Dingle interagissent entre eux via le potentiel coulombien. La methode utilisee fait appel a une equation mai tresse a N-corps, de nature quantique et statistique, et verifiant le second principe de la thermodynamique. A partir de celle-ci, nous obtenons un systeme d'equations differentielles appele hierarchie d'equations quantique dont la resolution nous permet de determiner une equation a un-corps, dite de Boltzmann quantique, et dictant l'evolution de la moyenne statistique de l'operateur non-diagonal a _sp{rm n m}{dag } a_{rm n}, _{rm m}, sous l'action du champ electrique applique vec{rm E}(t). C'est sa solution Tr(p(t) a _sp{rm n m}{dag} a_{rm n},_ {rm m}), qui definit la relation de convolution entre la densite courant de Hall vec{rm J}_{rm H }(t) et le champ electrique vec {rm E}(t) dont la transformee de Laplace-Fourier du noyau nous fournit l'expression de la conductivite de Hall desiree. Pour une valeur de facteur d'occupation (nombre d'electrons/degenerescence des etats de Dingle) superieure a un, c'est-a-dire en absence d'interaction electron-electron, il nous sera facile d'evaluer cette conductivite a la limite d'une temperature nulle et de demontrer qu'elle tend vers l'une des valeurs quantiques qe^2/h conformement a l'effet Hall quantique entier. Cependant, pour une valeur du facteur d'occupation inferieure a un, c'est-a-dire en presence d'interaction electron-electron, nous ne pourrons evaluer cette limite et obtenir les resultats escomptes a cause de l'impossibilite de determiner l'un des termes impliques. Neanmoins, ce dernier etant de nature statistique, il pourra etre aisement mis en fonction du propagateur du gaz d'electrons dont on doit maintenant determiner une expression en regime effet Hall quantique fractionnaire. Apres avoir demontre l'impuissance de la theorie des perturbations, basee sur le theoreme de Wick et la technique des diagrammes de Feynman, a accomplir cette tache correctement, nous proposons une seconde methode. Celle -ci fait appel au formalisme de l'integrale fonctionnelle et a l'utilisation d'une transformation de Hubbard-Stratonovich generalisee permettant de substituer a l'interaction a deux-corps une interaction effective a un-corps. L'expression finale obtenue bien que non completement resolue, devrait pouvoir etre estimee par une bonne approximation analytique ou au pire numeriquement.

  11. Deep multi-frequency rotation measure tomography of the galaxy cluster A2255

    NASA Astrophysics Data System (ADS)

    Pizzo, R. F.; de Bruyn, A. G.; Bernardi, G.; Brentjens, M. A.

    2011-01-01

    Aims: By studying the polarimetric properties of the radio galaxies and the radio filaments belonging to the galaxy cluster Abell 2255, we aim to unveil their 3-dimensional location within the cluster. Methods: We performed WSRT observations of A2255 at 18, 21, 25, 85, and 200 cm. The polarization images of the cluster were processed through rotation measure (RM) synthesis, producing three final RM cubes. Results: The radio galaxies and the filaments at the edges of the halo are detected in the high-frequency RM cube, obtained by combining the data at 18, 21, and 25 cm. Their Faraday spectra show different levels of complexity. The radio galaxies lying near by the cluster center have Faraday spectra with multiple peaks, while those at large distances show only one peak, as do the filaments. Similar RM distributions are observed for the external radio galaxies and for the filaments, with much lower average RM values and RM variance than those found in previous works for the central radio galaxies. The 85 cm RM cube is dominated by the Galactic foreground emission, but it also shows features associated with the cluster. At 2 m, no polarized emission from A2255 nor our Galaxy is detected. Conclusions: The radial trend observed in the RM distributions of the radio galaxies and in the complexity of their Faraday spectra favors the interpretation that the external Faraday screen for all the sources in A2255 is the ICM. Its differential contribution depends on the amount of medium that the radio signal crosses along the line of sight. The filaments should therefore be located at the periphery of the cluster, and their apparent central location comes from projection effects. Their high fractional polarization and morphology suggest that they are relics rather than part of a genuine radio halo. Their inferred large distance from the cluster center and their geometry could argue for an association with large-scale structure (LSS) shocks. The RM cubes in gif format are only available in electronic form at http://www.aanda.org. To request the RM cubes in FITS format, please contact R. F. Pizzo at: pizzo@astron.nl

  12. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

    PubMed Central

    Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

    2015-01-01

    Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

  13. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

    PubMed

    Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

    2015-01-01

    During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

  14. Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

    PubMed

    Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

    2007-04-01

    Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.

  15. Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain.

    PubMed

    Creus, Montserrat; Deulofeu, Ramon; Peñarrubia, Joana; Carmona, Francisco; Balasch, Juan

    2013-03-01

    Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation.

  16. 75 FR 72832 - Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ..., rm. 1061, Rockville, MD 20852. Submit a single copy of electronic comments or a paper copy of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with... committee hot line/phone line to learn about possible modifications before coming to the meeting. Agenda: On...

  17. VizieR Online Data Catalog: SDSS-RM project: peak velocities of QSOs (Shen+, 2016)

    NASA Astrophysics Data System (ADS)

    Shen, Y.; Brandt, W. N.; Richards, G. T.; Denney, K. D.; Greene, J. E.; Grier, C. J.; Ho, L. C.; Peterson, B. M.; Petitjean, P.; Schneider, D. P.; Tao, C.; Trump, J. R.

    2017-01-01

    The SDSS-RM quasar sample includes 849 broad-line quasars at 0.1

  18. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

    PubMed

    Chow, Laura Q M; Haddad, Robert; Gupta, Shilpa; Mahipal, Amit; Mehra, Ranee; Tahara, Makoto; Berger, Raanan; Eder, Joseph Paul; Burtness, Barbara; Lee, Se-Hoon; Keam, Bhumsuk; Kang, Hyunseok; Muro, Kei; Weiss, Jared; Geva, Ravit; Lin, Chia-Chi; Chung, Hyun Cheol; Meister, Amy; Dolled-Filhart, Marisa; Pathiraja, Kumudu; Cheng, Jonathan D; Seiwert, Tanguy Y

    2016-11-10

    Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC.

  19. How to manage MTTF larger than 30,000hr on rotary cryocoolers

    NASA Astrophysics Data System (ADS)

    Cauquil, Jean-Marc; Seguineau, Cédric; Martin, Jean-Yves; Van-Acker, Sébastien; Benschop, Tonny

    2017-05-01

    The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. Indeed, Stirling coolers are mechanical systems where wear occurs on millimetric mechanisms. The exponential law classically used in electronics for Mean Time to Failure (MTTF) calculation cannot be directly used for mechanical devices. With new applications for thermal sensor like border surveillance, an increasing reliability has become mandatory for rotary cooler. The current needs are above several tens of thousands of continuous hour of cooling. Thales Cryogenics made specific development on that topic, for both linear and rotary applications. The time needed for validating changes in processes through suited experimental design is hardly affordable by following a robust and rigorous standard scientific approach. The targeted Mean Time to Failure (MTTF) led us to adopt an innovative approach to keep development phases in line with expected time to market. This innovative approach is today widespread on all of Thales Cryogenics rotary products and results in a proven increase of MTTF for RM2, RM3 and recently RM1. This paper will then focused on the current MTTF figures measured on RM1, RM2 and RM3. After explaining the limit of a conventional approach, the paper will then describe the current method. At last, the authors will explain how these principles are taken into account for the new SWaP rotary cooler of Thales Cryogénie SAS.

  20. Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines

    PubMed Central

    Lu, Dong-Hong; Guo, Xiao-Yun; Qin, Shan-Yu; Luo, Wei; Huang, Xiao-Li; Chen, Mei; Wang, Jia-Xu; Ma, Shi-Jia; Yang, Xian-Wen; Jiang, Hai-Xing

    2015-01-01

    AIM: To investigate the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved. METHODS: Liver fibrosis was induced in male BALB/c mice by CCl4. Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl4-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of α-smooth muscle actin expression. The frequencies of T helper (Th) 22 cells, Th17 cells and Th1 cells, the expression of inflammatory cytokines [IL-22, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-1β] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORγt), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-γ, TNF-α, IL-6 and IL-1β were evaluated. RESULTS: Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-γ were observed in the hepatic fibrosis group compared with the control group (P < 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis, which was confirmed by lower hepatic fibrosis pathological scores (P < 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% vs 8.09% ± 0.74%, P < 0.01), Th17 cells (4.34% ± 0.37% vs 5.71% ± 0.24%, P < 0.01), Th1 cells (3.09% ± 0.49% vs 4.91% ± 0.73%, P < 0.01), and the levels of IL-22 (56.23 ± 3.08 vs 70.29 ± 3.01, P < 0.01), IL-17A (30.74 ± 2.77 vs 45.68 ± 2.71, P < 0.01), and IFN-γ (74.78 ± 2.61 vs 124.89 ± 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-γ, TNF-α, IL-6, IL-1β, AHR RORγt, and T-bet gene expression in the liver was observed in the rmIL-22 group (P < 0.01). CONCLUSION: The frequencies of Th22, Th17 and Th1 cells are elevated in hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines, thereby ameliorating liver fibrogenesis. PMID:25663772

  1. Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6.

    PubMed

    Shaaban, Khaled A; Saunders, Meredith A; Zhang, Yinan; Tran, Tuan; Elshahawi, Sherif I; Ponomareva, Larissa V; Wang, Xiachang; Zhang, Jianjun; Copley, Gregory C; Sunkara, Manjula; Kharel, Madan K; Morris, Andrew J; Hower, James C; Tremblay, Matthew S; Prendergast, Mark A; Thorson, Jon S

    2017-01-27

    The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6-8] and 11 previously reported bacterial metabolites (1, 3, 9-12a, and 14-18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.

  2. Circulating cell-derived microparticles in women with pregnancy loss.

    PubMed

    Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Farran-Codina, Immaculada; Zarzoso, Cristina; Cabero-Roura, Luis; Vilardell-Tarres, Miquel

    2011-09-01

    To analyze cell-derived microparticles (cMP) in pregnancy loss (PL), both recurrent miscarriages (RM) and unexplained fetal loss (UFL). Non-matched case-control study was performed at Vall d'Hebron Hospital. Cell-derived microparticles of 53 PL cases, 30 with RM, 16 with UFL, and 7 (RM + UFL), were compared to 38 healthy pregnant women. Twenty healthy non-pregnant women act as controls. Cell-derived microparticles were analyzed through flow cytometry. Results are given as total annexin (A5+), endothelial-(CD144+/CD31+ CD41-), platelet-(CD41+), leukocyte-(CD45+) and CD41- c-MP/μL of plasma. Antiphospholipid antibodies (aPLA) were analyzed according to established methods. Comparing PL versus healthy pregnant, we observed a significant endothelial cMP decrease in PL. When comparing RM subgroup with controls, we observed significant decreases in endothelial cMP. When comparing the PL positive for aPLA versus PL-aPLA-negative, no cMP numbering differences were seen. Pregnancy loss seems to be related to endothelial cell activation and/or consumption. A relationship between aPLA and cMP could not be demonstrated. © 2011 John Wiley & Sons A/S.

  3. Understanding AGNs in the Local Universe through Optical Reverberation Mapping

    NASA Astrophysics Data System (ADS)

    Pei, Liuyi

    2016-01-01

    I present the results of observational projects aimed at measuring the mass of the black hole at the center of active galactic nuclei (AGNs) and understanding the structure and kinematics of the broad-line emitting gas within the black hole's sphere of influence.The first project aims to measure the black hole mass in the Kepler-field AGN KA1858. We obtained simultaneous spectroscopic data from the Lick Observatory 3-m telescope using the Kast Double Spectrograph and photometry data from five ground-based telescopes, and used reverberation mapping (RM) techniques to measure the emission-line light curves' lags relative to continuum variations. We obtained lags for H-beta, H-gamma, H-delta, and He II, and obtained the first black hole mass measurement for this object. Our results will serve as a reference point for future studies on relations between black hole mass and continuum variability characteristics using Kepler AGN light curves.The second project, in collaboration with the AGN STORM team, aims to understand the structure and dynamics of the broad line region (BLR) in NGC 5548 in both UV and optical wavelengths. To supplement 6 months of HST UV observations, we obtained simultaneous optical spectroscopic data from six ground-based observatories. We obtained emission-line lags for the optical H-beta and He II lines as well as velocity-resolved lag measurements for H-beta. We also compared the velocity-resolved lags for H-beta to the UV emission lines C IV and Ly-alpha and found similar lag profiles for all three lines.Finally, I will discuss my contributions to two other collaborations in AGN RM. A key component in RM is monitoring continuum variability, which is often done through ground-based photometry. I will present a pipeline that performs aperture photometry on any number of images of an AGN with WCS coordinates and immediately produces relative light curves. This pipeline enables quick looks of AGN variability in real time and has been used in the LAMP 2011 and the LCOGT Key Project collaborations. It is also applicable to large archival datasets in preparation for survey campaigns in the near future.

  4. Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head?

    PubMed

    Janot, M S; Kersting, S; Belyaev, O; Matuschek, A; Chromik, A M; Suelberg, D; Uhl, W; Tannapfel, A; Bergmann, U

    2012-08-01

    According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

  5. The Effects of Ultrasound on Biological Systems: Site

    NASA Astrophysics Data System (ADS)

    El-Karmi, Anan M.

    Earlier studies (Dinno et al., Ultrasound Med. Biol. 15:461 -470; 1989) demonstrated that ultrasound at therapeutic intensities causes large increases in total conductance (G_{rm t}) of frog skin. These changes were attributed to non-thermal mechanisms, primarily, cavitation. In this study, the site(s) and mechanism(s) of action of ultrasound for the increase in G_{rm t} were examined. The reversible changes in G_{rm t } and sodium current were monitored in real time as a function of ultrasound exposure. Amiloride, a sodium channel blocker, was used to differentiate between cellular (G_{rm c}) and paracellular (G_{rm s}) pathways in the presence and absence of ultrasound. No significant changes were detected in G_ {rm c}. However, changes in G _{rm s} were significant. These results demonstrate that most of the increase in G _{rm t} due to ultrasound is taking place in the paracellular pathways. Sodium channels were not significantly affected by ultrasound. Thus, the changes in G_{rm c} are not specific. The effects of ultrasound were examined in the presence of radical scavengers and antioxidants. The increase in G_{rm t} due to ultrasound was significantly minimized in the presence of cystamine, cysteamine, and sodium ascorbate. This demonstrates that free radicals and other reactive species generated by cavitation are causing the increase in G_ {rm t}, possibly by acting from inside the cells. Radical scavengers and antioxidants are providing protection from oxidative damage but are not involved in the recovery of G_{ rm t} towards steady state values after sonication. The role of Ca^{2+} in the effects of ultrasound was examined since many of the cellular reactions involved in tissue recovery are dependent on the intracellular availability of free Ca^{2+}. The percentage increase in G_{rm t} in the presence of Ca^{2+} was larger than in its absence (140% vs. 27%). The time constant for G_{rm t} to return to steady state was longer in calcium-free solutions (122 vs. 18 minutes). This demonstrates that the biological effects of ultrasound are influenced by Ca^ {2+}. The larger increases in G _{rm t} and the time constants confirm other studies addressing the role of Ca ^{2+} in potentiating lipid peroxidation by free radicals, and the role of calcium ions in the formation of tight junctions.

  6. Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.

    PubMed

    Smith, N Ms; Wasserman, G A; Coleman, F T; Hilliard, K L; Yamamoto, K; Lipsitz, E; Malley, R; Dooms, H; Jones, M R; Quinton, L J; Mizgerd, J P

    2018-01-01

    As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4 + cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4 + resident memory T (T RM ) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4 + T RM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4 + T RM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.

  7. Serotonergic raphe magnus cell discharge reflects ongoing autonomic and respiratory activities.

    PubMed

    Mason, Peggy; Gao, Keming; Genzen, Jonathan R

    2007-10-01

    Serotonergic cells are located in a restricted number of brain stem nuclei, send projections to virtually all parts of the CNS, and are critical to normal brain function. They discharge tonically at a rate modulated by the sleep-wake cycle and, in the case of medullary serotonergic cells in raphe magnus and the adjacent reticular formation (RM), are excited by cold challenge. Yet, beyond behavioral state and cold, endogenous factors that influence serotonergic cell discharge remain largely mysterious. The present study in the anesthetized rat investigated predictors of serotonergic RM cell discharge by testing whether cell discharge correlated to three rhythms observed in blood pressure recordings that averaged >30 min in length. A very slow frequency rhythm with a period of minutes, a respiratory rhythm, and a cardiac rhythm were derived from the blood pressure recording. Cross-correlations between each of the derived rhythms and cell activity revealed that the discharge of 38 of the 40 serotonergic cells studied was significantly correlated to the very slow and/or respiratory rhythms. Very few serotonergic cells discharged in relation to the cardiac cycle and those that did, did so weakly. The correlations between serotonergic cell discharge and the slow and respiratory rhythms cannot arise from baroreceptive input. Instead we hypothesize that they are by-products of ongoing adjustments to homeostatic functions that happen to alter blood pressure. Thus serotonergic RM cells integrate information about multiple homeostatic activities and challenges and can consequently modulate spinal processes according to the most pressing need of the organism.

  8. Fitting membrane resistance along with action potential shape in cardiac myocytes improves convergence: application of a multi-objective parallel genetic algorithm.

    PubMed

    Kaur, Jaspreet; Nygren, Anders; Vigmond, Edward J

    2014-01-01

    Fitting parameter sets of non-linear equations in cardiac single cell ionic models to reproduce experimental behavior is a time consuming process. The standard procedure is to adjust maximum channel conductances in ionic models to reproduce action potentials (APs) recorded in isolated cells. However, vastly different sets of parameters can produce similar APs. Furthermore, even with an excellent AP match in case of single cell, tissue behaviour may be very different. We hypothesize that this uncertainty can be reduced by additionally fitting membrane resistance (Rm). To investigate the importance of Rm, we developed a genetic algorithm approach which incorporated Rm data calculated at a few points in the cycle, in addition to AP morphology. Performance was compared to a genetic algorithm using only AP morphology data. The optimal parameter sets and goodness of fit as computed by the different methods were compared. First, we fit an ionic model to itself, starting from a random parameter set. Next, we fit the AP of one ionic model to that of another. Finally, we fit an ionic model to experimentally recorded rabbit action potentials. Adding the extra objective (Rm, at a few voltages) to the AP fit, lead to much better convergence. Typically, a smaller MSE (mean square error, defined as the average of the squared error between the target AP and AP that is to be fitted) was achieved in one fifth of the number of generations compared to using only AP data. Importantly, the variability in fit parameters was also greatly reduced, with many parameters showing an order of magnitude decrease in variability. Adding Rm to the objective function improves the robustness of fitting, better preserving tissue level behavior, and should be incorporated.

  9. Immune clearance of highly pathogenic SIV infection

    PubMed Central

    Hansen, Scott G.; Piatak, Michael; Ventura, Abigail B.; Hughes, Colette M.; Gilbride, Roxanne M.; Ford, Julia C.; Oswald, Kelli; Shoemaker, Rebecca; Li, Yuan; Lewis, Matthew S.; Gilliam, Awbrey N.; Xu, Guangwu; Whizin, Nathan; Burwitz, Benjamin J.; Planer, Shannon L.; Turner, John M.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Früh, Klaus; Sacha, Jonah B.; Estes, Jacob D.; Keele, Brandon F.; Edlefsen, Paul T.; Lifson, Jeffrey D.; Picker, Louis J.

    2013-01-01

    Established infections with the human and simian immunodeficiency viruses (HIV, SIV) are thought to be permanent with even the most effective immune responses and anti-retroviral therapies (ART) only able to control, but not clear, these infections1–4. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that ~50% of rhesus macaques (RM) vaccinated with SIV protein-expressing Rhesus Cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviremic control of infection with highly pathogenic SIVmac2395. Here, we demonstrate that regardless of route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and hematogenous viral dissemination, and that replication-competent SIV persists in multiple sites for weeks to months. However, over time, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma or tissue-associated virus using ultrasensitive assays, and loss of T cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive RT-PCR and PCR analysis of tissues from RhCMV/SIV vector-protected RM necropsied 69–172 weeks after challenge did not detect SIV RNA or DNA over background, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million hematolymphoid cells to naïve RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T cell-mediated immune surveillance elicited and maintained by CMV vectors. PMID:24025770

  10. Immune clearance of highly pathogenic SIV infection.

    PubMed

    Hansen, Scott G; Piatak, Michael; Ventura, Abigail B; Hughes, Colette M; Gilbride, Roxanne M; Ford, Julia C; Oswald, Kelli; Shoemaker, Rebecca; Li, Yuan; Lewis, Matthew S; Gilliam, Awbrey N; Xu, Guangwu; Whizin, Nathan; Burwitz, Benjamin J; Planer, Shannon L; Turner, John M; Legasse, Alfred W; Axthelm, Michael K; Nelson, Jay A; Früh, Klaus; Sacha, Jonah B; Estes, Jacob D; Keele, Brandon F; Edlefsen, Paul T; Lifson, Jeffrey D; Picker, Louis J

    2013-10-03

    Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.

  11. Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

    PubMed Central

    Klatt, Nichole R.; Canary, Lauren A.; Vanderford, Thomas H.; Vinton, Carol L.; Engram, Jessica C.; Dunham, Richard M.; Cronise, Heather E.; Swerczek, Joanna M.; Lafont, Bernard A. P.; Picker, Louis J.; Silvestri, Guido

    2012-01-01

    Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4+ T cell depletion, as CD4+ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression. PMID:22090099

  12. Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques.

    PubMed

    Klatt, Nichole R; Canary, Lauren A; Vanderford, Thomas H; Vinton, Carol L; Engram, Jessica C; Dunham, Richard M; Cronise, Heather E; Swerczek, Joanna M; Lafont, Bernard A P; Picker, Louis J; Silvestri, Guido; Brenchley, Jason M

    2012-01-01

    Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.

  13. Enhanced contrast ratio and viewing angle of polymer-stabilized liquid crystal via refractive index matching between liquid crystal and polymer network.

    PubMed

    Lee, Ji-Hoon; Lee, Jung Jin; Lim, Young Jin; Kundu, Sudarshan; Kang, Shin-Woong; Lee, Seung Hee

    2013-11-04

    Long standing electro-optic problems of a polymer-dispersed liquid crystal (PDLC) such as low contrast ratio and transmittances decrease in oblique viewing angle have been challenged with a mixture of dual frequency liquid crystal (DFLC) and reactive mesogen (RM). The DFLC and RM molecules were vertically aligned and then photo-polymerized using a UV light. At scattering state under 50 kHz electric field, DFLC was switched to planar state, giving greater extraordinary refractive index than the normal PDLC cell. Consequently, the scattering intensity and the contrast ratio were increased compared to the conventional PDLC cell. At transparent state under 1 kHz electric field, the extraordinary refractive index of DFLC was simultaneously matched with the refractive index of vertically aligned RM so that the light scattering in oblique viewing angles was minimized, giving rise to high transmittance in all viewing angles.

  14. The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

    PubMed

    O'Neill, M; Chen, A; Murray, N E

    1997-12-23

    Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

  15. Promissory identities: Sociotechnical representations & innovation in regenerative medicine.

    PubMed

    Gardner, John; Higham, Ruchi; Faulkner, Alex; Webster, Andrew

    2017-02-01

    The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of 'technology identity' and 'development space' to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a 'point-of-care' cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Sexual maturity in growing dinosaurs does not fit reptilian growth models

    PubMed Central

    Lee, Andrew H.; Werning, Sarah

    2008-01-01

    Recent histological studies suggest relatively rapid growth in dinosaurs. However, the timing of reproductive maturity (RM) in dinosaurs is poorly known because unambiguous indicators of RM are rare. One exception is medullary bone (MB), which is an ephemeral bony tissue that forms before ovulation in the marrow cavities of birds as a calcium source for eggshelling. Recently, MB also was described in a single specimen of the saurischian dinosaur Tyrannosaurus rex. Here, we report two other occurrences of MB: in another saurischian dinosaur, Allosaurus, and in the ornithischian dinosaur Tenontosaurus. We show by counting lines of arrested growth and performing growth curve reconstructions that Tenontosaurus, Allosaurus, and Tyrannosaurus were reproductively mature by 8, 10, and 18 years, respectively. RM in these dinosaurs coincided with a transition from growth acceleration to deceleration. It also far precedes predictions based on the growth rates of living reptiles scaled to similar size. Despite relatively rapid growth, dinosaurs were similar to reptiles in that RM developed before reaching asymptotic size. However, this reproductive strategy also occurs in medium- to large-sized mammals and correlates with a strategy of prolonged multiyear growth. RM in actively growing individuals suggests that these dinosaurs were born relatively precocial and experienced high adult mortality. The origin of the modern avian reproductive strategy in ornithuran birds likely coincided with their extreme elevations in growth rate and truncations to growth duration. PMID:18195356

  17. Sexual maturity in growing dinosaurs does not fit reptilian growth models.

    PubMed

    Lee, Andrew H; Werning, Sarah

    2008-01-15

    Recent histological studies suggest relatively rapid growth in dinosaurs. However, the timing of reproductive maturity (RM) in dinosaurs is poorly known because unambiguous indicators of RM are rare. One exception is medullary bone (MB), which is an ephemeral bony tissue that forms before ovulation in the marrow cavities of birds as a calcium source for eggshelling. Recently, MB also was described in a single specimen of the saurischian dinosaur Tyrannosaurus rex. Here, we report two other occurrences of MB: in another saurischian dinosaur, Allosaurus, and in the ornithischian dinosaur Tenontosaurus. We show by counting lines of arrested growth and performing growth curve reconstructions that Tenontosaurus, Allosaurus, and Tyrannosaurus were reproductively mature by 8, 10, and 18 years, respectively. RM in these dinosaurs coincided with a transition from growth acceleration to deceleration. It also far precedes predictions based on the growth rates of living reptiles scaled to similar size. Despite relatively rapid growth, dinosaurs were similar to reptiles in that RM developed before reaching asymptotic size. However, this reproductive strategy also occurs in medium- to large-sized mammals and correlates with a strategy of prolonged multiyear growth. RM in actively growing individuals suggests that these dinosaurs were born relatively precocial and experienced high adult mortality. The origin of the modern avian reproductive strategy in ornithuran birds likely coincided with their extreme elevations in growth rate and truncations to growth duration.

  18. Ki-67 staining for determination of rhesus macaque T cell proliferative responses ex vivo1

    PubMed Central

    Shedlock, Devon J.; Talbott, Kendra T.; Morrow, Matthew P.; Ferraro, Bernadette; Hokey, David A.; Muthumani, Karuppiah; Weiner, David B.

    2010-01-01

    The capacity for robust proliferation upon re-infection is a hallmark of adaptive immunity and the basis of vaccination. A widely used animal model for the study of human disease is the rhesus macaque (RM), where capacity for proliferation can be assessed ex vivo using carboxyfluorescein succinimidyl ester (CFSE)-based dilution assays. However, we show over the course of the standard ex vivo proliferation assay that CFSE-labeling at commonly-used dye concentrations induces significant cell death, but that this phenomenon is dose-dependent. Here we describe an alternative, semi-quantitative method for estimating T cell proliferative responses that avoids the putative biases associated with chemical modification. RM peripheral blood mononuclear cells were stimulated ex vivo with cognate peptides for five days, immunostained for intracellular Ki-67, and then analyzed by flow cytometry. We describe a gating strategy using Ki-67 and side light scatter, also a marker of blastogenesis, which correlates strongly with data from CFSE dilution. We show that this method is a valid tool for measuring RM antigen-specific cellular proliferation ex vivo and can be used as an alternative to CFSE dilution assays. PMID:20104580

  19. Modulatory effects of vitamin D on peripheral cellular immunity in patients with recurrent miscarriage.

    PubMed

    Chen, Xian; Yin, Biao; Lian, Ruo-Chun; Zhang, Tao; Zhang, Hong-Zhan; Diao, Liang-Hui; Li, Yu-Ye; Huang, Chun-Yu; Liang, De-Sheng; Zeng, Yong

    2016-12-01

    We aimed to investigate the modulatory effects of vitamin D on peripheral blood cellular immune response in patients with recurrent miscarriage (RM). The effect of vitamin D on the number of peripheral blood cells, T helper 1 (Th1) cytokines, and NK cytotoxicity was measured in 99 women with RM. The percentage of CD19 + B cells and NK cytotoxicity at an effector-to-target cell (E:T) ratio of 50:1, 25:1, and 12.5:1 were significantly higher in the vitamin D insufficiency group (VDI) than in the vitamin D normal group (VDN) (P<.05 each). The proportion of TNF-α-expressing Th cells was significantly higher in the vitamin D deficiency group (VDD) than in VDN (P<.05). However, there were no significant differences between VDI and VDD. This dysregulation was significantly reduced with 1,25(OH) 2 D supplementation. The data suggest that the abnormalities of cellular immune response were observed in RM patients with a low vitamin D level, which could be regulated to some extent with 1,25(OH) 2 D supplementation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Faraday rotation from magnesium II absorbers toward polarized background radio sources

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

    Farnes, J. S.; O'Sullivan, S. P.; Corrigan, M. E.

    2014-11-01

    Strong singly ionized magnesium (Mg II) absorption lines in quasar spectra typically serve as a proxy for intervening galaxies along the line of sight. Previous studies have found a correlation between the number of these Mg II absorbers and the Faraday rotation measure (RM) at ≈5 GHz. We cross-match a sample of 35,752 optically identified non-intrinsic Mg II absorption systems with 25,649 polarized background radio sources for which we have measurements of both the spectral index and RM at 1.4 GHz. We use the spectral index to split the resulting sample of 599 sources into flat-spectrum and steep-spectrum subsamples. Wemore » find that our flat-spectrum sample shows significant (∼3.5σ) evidence for a correlation between Mg II absorption and RM at 1.4 GHz, while our steep-spectrum sample shows no such correlation. We argue that such an effect cannot be explained by either luminosity or other observational effects, by evolution in another confounding variable, by wavelength-dependent polarization structure in an active galactic nucleus, by the Galactic foreground, by cosmological expansion, or by partial coverage models. We conclude that our data are most consistent with intervenors directly contributing to the Faraday rotation along the line of sight, and that the intervening systems must therefore have coherent magnetic fields of substantial strength ( B-bar =1.8±0.4 μG). Nevertheless, the weak nature of the correlation will require future high-resolution and broadband radio observations in order to place it on a much firmer statistical footing.« less

  1. Selfish restriction modification genes: resistance of a resident R/M plasmid to displacement by an incompatible plasmid mediated by host killing.

    PubMed

    Naito, Y; Naito, T; Kobayashi, I

    1998-01-01

    Previous work from this laboratory demonstrated that plasmids carrying a type II restriction-modification gene complex are not easily lost from their bacterial host because plasmid-free segregant cells are killed through chromosome cleavage. Here, we have followed the course of events that takes place when an Escherichia coli rec BC sbcA strain carrying a plasmid coding for the PaeR7I restriction-modification (R/M) gene complex is transformed by a plasmid with an identical origin of replication. The number of transformants that appeared was far fewer than with the restriction-minus (r-) control. Most of the transformants were very small. After prolonged incubation, the number and the size of the colonies increased, but this increase never attained the level of the r- control. Most of the transformed colonies retained the drug-resistance of the resident, r+ m+ plasmid. These results indicate that post-segregational host killing occurs when a plasmid bearing an R/M gene complex is displaced by an incompatible plasmid. Such cell killing eliminates the competitor plasmid along with the host and, thus, would allow persistence of the R/M plasmid in the neighboring, clonal host cells in nature. This phenomenon is reminiscent of mammalian apoptosis and other forms of altruistic cell death strategy against infection. This type of resistance to displacement was also studied in a wild type Escherichia coli strain that was normal for homologous recombination (rec+). A number of differences between the recBC sbcA strain and the rec+ strain were observed and these will be discussed.

  2. A polarized fast radio burst at low Galactic latitude

    NASA Astrophysics Data System (ADS)

    Petroff, E.; Burke-Spolaor, S.; Keane, E. F.; McLaughlin, M. A.; Miller, R.; Andreoni, I.; Bailes, M.; Barr, E. D.; Bernard, S. R.; Bhandari, S.; Bhat, N. D. R.; Burgay, M.; Caleb, M.; Champion, D.; Chandra, P.; Cooke, J.; Dhillon, V. S.; Farnes, J. S.; Hardy, L. K.; Jaroenjittichai, P.; Johnston, S.; Kasliwal, M.; Kramer, M.; Littlefair, S. P.; Macquart, J. P.; Mickaliger, M.; Possenti, A.; Pritchard, T.; Ravi, V.; Rest, A.; Rowlinson, A.; Sawangwit, U.; Stappers, B.; Sullivan, M.; Tiburzi, C.; van Straten, W.; ANTARES Collaboration; Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Ardid, M.; Aubert, J.-J.; Avgitas, T.; Baret, B.; Barrios-Martí, J.; Basa, S.; Bertin, V.; Biagi, S.; Bormuth, R.; Bourret, S.; Bouwhuis, M. C.; Bruijn, R.; Brunner, J.; Busto, J.; Capone, A.; Caramete, L.; Carr, J.; Celli, S.; Chiarusi, T.; Circella, M.; Coelho, J. A. B.; Coleiro, A.; Coniglione, R.; Costantini, H.; Coyle, P.; Creusot, A.; Deschamps, A.; de Bonis, G.; Distefano, C.; di Palma, I.; Donzaud, C.; Dornic, D.; Drouhin, D.; Eberl, T.; El Bojaddaini, I.; Elsässer, D.; Enzenhöfer, A.; Felis, I.; Fusco, L. A.; Galatà, S.; Gay, P.; Geißelsöder, S.; Geyer, K.; Giordano, V.; Gleixner, A.; Glotin, H.; Grégoire, T.; Gracia-Ruiz, R.; Graf, K.; Hallmann, S.; van Haren, H.; Heijboer, A. J.; Hello, Y.; Hernández-Rey, J. J.; Hößl, J.; Hofestädt, J.; Hugon, C.; Illuminati, G.; James, C. W.; de Jong, M.; Jongen, M.; Kadler, M.; Kalekin, O.; Katz, U.; Kießling, D.; Kouchner, A.; Kreter, M.; Kreykenbohm, I.; Kulikovskiy, V.; Lachaud, C.; Lahmann, R.; Lefèvre, D.; Leonora, E.; Lotze, M.; Loucatos, S.; Marcelin, M.; Margiotta, A.; Marinelli, A.; Martínez-Mora, J. A.; Mathieu, A.; Mele, R.; Melis, K.; Michael, T.; Migliozzi, P.; Moussa, A.; Mueller, C.; Nezri, E.; Pǎvǎlaş, G. E.; Pellegrino, C.; Perrina, C.; Piattelli, P.; Popa, V.; Pradier, T.; Quinn, L.; Racca, C.; Riccobene, G.; Roensch, K.; Sánchez-Losa, A.; Saldaña, M.; Salvadori, I.; Samtleben, D. F. E.; Sanguineti, M.; Sapienza, P.; Schnabel, J.; Seitz, T.; Sieger, C.; Spurio, M.; Stolarczyk, Th.; Taiuti, M.; Tayalati, Y.; Trovato, A.; Tselengidou, M.; Turpin, D.; Tönnis, C.; Vallage, B.; Vallée, C.; van Elewyck, V.; Vivolo, D.; Vizzoca, A.; Wagner, S.; Wilms, J.; Zornoza, J. D.; Zúñiga, J.; H.E.S.S. Collaboration; Abdalla, H.; Abramowski, A.; Aharonian, F.; Ait Benkhali, F.; Akhperjanian, A. G.; Andersson, T.; Angüner, E. O.; Arrieta, M.; Aubert, P.; Backes, M.; Balzer, A.; Barnard, M.; Becherini, Y.; Tjus, J. Becker; Berge, D.; Bernhard, S.; Bernlöhr, K.; Blackwell, R.; Böttcher, M.; Boisson, C.; Bolmont, J.; Bordas, P.; Bregeon, J.; Brun, F.; Brun, P.; Bryan, M.; Bulik, T.; Capasso, M.; Casanova, S.; Cerruti, M.; Chakraborty, N.; Chalme-Calvet, R.; Chaves, R. C. G.; Chen, A.; Chevalier, J.; Chrétien, M.; Colafrancesco, S.; Cologna, G.; Condon, B.; Conrad, J.; Cui, Y.; Davids, I. D.; Decock, J.; Degrange, B.; Deil, C.; Devin, J.; Dewilt, P.; Dirson, L.; Djannati-Ataï, A.; Domainko, W.; Donath, A.; Drury, L. O'c.; Dubus, G.; Dutson, K.; Dyks, J.; Edwards, T.; Egberts, K.; Eger, P.; Ernenwein, J.-P.; Eschbach, S.; Farnier, C.; Fegan, S.; Fernandes, M. V.; Fiasson, A.; Fontaine, G.; Förster, A.; Funk, S.; Füßling, M.; Gabici, S.; Gajdus, M.; Gallant, Y. A.; Garrigoux, T.; Giavitto, G.; Giebels, B.; Glicenstein, J. F.; Gottschall, D.; Goyal, A.; Grondin, M.-H.; Hadasch, D.; Hahn, J.; Haupt, M.; Hawkes, J.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hervet, O.; Hinton, J. A.; Hofmann, W.; Hoischen, C.; Holler, M.; Horns, D.; Ivascenko, A.; Jacholkowska, A.; Jamrozy, M.; Janiak, M.; Jankowsky, D.; Jankowsky, F.; Jingo, M.; Jogler, T.; Jouvin, L.; Jung-Richardt, I.; Kastendieck, M. A.; Katarzyński, K.; Kerszberg, D.; Khélifi, B.; Kieffer, M.; King, J.; Klepser, S.; Klochkov, D.; Kluźniak, W.; Kolitzus, D.; Komin, Nu.; Kosack, K.; Krakau, S.; Kraus, M.; Krayzel, F.; Krüger, P. P.; Laffon, H.; Lamanna, G.; Lau, J.; Lees, J.-P.; Lefaucheur, J.; Lefranc, V.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Leser, E.; Lohse, T.; Lorentz, M.; Liu, R.; López-Coto, R.; Lypova, I.; Marandon, V.; Marcowith, A.; Mariaud, C.; Marx, R.; Maurin, G.; Maxted, N.; Mayer, M.; Meintjes, P. J.; Meyer, M.; Mitchell, A. M. W.; Moderski, R.; Mohamed, M.; Mohrmann, L.; Morâ, K.; Moulin, E.; Murach, T.; de Naurois, M.; Niederwanger, F.; Niemiec, J.; Oakes, L.; O'Brien, P.; Odaka, H.; Öttl, S.; Ohm, S.; Ostrowski, M.; Oya, I.; Padovani, M.; Panter, M.; Parsons, R. D.; Pekeur, N. W.; Pelletier, G.; Perennes, C.; Petrucci, P.-O.; Peyaud, B.; Piel, Q.; Pita, S.; Poon, H.; Prokhorov, D.; Prokoph, H.; Pühlhofer, G.; Punch, M.; Quirrenbach, A.; Raab, S.; Reimer, A.; Reimer, O.; Renaud, M.; Reyes, R. De Los; Rieger, F.; Romoli, C.; Rosier-Lees, S.; Rowell, G.; Rudak, B.; Rulten, C. B.; Sahakian, V.; Salek, D.; Sanchez, D. A.; Santangelo, A.; Sasaki, M.; Schlickeiser, R.; Schulz, A.; Schüssler, F.; Schwanke, U.; Schwemmer, S.; Settimo, M.; Seyffert, A. S.; Shafi, N.; Shilon, I.; Simoni, R.; Sol, H.; Spanier, F.; Spengler, G.; Spies, F.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Stinzing, F.; Stycz, K.; Sushch, I.; Tavernet, J.-P.; Tavernier, T.; Taylor, A. M.; Terrier, R.; Tibaldo, L.; Tiziani, D.; Tluczykont, M.; Trichard, C.; Tuffs, R.; Uchiyama, Y.; Walt, D. J. Van Der; van Eldik, C.; van Rensburg, C.; van Soelen, B.; Vasileiadis, G.; Veh, J.; Venter, C.; Viana, A.; Vincent, P.; Vink, J.; Voisin, F.; Völk, H. J.; Vuillaume, T.; Wadiasingh, Z.; Wagner, S. J.; Wagner, P.; Wagner, R. M.; White, R.; Wierzcholska, A.; Willmann, P.; Wörnlein, A.; Wouters, D.; Yang, R.; Zabalza, V.; Zaborov, D.; Zacharias, M.; Zanin, R.; Zdziarski, A. A.; Zech, A.; Zefi, F.; Ziegler, A.; Żywucka, N.

    2017-08-01

    We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 ± 0.8 pc cm-3, a pulse duration of 2.8^{+1.2}_{-0.5} ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7^{+0.2}_{-0.1} Jy. The FRB originated at a Galactic longitude and latitude of 24.66°, 5.28° and 25° away from the Galactic Center. The burst was found to be 43 ± 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m-2 (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, γ-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.

  3. Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

    PubMed

    Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Kakeda, M; Yoneya, T; Tsumura, H; Ohashi, H; Yamaguchi, Y; Motoki, K; Sudo, T; Mori, K J

    1996-09-01

    The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM is based upon the synergistic effects of mSCF and mG-CSF.

  4. Rhodamine-based fluorescent probe for direct bio-imaging of lysosomal pH changes.

    PubMed

    Shi, Xue-Lin; Mao, Guo-Jiang; Zhang, Xiao-Bing; Liu, Hong-Wen; Gong, Yi-Jun; Wu, Yong-Xiang; Zhou, Li-Yi; Zhang, Jing; Tan, Weihong

    2014-12-01

    Intracellular pH plays a pivotal role in various biological processes. In eukaryotic cells, lysosomes contain numerous enzymes and proteins exhibiting a variety of activities and functions at acidic pH (4.5-5.5), and abnormal variation in the lysosomal pH causes defects in lysosomal function. Thus, it is important to investigate lysosomal pH in living cells to understand its physiological and pathological processes. In this work, we designed a one-step synthesized rhodamine derivative (RM) with morpholine as a lysosomes tracker, to detect lysosomal pH changes with high sensitivity, high selectivity, high photostability and low cytotoxicity. The probe RM shows a 140-fold fluorescence enhancement over a pH range from 7.4 to 4.5 with a pKa value of 5.23. Importantly, RM can detect the chloroquine-induced lysosomal pH increase and monitor the dexamethasone-induced lysosomal pH changes during apoptosis in live cells. All these features demonstrate its value of practical application in biological systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Accelerating Innovation in the Creation of Biovalue: The Cell and Gene Therapy Catapult.

    PubMed

    Gardner, John; Webster, Andrew

    2017-09-01

    The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to "accelerate" innovation. This article examines in detail one such agency, the United Kingdom's Cell and Gene Therapy Catapult (CGTC). We describe CGTC's role as an accelerator agency and its value narrative, which combines both "health and wealth." Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field.

  6. Lasp1 gene disruption is linked to enhanced cell migration and tumor formation Address for reprint requests and other correspondence: C. S. Chew, Inst. of Molecular Medicine and Genetics, Sanders R&E Bldg., Rm. CB 2803, Medical College of Georgia, Augusta, GA 30912-3175 (e-mail: cchew@mcg.edu).

    PubMed Central

    Zhang, Han; Chen, Xunsheng; Bollag, Wendy B.; Bollag, Roni J.; Sheehan, Daniel J.; Chew, Catherine S.

    2009-01-01

    Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1−/− mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1−/− mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1−/− MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models. PMID:19531578

  7. Oxidatively denatured proteins are degraded by an ATP-independent proteolytic pathway in Escherichia coli.

    PubMed

    Davies, K J; Lin, S W

    1988-01-01

    E. coli contains a soluble proteolytic pathway which can recognize and degrade oxidatively denatured proteins and protein fragments, and which may act as a "secondary antioxidant defense." We now provide evidence that this proteolytic pathway is distinct from the previously described ATP-dependent, and protease "La"-dependent, pathway which may degrade other abnormal proteins. Cells (K12) which were depleted of ATP, by arsenate treatment or anaerobic incubation (after growth on succinate), exhibited proteolytic responses to oxidative stress which were indistinguishable from those observed in cells with normal ATP levels. Furthermore, the proteolytic responses to oxidative damage by menadione or H2O2 were almost identical in the isogenic strains RM312 (a K12 derivative) and RM1385 (a lon deletion mutant of RM312). Since the lon (or capR) gene codes for the ATP-dependent protease "La," these results indicate that neither ATP nor protease "La" are required for the degradation of oxidatively denatured proteins. We next prepared cell-free extracts of K12, RM312, and RM1385 and tested the activity of their soluble proteases against proteins (albumin, hemoglobin, superoxide dismutase, catalase) which had been oxidatively denatured (in vitro) by exposure to .OH, .OH + O2- (+O2), H2O2, or ascorbate plus iron. The breakdown of oxidatively denatured proteins was several-fold higher than that of untreated proteins in extracts from all three strains, and ATP did not stimulate degradation. Incubation of extracts at 45 degrees C, which inactivates protease "La," actually stimulated the degradation of oxidatively denatured proteins. Although Ca2+ had little effect on proteolysis, serine reagents, transition metal chelators, and hemin effectively inhibited the degradation of oxidatively denatured proteins in both intact cells and cell-free extracts. Degradation of oxidatively denatured proteins in cell-free extracts was maximal at pH 7.8, and was unaffected by dialysis of the extracts against membranes with molecular weight cutoffs as high as 50,000. Our results indicate the presence of a neutral, ATP- and calcium- independent proteolytic pathway in the E. coli cytosol, which contains serine- and metallo- proteases (with molecular weights greater than 50,000), and which preferentially degrades oxidatively denatured proteins.

  8. Killer immunoglobulin-like receptors (KIRs) and HLA-C allorecognition patterns implicative of dominant activation of natural killer cells contribute to recurrent miscarriages.

    PubMed

    Faridi, R M; Agrawal, S

    2011-02-01

    Decidual natural killer (NK) cells play key developmental roles at the feto-maternal interface. Individual differences in NK-cell interactions are dependent on the combinations of variable killer immunoglobulin-like receptor (KIR) and HLA class-I gene products. As different receptor-ligand interactions may result in altered NK-cell-mediated immunity against pathogens, it is proposed that the relationship between these genes may be important in a state such as recurrent miscarriage (RM). We had earlier reported that the predisposition to RM is influenced by the maternal KIR gene content. In the present study, we have attempted to extend our findings in the light of contribution from the paternal antigens on the outcome of pregnancy, since maternal NK cells may potentially encounter non-self-paternal HLA-C alleles on trophoblasts. All HLA-C allotypes fall into two major KIR epitopes--C1 (HLA-C*01/*03/*07/*08/*12/*14/*16) and C2 (HLA-C*02/*04/*05/*06/*15/*17/*18)--on the basis of a dimorphism at position 80 of the α1 domain. PCR-sequence specific primer-based genotyping was used to determine the maternal KIR gene content and HLA-C genotypes down to allele level in couples experiencing RM and controls. KIR2DL1 with both partners homozygous for HLA C2 was significantly higher in control couples when compared with the patients [P = 0.0004, odds ratio (OR) = 0.28, 95% confidence interval (CI) = 0.13-0.58]. The activating KIR2DS2 with both partners homozygous for HLA C1 was significantly higher in patients when compared with the controls (P = 0.002, OR = 2.83, 95% CI = 1.47-5.40). Our results represented the 'top-end' of the activation spectrum of KIR-HLA-C compound genotype for NK cells and this may contribute to the immunological etiology of RM.

  9. Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: [64Cu]-DOTHA2-PEG-RM26.

    PubMed

    Mansour, Nematallah; Paquette, Michel; Ait-Mohand, Samia; Dumulon-Perreault, Véronique; Guérin, Brigitte

    2018-01-01

    Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA 2 ). Here we investigated the potential of a novel DOTHA 2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe 6 -Sta 13 -Leu 14 -NH 2 ]bombesin(6-14) (DOTHA 2 -PEG-RM26) to visualize prostate tumors by PET imaging. DOTHA 2 -PEG-RM26 was conveniently and efficiently assembled on solid support. The compound was radiolabeled with 64 Cu and its affinity, stability, cellular uptake on PC3 prostate cancer cells were evaluated. The in vitro and in vivo behavior of [ 64 Cu]DOTHA 2 -PEG-RM26 was examined by PET imaging using human PC3 prostate cancer xenografts and its behavior was compared to that of the analogous [ 64 Cu]NOTA-PEG-RM26. The inhibition constant of nat Cu-DOTHA 2 -PEG-RM26 was in the low nanomolar range (0.68±0.19 nM). The [ 64 Cu]DOTHA 2 -PEG-RM26 conjugate was prepared with a labeling yield >95% and molar activity of 56±3 GBq/μmol after a 5-min room temperature labeling. [ 64 Cu]-DOTHA 2 -PEG-RM26 demonstrated rapid blood and renal clearance as well as a high tumor uptake. Small animal PET images confirmed high and specific uptake in PC3 tumor. Both [ 64 Cu]-DOTHA 2 -PEG-RM26 and [ 64 Cu]-NOTA-PEG-RM26 displayed similar tumor and normal tissue uptakes at early time point post injection. [ 64 Cu]-DOTHA 2 -PEG-RM26 allows visualization of prostate tumors by PET imaging. DOTHA 2 enables fast 64 Cu chelation under mild condition, and as such could be used advantageously for the development of other 64 Cu-labeled peptide-derived PET tracers. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage.

    PubMed

    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-07-01

    Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

  11. Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors.

    PubMed

    Riddick, Nadeene E; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M; Plishka, Ronald J; Buckler-White, Alicia; Brenchley, Jason M; Hirsch, Vanessa M

    2015-12-09

    African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4(+) T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4(+) T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4(+) T cells, the preferred target cells of SIV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors

    PubMed Central

    Riddick, Nadeene E.; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M.; Plishka, Ronald J.; Buckler-White, Alicia; Brenchley, Jason M.

    2015-01-01

    ABSTRACT African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4+ T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4+ T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. IMPORTANCE African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4+ T cells, the preferred target cells of SIV. PMID:26656714

  13. Sensitivity of Breast Tumors to Oncolytic Viruses

    DTIC Science & Technology

    2005-08-01

    reproductions will be in black and white. 14. ABSTRACT The goal of this project is to develop novel therapies for breast cancer based on the oncolytic...effect than breast cancer cells. However, in syngeneic breast cancer system in vivo, rM51R-M virus is only partially effective at killing breast tumors...aggressive tumors that are resistant to more conventional therapies. 15. SUBJECT TERMS Vesicular stomatitis virus, interleukin 12, breast cancer

  14. TAAR1 induces a disturbed GSK3β phosphorylation in recurrent miscarriages through the ODC

    PubMed Central

    Stavrou, Stavroula; Gratz, Michael; Tremmel, Eileen; Kuhn, Christina; Hofmann, Simone; Heidegger, Helene; Peryanova, Mina; Hermelink, Kerstin; Hutter, Stefan; Toth, Bettina; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

    2018-01-01

    Objectives Thyroid hormones play an important role in the maintenance of pregnancy. Their derivates, endogenous amines, act via binding to the trace amine-associated receptor (TAAR1). The aim of our study was to analyse the regulation of TAAR1, serine/threonine kinase (pGSK3β) and ornithine decarboxylase (ODC) in placentas of healthy pregnancies, spontaneous (SM) and recurrent miscarriages (RM) and to investigate the influence of thyroid hormone derivates on TAAR1 expression in trophoblast model cells in vitro. Methods Patients with SM (n = 15) and RM (n = 15) were compared with patients with healthy pregnancies (n = 15) (pregnancy weeks 7–13 each). Immunohistochemistry was applied to analyse placental TAAR1, pGSK3β and ODC expression. Protein expression of the receptors after stimulation with T3, T1AM and RO5203548 in BeWo trophoblast model cells was determined via Western blot. Double-immunofluorescence was used to determine placental expression of TAAR1 and ODC. Results Levels of TAAR1, pGSK3β and ODC were higher in placentas of RM in comparison to healthy controls. Stimulation of BeWo cells with T3, T1AM and RO5203548 significantly increased TAAR1 expression. ODC expression in BeWo cells was upregulated through T3. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected. Conclusions Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T3 substitution plays for patients. PMID:29472377

  15. Clinical comparison between the retromandibular approach for reduction and fixation and endoscope-assisted open reduction and internal fixation for mandibular condyle fractures.

    PubMed

    Nogami, Shinnosuke; Takahashi, Tetsu; Yamauchi, Kensuke; Miyamoto, Ikuya; Kaneuji, Takeshi; Yamamoto, Noriaki; Yoshiga, Daigo; Yamashita, Yoshihiro

    2012-11-01

    Endoscope-assisted transoral open reduction and internal fixation (EAORIF) for mandibular condyle fractures has recently become popular because it is minimally invasive, provides excellent visibility without a large incision, and reduces surgical scarring and the risk of facial nerve injury. This report describes a retrospective clinical study that compared certain clinical parameters, including postoperative function, between the retromandibular (RM) approach and EAORIF. Fifteen patients were treated by the RM approach, whereas 15 underwent EAORIF between July 2006 and September 2011 at Kyushu Dental College, Japan. Clinical indices comprised fracture line, fracture type, number of plates used, surgical duration, bleeding amount, and functional items, including maximum interincisal opening, mandibular deviation on the opening pathway, malocclusion, facial paresthesia, and temporomandibular joint pain and clicking. The areas subjected to either approach included lower neck and subcondyle. The RM approach was used for mandibular condyle fractures with dislocation of a small bone segment. Both groups used 2 plates in all cases. Surgical duration, maximum interincisal opening, mandibular deviation, occlusion, and temporomandibular joint function at 6 months after surgery were comparable between groups. The average bleeding amount in the EAORIF group was greater than in the RM group. One patient from the RM group developed facial paresthesia that persisted for 6 months after surgery. It was concluded that surgical treatment was suitable for fractures of the lower neck and subcondylar. Both procedures showed good results in the functional items of this study.

  16. A diagnostic algorithm to optimize data collection and interpretation of Ripple Maps in atrial tachycardias.

    PubMed

    Koa-Wing, Michael; Nakagawa, Hiroshi; Luther, Vishal; Jamil-Copley, Shahnaz; Linton, Nick; Sandler, Belinda; Qureshi, Norman; Peters, Nicholas S; Davies, D Wyn; Francis, Darrel P; Jackman, Warren; Kanagaratnam, Prapa

    2015-11-15

    Ripple Mapping (RM) is designed to overcome the limitations of existing isochronal 3D mapping systems by representing the intracardiac electrogram as a dynamic bar on a surface bipolar voltage map that changes in height according to the electrogram voltage-time relationship, relative to a fiduciary point. We tested the hypothesis that standard approaches to atrial tachycardia CARTO™ activation maps were inadequate for RM creation and interpretation. From the results, we aimed to develop an algorithm to optimize RMs for future prospective testing on a clinical RM platform. CARTO-XP™ activation maps from atrial tachycardia ablations were reviewed by two blinded assessors on an off-line RM workstation. Ripple Maps were graded according to a diagnostic confidence scale (Grade I - high confidence with clear pattern of activation through to Grade IV - non-diagnostic). The RM-based diagnoses were corroborated against the clinical diagnoses. 43 RMs from 14 patients were classified as Grade I (5 [11.5%]); Grade II (17 [39.5%]); Grade III (9 [21%]) and Grade IV (12 [28%]). Causes of low gradings/errors included the following: insufficient chamber point density; window-of-interest<100% of cycle length (CL); <95% tachycardia CL mapped; variability of CL and/or unstable fiducial reference marker; and suboptimal bar height and scar settings. A data collection and map interpretation algorithm has been developed to optimize Ripple Maps in atrial tachycardias. This algorithm requires prospective testing on a real-time clinical platform. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis.

    PubMed

    Perdomo, Carolina; Zedler, Ulrike; Kühl, Anja A; Lozza, Laura; Saikali, Philippe; Sander, Leif E; Vogelzang, Alexis; Kaufmann, Stefan H E; Kupz, Andreas

    2016-11-22

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (T RM ) cells have been implicated in protective immune responses against viral infections, but the role of T RM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and T RM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4 + T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8 + T cells displayed prototypical T RM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development. Copyright © 2016 Perdomo et al.

  18. Cell-derived microparticles and vascular pregnancy complications: a systematic and comprehensive review.

    PubMed

    Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Llurba, Elisa; Vilardell-Tarres, Miquel

    2013-02-01

    To assess current studies on the relationship between cell-derived microparticles (cMP) and recurrent miscarriages (RM) and pre-eclampsia (PE), and review the relationships between cMP and inflammatory and clot pathways, antiphospholipid antibodies (aPL), cytokines, and pregnancy complications. Systematic and comprehensive review of the literature from January 2000 to January 2012. Vall d'Hebron University Hospital. Women with recurrent miscarriages or PE, healthy nonpregnant women, and healthy pregnant women. None. Comparison of cMP numbers and types among groups. Platelet and endothelial cMP are increased in women with normal pregnancies compared with nonpregnant healthy women. Only five case-control studies regarding cMP and RM and 16 on cMP and PE were found to match our objective. Three of five articles referring to RM showed differences in cMP numbering, and 13 of 16 on cMP and PE showed differences in some type of cMP compared with controls. Cell-derived microparticles were raised in normal pregnancy. Recurrent miscarriage seems to be related to endothelial and platelet cell activation and/or consumption. An increase in almost all cMP types was observed in PE. A relationship between cMP and endothelial activation and proinflammatory status seems to exist. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Large Magneto-ionic Variations toward the Galactic Center Magnetar, PSR J1745-2900

    NASA Astrophysics Data System (ADS)

    Desvignes, G.; Eatough, R. P.; Pen, U. L.; Lee, K. J.; Mao, S. A.; Karuppusamy, R.; Schnitzeler, D. H. F. M.; Falcke, H.; Kramer, M.; Wucknitz, O.; Spitler, L. G.; Torne, P.; Liu, K.; Bower, G. C.; Cognard, I.; Lyne, A. G.; Stappers, B. W.

    2018-01-01

    Polarized radio emission from PSR J1745‑2900 has already been used to investigate the strength of the magnetic field in the Galactic center (GC), close to Sagittarius A*. Here we report how persistent radio emission from this magnetar, for over four years since its discovery, has revealed large changes in the observed Faraday rotation measure (RM), by up to 3500 rad m‑2 (a 5% fractional change). From simultaneous analysis of the dispersion measure, we determine that these fluctuations are dominated by variations in either the projected magnetic field or the free electron content within the GC, along the changing line of sight to the rapidly moving magnetar. From a structure function analysis of RM variations, and a recent epoch of rapid change of RM, we determine a minimum scale of magneto-ionic fluctuations of size ∼2 au at the GC distance, inferring PSR J1745‑2900 is just ∼0.1 pc behind an additional scattering screen.

  20. A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research and Regenerative Medicine Between the Public and the Scientific Community

    PubMed Central

    Inoue, Yusuke; Ikka, Tsunakuni; Kishimoto, Atsuo

    2018-01-01

    Abstract Owing to the rapid progress in stem cell research (SCR) and regenerative medicine (RM), society's expectation and interest in these fields are increasing. For effective communication on issues concerning SCR and RM, surveys for understanding the interests of stakeholders is essential. For this purpose, we conducted a large‐scale survey with 2,160 public responses and 1,115 responses from the member of the Japanese Society for Regenerative Medicine. Results showed that the public is more interested in the post‐realization aspects of RM, such as cost of care, countermeasures for risks and accidents, and clarification of responsibility and liability, than in the scientific aspects; the latter is of greater interest only to scientists. Our data indicate that an increased awareness about RM‐associated social responsibility and regulatory framework is required among scientists, such as those regarding its benefits, potential accidents, abuse, and other social consequences. Awareness regarding the importance of communication and education for scientists are critical to bridge the gaps in the interests of the public and scientists. Stem Cells Translational Medicine 2018;7:251–257 PMID:29372590

  1. Apoptotic induction of skin cancer cell death by plant extracts.

    PubMed

    Thuncharoen, Walairat; Chulasiri, Malin; Nilwarangkoon, Sirinun; Nakamura, Yukio; Watanapokasin, Ramida

    2013-01-01

    The aim of the present study was to investigate the effects of plant extracts on cancer apoptotic induction. Human epidermoid carcinoma A431 cell line, obtained from the American Type Culture Collection (ATCC, Manassas, VA), was maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37 degrees C, 5% carbon dioxide (CO2). Plant extract solutions were obtained from S & J international enterprises public company limited. These plant extracts include 50% hydroglycol extracts from Etlingera elatior (Jack) R.M.Smith (torch ginger; EE), Rosa damascene (damask rose; DR) and Rafflesia kerrii Meijer (bua phut; RM). The cell viability, time and dose dependency were determined by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. A431 cells were treated with the plant extracts and stained with Hoechst 33342 fluorescent staining dye. Cell viability was demonstrated by the inhibitory concentration 50% (IC50). The anti-proliferative effects were shown to be dependent on time and dose. Typical characteristics of apoptosis which are cell morphological changes and chromatin condensation were clearly observed. The plant extracts was shown to be effective for anti-proliferation and induction of apoptosis cell death in skin cancer cells. Therefore, mechanisms underlying the cell death and its potential use for treatment of skin cancer will be further studied.

  2. Dynamics of Photoexcitation and Photocatalysis at Nanostructured Carbon Interfaces

    DTIC Science & Technology

    2015-07-14

    nanotubes with a sacrificial polymer and eliminating the polymer using a critical point drying process. This process creates aerogel structures that...Bindl DJ, Jacobberger RM, Wu M-Y, Singha Roy S, Arnold MS, Semiconducting Carbon Nanotube Aerogel Bulk Heterojunction Solar Cells, Small 10 (16), pp...ACS Nano 2015, 9 (1), 564-572. Ye Y, Bindl DJ, Jacobberger RM, Wu M-Y, Singha Roy S, Arnold MS, Semiconducting Carbon Nanotube Aerogel Bulk

  3. Sensitivity of Breast Tumors to Oncolytic Viruses

    DTIC Science & Technology

    2006-08-01

    therapies for breast cancer based on the oncolytic virus, vesicular stomatitis virus (VSV). Studies have shown that matrix (M) protein mutants of VSV, such...more resistant to VSV-induced cytopathic effect than breast cancer cells. However, in syngeneic breast cancer system in vivo, rM51R-M virus is only...interleukin 12, breast cancer , interferon 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  4. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

    PubMed Central

    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-01-01

    Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

  5. Red Marrow-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with 177Lu-Lilotomab Satetraxetan, a Novel Anti-CD37 Antibody-Radionuclide Conjugate.

    PubMed

    Blakkisrud, Johan; Løndalen, Ayca; Dahle, Jostein; Turner, Simon; Holte, Harald; Kolstad, Arne; Stokke, Caroline

    2017-01-01

    Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. 177 Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity. Eight patients with relapsed CD37+ indolent B-cell non-Hodgkin lymphoma were included for RM dosimetry. Hybrid SPECT and CT images were used to estimate the activity concentration in the RM of L2-L4. Pharmacokinetic parameters were calculated after measurement of the 177 Lu-lilotomab satetraxetan concentration in blood samples. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The mean absorbed doses to RM were 0.9 mGy/MBq for arm 1 (lilotomab+) and 1.5 mGy/MBq for arm 2 (lilotomab-). There was a statistically significant difference between arms 1 and 2 (Student t test, P = 0.02). Total RM-absorbed doses ranged from 67 to 127 cGy in arm 1 and from 158 to 207 cGy in arm 2. For blood, the area under the curve was higher with lilotomab predosing than without (P = 0.001), whereas the volume of distribution and the clearance of 177 Lu-lilotomab satetraxetan was significantly lower (P = 0.01 and P = 0.03, respectively). Patients with grade 3/4 thrombocytopenia had received significantly higher radiation doses to RM than patients with grade 1/2 thrombocytopenia (P = 0.02). A surrogate, non-imaging-based, method underestimated the RM dose and did not show any correlation with toxicity. Predosing with lilotomab reduces the RM-absorbed dose for 177 Lu-lilotomab satetraxetan patients. The decrease in RM dose could be explained by the lower volume of distribution. Hematologic toxicity was more severe for patients receiving higher absorbed radiation doses, indicating that adverse events possibly can be predicted by the calculation of absorbed dose to RM from SPECT/CT images. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. A heterodimeric [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] αvβ3/GRPr-targeting antagonist radiotracer for PET imaging of prostate tumors.

    PubMed

    Durkan, Kubra; Jiang, Zongrun; Rold, Tammy L; Sieckman, Gary L; Hoffman, Timothy J; Bandari, Rajendra Prasad; Szczodroski, Ashley F; Liu, Liqin; Miao, Yubin; Reynolds, Tamila Stott; Smith, Charles J

    2014-02-01

    In the present study, we describe a (64)Cu-radiolabeled heterodimeric peptide conjugate for dual αvβ3/GRPr (αvβ3 integrin/gastrin releasing peptide receptor) targeting of the form [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] (RGD: the amino acid sequence [Arg-Gly-Asp], a nonregulatory peptide used for αvβ3 integrin receptor targeting; Glu: glutamic acid; NO2A: 1,4,7-triazacyclononane-1,4-diacetic acid; 6-Ahx: 6-amino hexanoic acid; and RM2: (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2), an antagonist analogue of bombesin (BBN) peptide used for GRPr targeting). RGD-Glu-6Ahx-RM2] was conjugated to a NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) complexing agent to produce [RGD-Glu-[NO2A]-6-Ahx-RM2], which was purified by reversed-phase high-performance liquid chromatography (RP-HPLC) and characterized by electrospray ionization-mass spectrometry (ESI-MS). Radiolabeling of the conjugate with (64)Cu produced [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2 in high radiochemical yield (≥95%). In vivo behavior of the radiolabeled peptide conjugate was investigated in normal CF-1 mice and in the PC-3 human prostate cancer experimental model. A competitive displacement receptor binding assay in human prostate PC-3 cells using (125)I-[Tyr(4)]BBN as the radioligand showed high binding affinity of [RGD-Glu-[(nat)Cu-NO2A]-6-Ahx-RM2] conjugate for the GRPr (3.09±0.34 nM). A similar assay in human, glioblastoma U87-MG cells using (125)I-Echistatin as the radioligand indicated a moderate receptor-binding affinity for the αvβ3 integrin (518±37.5 nM). In vivo studies of [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] showed high accumulation (4.86±1.01 %ID/g, 1h post-intravenous injection (p.i.)) and prolonged retention (4.26±1.23 %ID/g, 24h p.i.) of tracer in PC-3 tumor-bearing mice. Micro-positron emission tomography (microPET) molecular imaging studies produced high-quality, high contrast images in PC-3 tumor-bearing mice at 4h p.i. The favorable pharmacokinetics and enhanced tumor uptake of (64)Cu-NOTA-RGD-Glu-6Ahx-RM2 warrant further investigations for dual integrin and GRPr-positive tumor imaging and possible radiotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. UV-luminous, star-forming hosts of z ~ 2 reddened quasars in the Dark Energy Survey

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

    Wethers, C. F.; Banerji, M.; Hewett, P. C.

    We present the first rest-frame UV population study of 17 heavily reddened, high-luminosity (E(B-V)more » $$_{\\rm{QSO}}\\gtrsim$$ 0.5; L$$_{\\rm{bol}}>$$ 10$$^{46}$$ergs$$^{-1}$$) broad-line quasars at $1.5 < z < 2.7$. We combine the first year of deep, optical, ground-based observations from the Dark Energy Survey (DES) with the near infrared VISTA Hemisphere Survey (VHS) and UKIDSS Large Area Survey (ULAS) data, from which the reddened quasars were initially identified. We demonstrate that the significant dust reddening towards the quasar in our sample allows host galaxy emission to be detected at the rest-frame UV wavelengths probed by the DES photometry. By exploiting this reddening effect, we disentangle the quasar emission from that of the host galaxy via spectral energy distribution (SED) fitting. We find evidence for a relatively unobscured, star-forming host galaxy in at least ten quasars, with a further three quasars exhibiting emission consistent with either star formation or scattered light. From the rest-frame UV emission, we derive instantaneous, dust-corrected star formation rates (SFRs) in the range 25 < SFR$$_{\\rm{UV}}$$ < 365 M$$_{\\odot}$$yr$$^{-1}$$, with an average SFR$$_{\\rm{UV}}$$ = 130 $$\\pm$$ 95 M$$_{\\odot}$$yr$$^{-1}$$. In conclusion, we find a broad correlation between SFR$$_{\\rm{UV}}$$ and the bolometric quasar luminosity. Overall, our results show evidence for coeval star formation and black hole accretion occurring in luminous, reddened quasars at the peak epoch of galaxy formation.« less

  8. UV-luminous, star-forming hosts of z ~ 2 reddened quasars in the Dark Energy Survey

    DOE PAGES

    Wethers, C. F.; Banerji, M.; Hewett, P. C.; ...

    2018-01-05

    We present the first rest-frame UV population study of 17 heavily reddened, high-luminosity (E(B-V)more » $$_{\\rm{QSO}}\\gtrsim$$ 0.5; L$$_{\\rm{bol}}>$$ 10$$^{46}$$ergs$$^{-1}$$) broad-line quasars at $1.5 < z < 2.7$. We combine the first year of deep, optical, ground-based observations from the Dark Energy Survey (DES) with the near infrared VISTA Hemisphere Survey (VHS) and UKIDSS Large Area Survey (ULAS) data, from which the reddened quasars were initially identified. We demonstrate that the significant dust reddening towards the quasar in our sample allows host galaxy emission to be detected at the rest-frame UV wavelengths probed by the DES photometry. By exploiting this reddening effect, we disentangle the quasar emission from that of the host galaxy via spectral energy distribution (SED) fitting. We find evidence for a relatively unobscured, star-forming host galaxy in at least ten quasars, with a further three quasars exhibiting emission consistent with either star formation or scattered light. From the rest-frame UV emission, we derive instantaneous, dust-corrected star formation rates (SFRs) in the range 25 < SFR$$_{\\rm{UV}}$$ < 365 M$$_{\\odot}$$yr$$^{-1}$$, with an average SFR$$_{\\rm{UV}}$$ = 130 $$\\pm$$ 95 M$$_{\\odot}$$yr$$^{-1}$$. In conclusion, we find a broad correlation between SFR$$_{\\rm{UV}}$$ and the bolometric quasar luminosity. Overall, our results show evidence for coeval star formation and black hole accretion occurring in luminous, reddened quasars at the peak epoch of galaxy formation.« less

  9. The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis.

    PubMed

    Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Singh, Amar; Lokensgard, James R

    2017-04-13

    Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bT RM ) following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8 + T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bT RMs . In wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8 + T cell populations from KLRG1 + CD127 - (SLEC) to KLRG1 - CD127 + (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8 + T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8 + T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8 + T cells was phenotyped as CD103 + CD69 + , markers of bT RM , and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103 + bT RM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs. Taken together, our results indicate that bT RMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.

  10. Ribbons characterize magnetohydrodynamic magnetic fields better than lines: a lesson from dynamo theory

    NASA Astrophysics Data System (ADS)

    Blackman, Eric G.; Hubbard, Alexander

    2014-08-01

    Blackman and Brandenburg argued that magnetic helicity conservation in dynamo theory can in principle be captured by diagrams of mean field dynamos when the magnetic fields are represented by ribbons or tubes, but not by lines. Here, we present such a schematic ribbon diagram for the α2 dynamo that tracks magnetic helicity and provides distinct scales of large-scale magnetic helicity, small-scale magnetic helicity, and kinetic helicity involved in the process. This also motivates our construction of a new `2.5 scale' minimalist generalization of the helicity-evolving equations for the α2 dynamo that separately allows for these three distinct length-scales while keeping only two dynamical equations. We solve these equations and, as in previous studies, find that the large-scale field first grows at a rate independent of the magnetic Reynolds number RM before quenching to an RM-dependent regime. But we also show that the larger the ratio of the wavenumber where the small-scale current helicity resides to that of the forcing scale, the earlier the non-linear dynamo quenching occurs, and the weaker the large-scale field is at the turnoff from linear growth. The harmony between the theory and the schematic diagram exemplifies a general lesson that magnetic fields in magnetohydrodynamic are better visualized as two-dimensional ribbons (or pairs of lines) rather than single lines.

  11. CACTA-superfamily transposable element is inserted in MYB transcription factor gene of soybean line producing variegated seeds.

    PubMed

    Yan, Fan; Di, Shaokang; Takahashi, Ryoji

    2015-08-01

    The R gene of soybean, presumably encoding a MYB transcription factor, controls seed coat color. The gene consists of multiple alleles, R (black), r-m (black spots and (or) concentric streaks on brown seed), and r (brown seed). This study was conducted to determine the structure of the MYB transcription factor gene in a near-isogenic line (NIL) having r-m allele. PCR amplification of a fragment of the candidate gene Glyma.09G235100 generated a fragment of about 1 kb in the soybean cultivar Clark, whereas a fragment of about 14 kb in addition to fragments of 1 and 1.4 kb were produced in L72-2040, a Clark 63 NIL with the r-m allele. Clark 63 is a NIL of Clark with the rxp and Rps1 alleles. A DNA fragment of 13 060 bp was inserted in the intron of Glyma.09G235100 in L72-2040. The fragment had the CACTA motif at both ends, imperfect terminal inverted repeats (TIR), inverse repetition of short sequence motifs close to the 5' and 3' ends, and a duplication of three nucleotides at the site of integration, indicating that it belongs to a CACTA-superfamily transposable element. We designated the element as Tgm11. Overall nucleotide sequence, motifs of TIR, and subterminal repeats were similar to those of Tgm1 and Tgs1, suggesting that these elements comprise a family.

  12. In Vitro and In Vivo Evaluation of a 18F-Labeled High Affinity NOTA Conjugated Bombesin Antagonist as a PET Ligand for GRPR-Targeted Tumor Imaging

    PubMed Central

    Velikyan, Irina; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Antoni, Gunnar; Sandström, Mattias; Tolmachev, Vladimir; Orlova, Anna

    2013-01-01

    Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethylene glycol (PEG2) spacer (NOTA-P2-RM26) labeled with 68Ga and 111In. We found that this conjugate has favorable properties for in vivo imaging of GRPR-expression. The focus of this study was to develop a 18F-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with 18F using aluminum-fluoride chelation. Stability, in vitro binding specificity and cellular processing tests were performed. The inhibition efficiency (IC50) of the [natF]AlF-NOTA-P2-RM26 was compared to that of the natGa-loaded peptide using 125I-Tyr4-BBN as the displacement radioligand. The pharmacokinetics and in vivo binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with 18F within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/µmol). The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [natF]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC50=4.4±0.8 nM). The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [18F]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p.i. was 5.5±0.7 %ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87±42, 159±47, 38±16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high in vivo stability of the Al-F bond. High contrast PET image was obtained 3 h p.i. The initial biological results suggest that [18F]AlF-NOTA-P2-RM26 is a promising candidate for PET imaging of GRPR in vivo. PMID:24312607

  13. Localization of a bacterial group II intron-encoded protein in human cells.

    PubMed

    Reinoso-Colacio, Mercedes; García-Rodríguez, Fernando Manuel; García-Cañadas, Marta; Amador-Cubero, Suyapa; García Pérez, José Luis; Toro, Nicolás

    2015-08-05

    Group II introns are mobile retroelements that self-splice from precursor RNAs to form ribonucleoparticles (RNP), which can invade new specific genomic DNA sites. This specificity can be reprogrammed, for insertion into any desired DNA site, making these introns useful tools for bacterial genetic engineering. However, previous studies have suggested that these elements may function inefficiently in eukaryotes. We investigated the subcellular distribution, in cultured human cells, of the protein encoded by the group II intron RmInt1 (IEP) and several mutants. We created fusions with yellow fluorescent protein (YFP) and with a FLAG epitope. We found that the IEP was localized in the nucleus and nucleolus of the cells. Remarkably, it also accumulated at the periphery of the nuclear matrix. We were also able to identify spliced lariat intron RNA, which co-immunoprecipitated with the IEP, suggesting that functional RmInt1 RNPs can be assembled in cultured human cells.

  14. Localization of a bacterial group II intron-encoded protein in human cells

    PubMed Central

    Reinoso-Colacio, Mercedes; García-Rodríguez, Fernando Manuel; García-Cañadas, Marta; Amador-Cubero, Suyapa; Pérez, José Luis García; Toro, Nicolás

    2015-01-01

    Group II introns are mobile retroelements that self-splice from precursor RNAs to form ribonucleoparticles (RNP), which can invade new specific genomic DNA sites. This specificity can be reprogrammed, for insertion into any desired DNA site, making these introns useful tools for bacterial genetic engineering. However, previous studies have suggested that these elements may function inefficiently in eukaryotes. We investigated the subcellular distribution, in cultured human cells, of the protein encoded by the group II intron RmInt1 (IEP) and several mutants. We created fusions with yellow fluorescent protein (YFP) and with a FLAG epitope. We found that the IEP was localized in the nucleus and nucleolus of the cells. Remarkably, it also accumulated at the periphery of the nuclear matrix. We were also able to identify spliced lariat intron RNA, which co-immunoprecipitated with the IEP, suggesting that functional RmInt1 RNPs can be assembled in cultured human cells. PMID:26244523

  15. Television's Dilemma: Information vs. Entertainment.

    ERIC Educational Resources Information Center

    Saltzman, Joe

    1984-01-01

    As long as people want to see entertainment programs that deal with real people and problems and as long as people tune into newscasts that feel they must entertain as well as inform, that thin line between news and entertainment will remain a twilight zone filled with superficiality and sensationalism. (RM)

  16. Ships Passing in the Night: Spectroscopic Analysis of Two Ultra-faint Satellites in the Constellation Carina

    DOE PAGES

    Li, T. S.; Simon, J. D.; Pace, A. B.; ...

    2018-04-25

    Here, we present Magellan/IMACS, Anglo-Australian Telescope/AAOmega+2dF, and Very Large Telescope/GIRAFFE+FLAMES spectroscopy of the Carina II (Car II) and Carina III (Car III) dwarf galaxy candidates, recently discovered in the Magellanic Satellites Survey (MagLiteS). We identify 18 member stars in Car II, including two binaries with variable radial velocities and two RR Lyrae stars. The other 14 members have a mean heliocentric velocitymore » $${v}_{\\mathrm{hel}}=477.2\\pm 1.2$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$ and a velocity dispersion of $${\\sigma }_{v}={3.4}_{-0.8}^{+1.2}$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$. Assuming Car II is in dynamical equilibrium, we derive a total mass within the half-light radius of $${1.0}_{-0.4}^{+0.8}\\times {10}^{6}$$ $${M}_{\\odot }$$, indicating a mass-to-light ratio of $${369}_{-161}^{+309}$$ $${M}_{\\odot }$$/$${L}_{\\odot }$$. From equivalent width measurements of the calcium triplet lines of nine red giant branch (RGB) stars, we derive a mean metallicity of $${\\rm{[Fe/H]}}=-2.44\\pm 0.09$$ with dispersion $${\\sigma }_{{\\rm{[Fe/H]}}}={0.22}_{-0.07}^{+0.10}$$. Considering both the kinematic and chemical properties, we conclude that Car II is a dark-matter-dominated dwarf galaxy. For Car III, we identify four member stars, from which we calculate a systemic velocity of $${v}_{\\mathrm{hel}}={284.6}_{-3.1}^{+3.4}$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$. The brightest RGB member of Car III has a metallicity of $${\\rm{[Fe/H]}}\\,=-1.97\\pm 0.12$$. Due to the small size of the Car III spectroscopic sample, we cannot conclusively determine its nature. Although these two systems have the smallest known physical separation ($${\\rm{\\Delta }}d\\sim 10\\,\\mathrm{kpc}$$) among Local Group satellites, the large difference in their systemic velocities, $$\\sim 200\\,\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$, indicates that they are unlikely to be a bound pair. One or both systems are likely associated with the Large Magellanic Cloud (LMC), and may remain LMC satellites today. No statistically significant excess of γ-ray emission is found at the locations of Car II and Car III in eight years of Fermi-LAT data.« less

  17. Ships Passing in the Night: Spectroscopic Analysis of Two Ultra-faint Satellites in the Constellation Carina

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

    Li, T. S.; Simon, J. D.; Pace, A. B.

    Here, we present Magellan/IMACS, Anglo-Australian Telescope/AAOmega+2dF, and Very Large Telescope/GIRAFFE+FLAMES spectroscopy of the Carina II (Car II) and Carina III (Car III) dwarf galaxy candidates, recently discovered in the Magellanic Satellites Survey (MagLiteS). We identify 18 member stars in Car II, including two binaries with variable radial velocities and two RR Lyrae stars. The other 14 members have a mean heliocentric velocitymore » $${v}_{\\mathrm{hel}}=477.2\\pm 1.2$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$ and a velocity dispersion of $${\\sigma }_{v}={3.4}_{-0.8}^{+1.2}$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$. Assuming Car II is in dynamical equilibrium, we derive a total mass within the half-light radius of $${1.0}_{-0.4}^{+0.8}\\times {10}^{6}$$ $${M}_{\\odot }$$, indicating a mass-to-light ratio of $${369}_{-161}^{+309}$$ $${M}_{\\odot }$$/$${L}_{\\odot }$$. From equivalent width measurements of the calcium triplet lines of nine red giant branch (RGB) stars, we derive a mean metallicity of $${\\rm{[Fe/H]}}=-2.44\\pm 0.09$$ with dispersion $${\\sigma }_{{\\rm{[Fe/H]}}}={0.22}_{-0.07}^{+0.10}$$. Considering both the kinematic and chemical properties, we conclude that Car II is a dark-matter-dominated dwarf galaxy. For Car III, we identify four member stars, from which we calculate a systemic velocity of $${v}_{\\mathrm{hel}}={284.6}_{-3.1}^{+3.4}$$ $$\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$. The brightest RGB member of Car III has a metallicity of $${\\rm{[Fe/H]}}\\,=-1.97\\pm 0.12$$. Due to the small size of the Car III spectroscopic sample, we cannot conclusively determine its nature. Although these two systems have the smallest known physical separation ($${\\rm{\\Delta }}d\\sim 10\\,\\mathrm{kpc}$$) among Local Group satellites, the large difference in their systemic velocities, $$\\sim 200\\,\\mathrm{km}\\,{{\\rm{s}}}^{-1}$$, indicates that they are unlikely to be a bound pair. One or both systems are likely associated with the Large Magellanic Cloud (LMC), and may remain LMC satellites today. No statistically significant excess of γ-ray emission is found at the locations of Car II and Car III in eight years of Fermi-LAT data.« less

  18. Accelerating Innovation in the Creation of Biovalue

    PubMed Central

    Webster, Andrew

    2017-01-01

    The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to “accelerate” innovation. This article examines in detail one such agency, the United Kingdom’s Cell and Gene Therapy Catapult (CGTC). We describe CGTC’s role as an accelerator agency and its value narrative, which combines both “health and wealth.” Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field. PMID:28845068

  19. A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

    PubMed

    Bossi, P; Miceli, R; Locati, L D; Ferrari, D; Vecchio, S; Moretti, G; Denaro, N; Caponigro, F; Airoldi, M; Moro, C; Vaccher, E; Sponghini, A; Caldara, A; Rinaldi, G; Ferrau, F; Nolè, F; Lo Vullo, S; Tettamanzi, F; Hollander, L; Licitra, L

    2017-11-01

    B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. EudraCT# 2011-002564-24. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Turbulent Flow Enhancement by Polyelectrolyte Additives: Mechanistic Implications for Drag Reduction.

    NASA Astrophysics Data System (ADS)

    Wagger, David Leonard

    1992-01-01

    The drag reduction phenomenon was experimentally studied in two pipes, of diameters 1.46 and 1.02 cm, using seven polyelectrolytic HPAM additives, with molecular weights from 1 to 20 times 10^6 g/mole and degree of backbone hydrolysis from 8 to 60%, at concentrations from 1 to 1000 wppm, in saline solutions containing from 0.3 to 0.00001 N NaCl. Both laminar and turbulent flow behavior were greatly influenced by salinity-induced changes in the initial conformation of the HPAM additives. Initially collapsed, random-coiling conformations exhibited Newtonian laminar flow and Type-A turbulent drag reduction, while initially extended conformations exhibited shear-thinning in laminar flow and Type-B turbulent drag reduction. The gross-flow physics of Type-B drag reduction were delineated. A characteristic "ladder" structure prevailed, with polymeric regime segments that were roughly parallel to, but shifted upward from, the Prandtl-Karman line. In the polymeric regime, both Type-A fan and Type -B ladder structures were essentially independent of pipe diameter, and were scaled by the wall shear stress. The wall shear stress also scaled degradation during drag reduction. New onset and slope increment correlations were presented for Type-A drag reduction by HPAM additives. In Type-B drag reduction, flow enhancement was found proportional to additive concentration, and the intrinsic slip, Sigma = S^'/(c/M _{rm w}), varied roughly as the third power of backbone chain links N_ {rm bb}. New intrinsic slip and retro-onset correlations were presented for Type-B drag reduction by HPAM additives. Analysis of Type-B literature revealed a wide range of additive efficacies, with specific slips S^'/c from 0.0001 to 4. For the most effective additives, HPAM and asbestos fibers, the additive-pervaded volume fraction per unit flow enhancement, X_{rm v} /S^' ~ 3000, implied that these additives align during drag reduction. The slip ratio R_{rm sc}, which is the relative flow enhancement induced in Type-A and Type-B drag reduction at constant additive concentration, was found to be a universal function of the normalized turbulent flow strength (Re_ {rm s}sqrtf/Re_ {rm s}sqrtf*). The extension of initially collapsed, random-coiling, HPAM macromolecules by the turbulent flow field thus seems independent of additive parameters and absolute wall shear stress levels. Gross flow additive equivalence was detected at iso-slip points, where different polymer solutions induced equal flow enhancements. At numerous such points, the collapsed to extended slip ratio at constant concentration, R_{rm sc}, was essentially equal to the extended to collapsed concentration ratio at constant slip, R _{rm cs}. Thus, for fixed total additive concentration, the R_{ rm sc} observed at any Re_ {rm s}sqrtf simply represents the fraction of originally collapsed macromolecules that have become extended in the flow, and thence effective in drag reduction. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617 -253-5668; Fax 617-253-1690.).

  1. V1 orientation plasticity is explained by broadly tuned feedforward inputs and intracortical sharpening.

    PubMed

    Teich, Andrew F; Qian, Ning

    2010-03-01

    Orientation adaptation and perceptual learning change orientation tuning curves of V1 cells. Adaptation shifts tuning curve peaks away from the adapted orientation, reduces tuning curve slopes near the adapted orientation, and increases the responses on the far flank of tuning curves. Learning an orientation discrimination task increases tuning curve slopes near the trained orientation. These changes have been explained previously in a recurrent model (RM) of orientation selectivity. However, the RM generates only complex cells when they are well tuned, so that there is currently no model of orientation plasticity for simple cells. In addition, some feedforward models, such as the modified feedforward model (MFM), also contain recurrent cortical excitation, and it is unknown whether they can explain plasticity. Here, we compare plasticity in the MFM, which simulates simple cells, and a recent modification of the RM (MRM), which displays a continuum of simple-to-complex characteristics. Both pre- and postsynaptic-based modifications of the recurrent and feedforward connections in the models are investigated. The MRM can account for all the learning- and adaptation-induced plasticity, for both simple and complex cells, while the MFM cannot. The key features from the MRM required for explaining plasticity are broadly tuned feedforward inputs and sharpening by a Mexican hat intracortical interaction profile. The mere presence of recurrent cortical interactions in feedforward models like the MFM is insufficient; such models have more rigid tuning curves. We predict that the plastic properties must be absent for cells whose orientation tuning arises from a feedforward mechanism.

  2. Preliminary in vivo efficacy studies of a recombinant rhesus anti-alpha(4)beta(7) monoclonal antibody.

    PubMed

    Pereira, L E; Onlamoon, N; Wang, X; Wang, R; Li, J; Reimann, K A; Villinger, F; Pattanapanyasat, K; Mori, K; Ansari, A A

    2009-01-01

    Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.

  3. Pyruvate Administration Reduces Recurrent/Moderate Hypoglycemia-Induced Cortical Neuron Death in Diabetic Rats

    PubMed Central

    Choi, Bo Young; Kim, Jin Hee; Kim, Hyun Jung; Yoo, Jin Hyuk; Song, Hong Ki; Sohn, Min; Won, Seok Joon; Suh, Sang Won

    2013-01-01

    Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p.) injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10U/kg, i.p.) without anesthesia for five consecutive days. Pyruvate (500mg/kg) was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation. PMID:24278448

  4. Stable azodye photo-alignment layer for liquid crystal devices achieved by "turning off" dye photosensitivity

    NASA Astrophysics Data System (ADS)

    McGinty, C.; Finnemeyer, V.; Reich, R.; Clark, H.; Berry, S.; Bos, P.

    2017-11-01

    We have previously proposed a low cost, versatile process for stabilizing azodye photo-alignment layers for liquid crystal devices by utilizing a surface localized reactive mesogen (RM) layer. The RM is applied by dissolving the monomer in a liquid crystal material prior to filling the cell. In this paper, we show the significant effect of azodye layer thickness on the long term stability of these alignment layers when exposed to polarized light. We demonstrate, surprisingly, that thin azodye layers (˜3 nm) provide improved stability over thicker (˜40 nm) layers. Using this process, we show cells which have been stable to exposure with polarized light through one month. Additionally, we demonstrate the use of a photo-alignment layer to align the liquid crystals that afterwards can be rendered insensitive to polarized light. This was accomplished by using the process described above with the additional step of eliminating the photosensitivity of the azodye layer through photo-bleaching; the result is an RM alignment layer that will be stable when exposed to polarized light in the dye absorption band.

  5. CENL1 Expression in the Rib Meristem Affects Stem Elongation and the Transition to Dormancy in Populus[W][OA

    PubMed Central

    Ruonala, Raili; Rinne, Päivi L.H.; Kangasjärvi, Jaakko; van der Schoot, Christiaan

    2008-01-01

    We investigated the short day (SD)–induced transition to dormancy in wild-type hybrid poplar (Populus tremula × P. tremuloides) and its absence in transgenic poplar overexpressing heterologous PHYTOCHROME A (PHYA). CENTRORADIALIS-LIKE1 (CENL1), a poplar ortholog of Arabidopsis thaliana TERMINAL FLOWER1 (TFL1), was markedly downregulated in the wild-type apex coincident with SD-induced growth cessation. By contrast, poplar overexpressing a heterologous Avena sativa PHYA construct (P35S:AsPHYA), with PHYA accumulating in the rib meristem (RM) and adjacent tissues but not in the shoot apical meristem (SAM), upregulated CENL1 in the RM area coincident with an acceleration of stem elongation. In SD-exposed heterografts, both P35S:AsPHYA and wild-type scions ceased growth and formed buds, whereas only the wild type assumed dormancy and P35S:AsPHYA showed repetitive flushing. This shows that the transition is not dictated by leaf-produced signals but dependent on RM and SAM properties. In view of this, callose-enforced cell isolation in the SAM, associated with suspension of indeterminate growth during dormancy, may require downregulation of CENL1 in the RM. Accordingly, upregulation of CENL1/TFL1 might promote stem elongation in poplar as well as in Arabidopsis during bolting. Together, the results suggest that the RM is particularly sensitive to photoperiodic signals and that CENL1 in the RM influences transition to dormancy in hybrid poplar. PMID:18192437

  6. How would the ocean carbon cycle be affected by radiation management geoengineering?

    NASA Astrophysics Data System (ADS)

    Lauvset, Siv K.; Tjiputra, Jerry; Muri, Helene; Grini, Alf

    2017-04-01

    Human emissions of carbon dioxide to the atmosphere is unequivocally causing global warming and climate change (IPCC, 2013). At the 21st United Nations Framework Convention on climate Change (UNFCCC) Conference of the Parties it was agreed to limit the increase in global average temperature to 2˚C above pre-industrial levels. We have used the Norwegian Earth System Model (NorESM1-ME) and applied radiation management (RM) methods in order to bring the future radiative forcing change in the RCP8.5 CO2 emission scenario in line with that of the RCP4.5 CO2 emission scenario. Three different RM methods, with varying effects on atmospheric physics, were used in these experiments: stratospheric aerosol injection (SAI); marine sky brightening (MSB); and cirrus cloud thinning (CCT). Here we will present how the different methods affect the ocean carbon cycle, which is a well-known and important feedback on climate change. In particular, we focus on changes to the ocean primary production, which are known to be spatially and temporally complex. We show that while the global mean temperature when applying RM is similar to that in the RCP4.5 scenario, no RM method produce similar ocean primary production as in the RCP4.5 scenario. Our simulations indicate that when it comes to the ocean primary productivity there will be regional winners and losers. The different RM methods also produce spatially very different results, partly linked to how the different RM methods affect clouds. The results of this work does nothing to diminish the complexity of climate impacts on primary production, but rather highlights that any change in ocean primary production is driven by a combination of several parameters, which all change in different ways. The experiments highlight the, at present, uncertain changes to ocean productivity in the future and highlights the caution necessary before additional human perturbations to the Earth system is attempted.

  7. Weak-lensing mass calibration of redMaPPer galaxy clusters in Dark Energy Survey Science Verification data

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

    Melchior, P.; Gruen, D.; McClintock, T.

    We use weak-lensing shear measurements to determine the mean mass of optically selected galaxy clusters in Dark Energy Survey Science Verification data. In a blinded analysis, we split the sample of more than 8,000 redMaPPer clusters into 15 subsets, spanning ranges in the richness parametermore » $$5 \\leq \\lambda \\leq 180$$ and redshift $$0.2 \\leq z \\leq 0.8$$, and fit the averaged mass density contrast profiles with a model that accounts for seven distinct sources of systematic uncertainty: shear measurement and photometric redshift errors; cluster-member contamination; miscentering; deviations from the NFW halo profile; halo triaxiality; and line-of-sight projections. We combine the inferred cluster masses to estimate the joint scaling relation between mass, richness and redshift, $$\\mathcal{M}(\\lambda,z) \\varpropto M_0 \\lambda^{F} (1+z)^{G}$$. We find $$M_0 \\equiv \\langle M_{200\\mathrm{m}}\\,|\\,\\lambda=30,z=0.5\\rangle=\\left[ 2.35 \\pm 0.22\\ \\rm{(stat)} \\pm 0.12\\ \\rm{(sys)} \\right] \\cdot 10^{14}\\ M_\\odot$$, with $$F = 1.12\\,\\pm\\,0.20\\ \\rm{(stat)}\\, \\pm\\, 0.06\\ \\rm{(sys)}$$ and $$G = 0.18\\,\\pm\\, 0.75\\ \\rm{(stat)}\\, \\pm\\, 0.24\\ \\rm{(sys)}$$. The amplitude of the mass-richness relation is in excellent agreement with the weak-lensing calibration of redMaPPer clusters in SDSS by Simet et al. (2016) and with the Saro et al. (2015) calibration based on abundance matching of SPT-detected clusters. Our results extend the redshift range over which the mass-richness relation of redMaPPer clusters has been calibrated with weak lensing from $$z\\leq 0.3$$ to $$z\\leq0.8$$. Calibration uncertainties of shear measurements and photometric redshift estimates dominate our systematic error budget and require substantial improvements for forthcoming studies.« less

  8. Long-Term Anesthetic-Dependent Hypoactivity after Repetitive Mild Traumatic Brain Injuries in Adolescent Mice.

    PubMed

    Semple, Bridgette D; Sadjadi, Raha; Carlson, Jaclyn; Chen, Yiran; Xu, Duan; Ferriero, Donna M; Noble-Haeusslein, Linda J

    2016-01-01

    Recent evidence supports the hypothesis that repetitive mild traumatic brain injuries (rmTBIs) culminate in neurological impairments and chronic neurodegeneration, which have wide-ranging implications for patient management and return-to-play decisions for athletes. Adolescents show a high prevalence of sports-related head injuries and may be particularly vulnerable to rmTBIs due to ongoing brain maturation. However, it remains unclear whether rmTBIs, below the threshold for acute neuronal injury or symptomology, influence long-term outcomes. To address this issue, we first defined a very mild injury in adolescent mice (postnatal day 35) as evidenced by an increase in Iba-1- labeled microglia in white matter in the acutely injured brain, in the absence of indices of cell death, axonal injury, and vasogenic edema. Using this level of injury severity and Avertin (2,2,2-tribromoethanol) as the anesthetic, we compared mice subjected to either a single mTBI or 2 rmTBIs, each separated by 48 h. Neurobehavioral assessments were conducted at 1 week and at 1 and 3 months postimpact. Mice subjected to rmTBIs showed transient anxiety and persistent and pronounced hypoactivity compared to sham control mice, alongside normal sensorimotor, cognitive, social, and emotional function. As isoflurane is more commonly used than Avertin in animal models of TBI, we next examined long-term outcomes after rmTBIs in mice that were anesthetized with this agent. However, there was no evidence of abnormal behaviors even with the addition of a third rmTBI. To determine whether isoflurane may be neuroprotective, we compared the acute pathology after a single mTBI in mice anesthetized with either Avertin or isoflurane. Pathological findings were more pronounced in the group exposed to Avertin compared to the isoflurane group. These collective findings reveal distinct behavioral phenotypes (transient anxiety and prolonged hypoactivity) that emerge in response to rmTBIs. Our findings further suggest that selected anesthetics may confer early neuroprotection after rmTBIs, and as such mask long-term abnormal phenotypes that may otherwise emerge as a consequence of acute pathogenesis. © 2016 S. Karger AG, Basel.

  9. Enhanced Polarized Emission from the One-parsec-scale Hotspot of 3C 84 as a Result of the Interaction with the Clumpy Ambient Medium

    NASA Astrophysics Data System (ADS)

    Nagai, H.; Fujita, Y.; Nakamura, M.; Orienti, M.; Kino, M.; Asada, K.; Giovannini, G.

    2017-11-01

    We present Very Long Baseline Array polarimetric observations of the innermost jet of 3C 84 (NGC 1275) at 43 GHz. A significant polarized emission is detected at the hotspot of the innermost restarted jet, which is located 1 pc south from the radio core. While the previous report presented a hotspot at the southern end of the western limb, the hotspot location has been moved to the southern end of the eastern limb. Faraday rotation is detected within an entire bandwidth of the 43 GHz band. The measured rotation measure (RM) is at most (6.3 ± 1.9) × 105 rad m-2 and might be slightly time variable on the timescale of a month by a factor of a few. Our measured RM and the RM previously reported by the CARMA and SMA observations cannot be consistently explained by the spherical accretion flow with a power-law profile. We propose that a clumpy/inhomogeneous ambient medium is responsible for the observed RM. Using an equipartition magnetic field, we derive the electron density of 2 × 104 cm-3. Such an electron density is consistent with the cloud of the narrow line emission region around the central engine. We also discuss the magnetic field configuration from the black hole scale to the parsec scale and the origin of low polarization.

  10. U.S. Army Recruiting for the Global War on Terror and Beyond

    DTIC Science & Technology

    2006-03-15

    marketing and advertising budget is allocated to this effort.78 “Walk Ins” and “Call Ins” (those interested Americans who make contact...Congressional Support 2. National Marketing and Advertising OCPA(+) ARMY BRAND GP/AAC AAC(+) OCLL(+) R ec ru it in g In tr a- A rm y C o o rd in at io n...G ro u p RIACG (Lines of Operation) USAREC(+) USAREC(+) USACFSC FIGURE 4 The National Marketing and Advertising Line of Operation

  11. Symbolic Image Understanding

    DTIC Science & Technology

    1991-11-01

    publication. APPROVED: a LEE A. UVANNI Project Engineer FOR THE COMMANDER: GARRY W. BARRINGER Technical Director Intelligence & Reconnaissance...f Od1cAtl nd ir-’bm a UNl tofU~rtaw ."t Pu’ o scrxr± ing twra fa revrl r Jt,= seagrg d un zla souLces gahwtW" r T , iUm rm , rruk4 c adiwvctws coa w...1990j matches straight lines extracted from an image with model lines r projected to the image plane using an assumed location of the camera. This

  12. Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

    PubMed

    Gimenez-Rivera, Vladimir-Andrey; Siebenhaar, Frank; Zimmermann, Carolin; Siiskonen, Hanna; Metz, Martin; Maurer, Marcus

    2016-12-01

    Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient Kit W-sh/W-sh (Sash) and MCPT5-Cre + iDTR + mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8 + tissue-resident memory T (T RM ) cells. The CD8 + T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous T RM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8 + T RM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. Depolarization of surface-attached hypothalamic mouse neurons studied by acoustic wave (thickness shear mode) detector.

    PubMed

    Cheung, Shilin; Fick, Laura J; Belsham, Denise D; Thompson, Michael

    2010-02-01

    Isolation of neurons from animal tissue is an important aspect of understanding basic biochemical processes such as the action of hormones and neurotransmitters. In the present work, the focus is on an effort to evaluate the utility of acoustic wave physics for the study of such cells. Immortalised hypothalamic neuronal cells from mouse embryos were cultured on the surface of the gold electrode of a 9.0 MHz thickness-shear mode acoustic wave sensor. These cells, which are clonal, are imposed on the surface of the device at a confluence in the range of 80-100%. The coated sensor is incorporated into a flow-injection configuration such that electrolytes can be introduced in order to examine their effects through measurement by network analysis. Both series resonance frequency, fs, and motional resistance, R(m), were measured in a number of experiments involving the injection of KCl and NaCl into the sensor-neuron system. The various responses to these electrolytes were interpreted in terms of changes in cellular structure associated with the depolarization process. The sensor-neuron system was found to elicit different responses to the addition of KCl and NaCl. Preliminary findings indicate that the TSM sensor does not purely measure changes in the membrane potential upon KCl addition. Typical changes in fs for 15 mM, 30 mM and 60 mM KCl additions were 54 +/- 15, 80 +/- 26 and 142 +/- 58 Hz (mean +/- standard deviation) respectively. Typical changes in R(m) for these KCl additions were 7 +/- 3, 13 +/- 4 and 23 +/- 6 Omega, respectively. These results were concluded after 17 runs at each concentration. Despite the large relative standard deviations, the dependence of f(s) and R(m) with respect to concentration was apparent. Controls performed by coating the TSM sensor with laminin or a cell attachment matrix showed no significant changes in either f(s) or R(m) for the same solutions tested on the sensor-neuron system.

  14. In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection

    PubMed Central

    Takahashi, Yoshiaki; Byrareddy, Siddappa N.; Albrecht, Christina; Brameier, Markus; Walter, Lutz; Mayne, Ann E.; Dunbar, Paul; Russo, Robert; Little, Dawn M.; Villinger, Tara; Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Villinger, Francois; Ansari, Aftab A.

    2014-01-01

    The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8+ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4+ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a+ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses. PMID:24603870

  15. Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.

    PubMed

    Fu, Jingjing; Zhang, Lingling; Song, Shanshan; Sheng, Kangliang; Li, Ying; Li, Peipei; Song, Shasha; Wang, Qingtong; Chu, Jianhong; Wei, Wei

    2014-05-01

    To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels. BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice. BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.

  16. Sonar Imaging of Elastic Fluid-Filled Cylindrical Shells.

    NASA Astrophysics Data System (ADS)

    Dodd, Stirling Scott

    1995-01-01

    Previously a method of describing spherical acoustic waves in cylindrical coordinates was applied to the problem of point source scattering by an elastic infinite fluid -filled cylindrical shell (S. Dodd and C. Loeffler, J. Acoust. Soc. Am. 97, 3284(A) (1995)). This method is applied to numerically model monostatic oblique incidence scattering from a truncated cylinder by a narrow-beam high-frequency imaging sonar. The narrow beam solution results from integrating the point source solution over the spatial extent of a line source and line receiver. The cylinder truncation is treated by the method of images, and assumes that the reflection coefficient at the truncation is unity. The scattering form functions, calculated using this method, are applied as filters to a narrow bandwidth, high ka pulse to find the time domain scattering response. The time domain pulses are further processed and displayed in the form of a sonar image. These images compare favorably to experimentally obtained images (G. Kaduchak and C. Loeffler, J. Acoust. Soc. Am. 97, 3289(A) (1995)). The impact of the s_{ rm o} and a_{rm o} Lamb waves is vividly apparent in the images.

  17. Biochemical characterization of a novel L-Asparaginase with low glutaminase activity from Rhizomucor miehei and its application in food safety and leukemia treatment.

    PubMed

    Huang, Linhua; Liu, Yu; Sun, Yan; Yan, Qiaojuan; Jiang, Zhengqiang

    2014-03-01

    A novel fungal gene encoding the Rhizomucor miehei l-asparaginase (RmAsnase) was cloned and expressed in Escherichia coli. Its deduced amino acid sequence shared only 57% identity with the amino acid sequences of other reported l-asparaginases. The purified l-asparaginase homodimer had a molecular mass of 133.7 kDa, a high specific activity of 1,985 U/mg, and very low glutaminase activity. RmAsnase was optimally active at pH 7.0 and 45°C and was stable at this temperature for 30 min. The final level of acrylamide in biscuits and bread was decreased by about 81.6% and 94.2%, respectively, upon treatment with 10 U RmAsnase per mg flour. Moreover, this l-asparaginase was found to potentiate a lectin's induction of leukemic K562 cell apoptosis, allowing lowering of the drug dosage and shortening of the incubation time. Overall, our findings suggest that RmAsnase possesses a remarkable potential for the food industry and in chemotherapeutics for leukemia.

  18. Biochemical Characterization of a Novel l-Asparaginase with Low Glutaminase Activity from Rhizomucor miehei and Its Application in Food Safety and Leukemia Treatment

    PubMed Central

    Huang, Linhua; Liu, Yu; Sun, Yan

    2014-01-01

    A novel fungal gene encoding the Rhizomucor miehei l-asparaginase (RmAsnase) was cloned and expressed in Escherichia coli. Its deduced amino acid sequence shared only 57% identity with the amino acid sequences of other reported l-asparaginases. The purified l-asparaginase homodimer had a molecular mass of 133.7 kDa, a high specific activity of 1,985 U/mg, and very low glutaminase activity. RmAsnase was optimally active at pH 7.0 and 45°C and was stable at this temperature for 30 min. The final level of acrylamide in biscuits and bread was decreased by about 81.6% and 94.2%, respectively, upon treatment with 10 U RmAsnase per mg flour. Moreover, this l-asparaginase was found to potentiate a lectin's induction of leukemic K562 cell apoptosis, allowing lowering of the drug dosage and shortening of the incubation time. Overall, our findings suggest that RmAsnase possesses a remarkable potential for the food industry and in chemotherapeutics for leukemia. PMID:24362429

  19. Marker-assisted introgression of broad-spectrum blast resistance genes into the cultivated MR219 rice variety.

    PubMed

    Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

    2017-07-01

    The rice cultivar MR219 is famous for its better yield and long and fine grain quality; however, it is susceptible to blast disease. The main objective of this study was to introgress blast resistance genes into MR219 through marker-assisted selection (MAS). The rice cultivar MR219 was used as the recurrent parent, and Pongsu Seribu 1 was used as the donor. Marker-assisted foreground selection was performed using RM6836 and RM8225 to identify plants possessing blast resistance genes. Seventy microsatellite markers were used to estimate recurrent parent genome (RPG) recovery. Our analysis led to the development of 13 improved blast resistant lines with Piz, Pi2 and Pi9 broad-spectrum blast resistance genes and an MR219 genetic background. The RPG recovery of the selected improved lines was up to 97.70% with an average value of 95.98%. Selected improved lines showed a resistance response against the most virulent blast pathogen pathotype, P7.2. The selected improved lines did not express any negative effect on agronomic traits in comparison with MR219. The research findings of this study will be a conducive approach for the application of different molecular techniques that may result in accelerating the development of new disease-resistant rice varieties, which in turn will match rising demand and food security worldwide. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  20. a Combined Molecular Dynamics and NMR Spectroscopic Protocol for the Conformational Analysis of Oligosaccharides.

    NASA Astrophysics Data System (ADS)

    Varma, Vikram

    A combined experimental and theoretical protocol for the conformational analysis of oligosaccharides is presented. Three disaccharides, methyl alpha - scD-mannopyranosyl-(1 to 3)-alpha- scD-mannopyranoside, methyl beta- scD-galactopyranosyl-(1 to 4)-beta- scD-glucopyranoside, and propyl beta- scD-2-acetamido -2-deoxy glucopyranosyl-(1 to 3)- alpha- scL-rhamnopyranoside, are used to evaluate a protocol for conformational analysis that makes use of molecular dynamics calculations with the CHARMM force field. Dynamics trajectories computed in vacuo and in water are used to calculate time-averaged NMR parameters such as spin-lattice relaxation times (T_1 ), Nuclear Overhauser Enhancements (NOE), and heteronuclear spin-spin coupling constants (^3J _{rm CH}). The calculated NMR parameters are then compared to experimental values and used to evaluate the computational procedure. The energetically accessible conformations are effectively sampled by the simulations. The method has been extended to the conformational analysis of higher-order oligosaccharides corresponding to the cell-wall polysaccharide of the Streptococcus Group A, and the Shigella flexneri Y O-antigen. The Streptococcus Group A cell-wall polysaccharide is comprised of a backbone of rhamnopyranosyl units connected by alternating alpha- scL-(1 to 3) and alpha- scL -(1 to 2) linkages, to which are attached N-acetyl-beta- scD-glucosamine ( beta- scD-GlcpNAc) residues at the 3 positions of the rhamnose backbone.rm A&rm B^'qquad A^'& rm Bqquad Acr[{-alpha}{-}L{-}Rha {it p}{-}(1to2){-alpha }{-}L{-}Rha{it p} {-}(1to3){-alpha}{ -}L{-}Rha{it p}-(1to2) -alpha-L-Rha{it p}{-}(1 to3){-alpha}{-}L{- }Rha{it p}{-}cr&uparrow(1 to3)&uparrow(1to3)crbeta {-}D{-}&rm Glc{it p }NAcqquadbeta{-}D{-}& rm Glc{it p}NAccr&rm C ^'&rm C] A branched trisaccharide (A^' -(C)B), a tetrasaccharide (A^' -(C)B-A), a pentasaccharide (C^' -B^'-A ^'-(C)B), and two hexasaccharides (C^'-B^ '-A^' -(C)B-A) and (A-(C^')B ^'-A^' -(C)B), have been chosen for study. The Shigella flexneri Y O-antigen is a linear polysaccharide that is composed of rhamnose units linked alpha- scL-(1 to 3) and alpha- scL-(1 to 2), interspersed by N-acetyl-beta - scD-glucosamine (beta- scD -GlcpNAc) to form a periodic repeating unit ABCD. &rm A&rm B&rm C&rm Dcr [{-alpha}{-}L {-}Rha{it p}-(1to2){ -alpha}{-}L{-}Rha{it p}{-}(1to3){-alpha} {-}L{-}Rha{it p}{ -}(1to3){-}beta{-}D {-}Glc{it p}NAc{-}(1 to2){-}]_{it n}A heptasaccharide corresponding to the fragment (ABCDA^'B ^'C^' ) of the Shigella flexneri Y polysaccharide has been investigated. The conformational properties of all of the oligosaccharides have been studied using molecular dynamics simulations. Interproton distances derived from ROESY spectra are used to determine the starting conformations of the oligosaccharides used in the dynamics calculations, and dynamics simulations are computed with proton pairs constrained to the ROESY -derived distances, as well as with the constraints removed. These dynamics trajectories are used to calculate ROESY buildup curves with CROSREL, a program that treats cross relaxation by means of a full matrix relaxation approach. The calculated buildup curves compare favorably with the experimental buildup curves. The study demonstrates that molecular dynamics, in conjunction with NMR spectroscopy, can be a useful tool in the understanding of the conformational behavior of oligosaccharides in solution. The results provide a model for antigen topology that can be used to infer some of the critical features of antibody-antigen interactions.

  1. Impact of 10-Minute Interval Roller Massage on Performance and Active Range of Motion.

    PubMed

    Hodgson, D D; Quigley, P J; Whitten, J H D; Reid, J C; Behm, David G

    2017-11-16

    Hodgson, DD, Quigley, PJ, Whitten, JHD, Reid, JC, and Behm, DG. Impact of 10-minute interval roller massage on performance and active range of motion. J Strength Cond Res XX(X): 000-000, 2017-Roller massage (RM) has been shown to increase range of motion (ROM) without subsequent performance deficits. However, prolonged static stretching (SS) can induce performance impairments. The objective of this study was to examine the effects of combining SS and RM with and without subsequent RM on ROM and neuromuscular performance. Subjects (n = 12) participated in 5 sessions: (a) SS only (SS_rest), (b) SS + RM (SS + RM_rest), (c) SS with RM at 10 and 20 minutes after stretch (SS_RM), (d) SS + RM with RM at 10 and 20 minutes after stretch (SS + RM_RM), and (e) control. For the SS conditions, the quadriceps and hamstrings received passive SS for 2 × 30 seconds each. For the SS + RM conditions, SS was applied to the quadriceps and hamstrings for 30 seconds each, and RM was performed for 30 seconds per muscle. SS_RM and SS + RM_RM conditions received an additional 30-second RM at 10 and 20 minutes after warm-up, whereas sessions without additional RM rested for the same duration. Testing measures included hip flexion (HF) and knee flexion (KF) active and passive ROM, hurdle jump height and contact time, countermovement jump height, and maximal voluntary isometric contraction force. Initial KF and HF ROM improvements provided by SS_RM and SS + RM_RM were sustained up to 30 minutes after intervention. Furthermore, SS_RM exhibited greater ROM compared with sessions lacking additional RM in active and passive HF as well as active and passive KF. Similarly, SS + RM_RM elicited greater KF and HF ROM improvements than SS_rest. In conclusion, active KF and HF ROM improvements were prolonged by additional RM, whereas neuromuscular performance remained relatively unaffected.

  2. Fluorescence imaging of reactive oxygen species by confocal laser scanning microscopy for track analysis of synchrotron X-ray photoelectric nanoradiator dose: X-ray pump-optical probe.

    PubMed

    Jeon, Jae Kun; Han, Sung Mi; Kim, Jong Ki

    2016-09-01

    Bursts of emissions of low-energy electrons, including interatomic Coulomb decay electrons and Auger electrons (0-1000 eV), as well as X-ray fluorescence produced by irradiation of large-Z element nanoparticles by either X-ray photons or high-energy ion beams, is referred to as the nanoradiator effect. In therapeutic applications, this effect can damage pathological tissues that selectively take up the nanoparticles. Herein, a new nanoradiator dosimetry method is presented that uses probes for reactive oxygen species (ROS) incorporated into three-dimensional gels, on which macrophages containing iron oxide nanoparticles (IONs) are attached. This method, together with site-specific irradiation of the intracellular nanoparticles from a microbeam of polychromatic synchrotron X-rays (5-14 keV), measures the range and distribution of OH radicals produced by X-ray emission or superoxide anions ({\\rm{O}}_2^-) produced by low-energy electrons. The measurements are based on confocal laser scanning of the fluorescence of the hydroxyl radical probe 2-[6-(4'-amino)phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF) or the superoxide probe hydroethidine-dihydroethidium (DHE) that was oxidized by each ROS, enabling tracking of the radiation dose emitted by the nanoradiator. In the range 70 µm below the irradiated cell, ^\\bullet{\\rm{OH}} radicals derived mostly from either incident X-ray or X-ray fluorescence of ION nanoradiators are distributed along the line of depth direction in ROS gel. In contrast, {\\rm{O}}_2^- derived from secondary electron or low-energy electron emission by ION nanoradiators are scattered over the ROS gel. ROS fluorescence due to the ION nanoradiators was observed continuously to a depth of 1.5 mm for both oxidized APF and oxidized DHE with relatively large intensity compared with the fluorescence caused by the ROS produced solely by incident primary X-rays, which was limited to a depth of 600 µm, suggesting dose enhancement as well as more penetration by nanoradiators. In conclusion, the combined use of a synchrotron X-ray microbeam-irradiated three-dimensional ROS gel and confocal laser scanning fluorescence microscopy provides a simple dosimetry method for track analysis of X-ray photoelectric nanoradiator radiation, suggesting extensive cellular damage with dose-enhancement beyond a single cell containing IONs.

  3. Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease.

    PubMed

    Gorton, Davina; Sikder, Suchandan; Williams, Natasha L; Chilton, Lisa; Rush, Catherine M; Govan, Brenda L; Cunningham, Madeleine W; Ketheesan, Natkunam

    2016-12-01

    Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly, we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeated exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection.

  4. Searching for the fastest dynamo: laminar ABC flows.

    PubMed

    Alexakis, Alexandros

    2011-08-01

    The growth rate of the dynamo instability as a function of the magnetic Reynolds number R(M) is investigated by means of numerical simulations for the family of the Arnold-Beltrami-Childress (ABC) flows and for two different forcing scales. For the ABC flows that are driven at the largest available length scale, it is found that, as the magnetic Reynolds number is increased: (a) The flow that results first in a dynamo is the 2 1/2-dimensional flow for which A=B and C=0 (and all permutations). (b) The second type of flow that results in a dynamo is the one for which A=B≃2C/5 (and permutations). (c) The most symmetric flow, A=B=C, is the third type of flow that results in a dynamo. (d) As R(M) is increased, the A=B=C flow stops being a dynamo and transitions from a local maximum to a third-order saddle point. (e) At larger R(M), the A=B=C flow reestablishes itself as a dynamo but remains a saddle point. (f) At the largest examined R(M), the growth rate of the 2 1/2-dimensional flows starts to decay, the A=B=C flow comes close to a local maximum again, and the flow A=B≃2C/5 (and permutations) results in the fastest dynamo with growth rate γ≃0.12 at the largest examined R(M). For the ABC flows that are driven at the second largest available length scale, it is found that (a) the 2 1/2-dimensional flows A=B,C=0 (and permutations) are again the first flows that result in a dynamo with a decreased onset. (b) The most symmetric flow, A=B=C, is the second type of flow that results in a dynamo. It is, and it remains, a local maximum. (c) At larger R(M), the flow A=B≃2C/5 (and permutations) appears as the third type of flow that results in a dynamo. As R(M) is increased, it becomes the flow with the largest growth rate. The growth rates appear to have some correlation with the Lyapunov exponents, but constructive refolding of the field lines appears equally important in determining the fastest dynamo flow.

  5. Endometrial IL-1beta, IL-6 and TNF-alpha, mRNA expression in mares resistant or susceptible to post-breeding endometritis. Effects of estrous cycle, artificial insemination and immunomodulation.

    PubMed

    Fumuso, Elida; Giguère, Steeve; Wade, José; Rogan, Dragan; Videla-Dorna, Ignacio; Bowden, Raúl A

    2003-11-15

    Endometrial mRNA expression of the pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) was assessed in mares resistant (RM) or susceptible (SM) to persistent post-breeding endometritis (PPBE). Eight RM and eight SM, were selected based on reproductive records and functional tests out of a herd of 2,000 light cross-type mares. Three experiments were done to study transcription patterns in (i) basal conditions; (ii) after artificial insemination (AI); and (iii) after administration of an immunomodulator at time of artificial insemination. Endometrial biopsies were taken during consecutive cycles: (i) at estrus, when follicles reached 35 mm and at diestrus (7 +/- 1 days after ovulation); (ii) at 24 h post-AI, with dead semen (estrus) and in diestrus; (iii) at 24 h after treatment with a Mycobacterium phlei cell-wall extract (MCWE) preparation and AI (with dead semen), and at diestrus. mRNA expression was quantitated by real time PCR. Under basal conditions, SM had significantly higher mRNA expression of all cytokines in estrus and of IL-1beta and TNF-alpha in diestrus, compared to RM. After AI, there were no differences between RM and SM in estrus; however, mRNA expression for all three pro-inflammatory cytokines was higher than under basal conditions. In diestrus, RM showed significantly lower IL-1beta and TNF-alpha mRNA expression than SM. When MCWE was administered at time of AI, no differences between cytokine induction from RM and SM were found. Globally, mRNA expression for all three cytokines correlated well among themselves when expression was high. The present study showed that (i) in basal conditions RM had lower mRNA expression of pro-inflammatory cytokines than SM with no effect of estrous cycle; (ii) AI upregulated mRNA expression for all three cytokines in both RM and SM, with persistance in diestrus in the latter; (iii) treatment with MCWE at time of AI down-regulated mRNA expression of IL-1 with significant effects in SM which behaved like RM. Immunomodulation with MCWE could be of help in restoring homeostatic local inflammatory mechanisms, thus assisting in the prophylaxis of post-breeding endometritis in mares.

  6. Enhanced Polarized Emission from the One-parsec-scale Hotspot of 3C 84 as a Result of the Interaction with the Clumpy Ambient Medium

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

    Nagai, H.; Kino, M.; Fujita, Y.

    2017-11-01

    We present Very Long Baseline Array polarimetric observations of the innermost jet of 3C 84 (NGC 1275) at 43 GHz. A significant polarized emission is detected at the hotspot of the innermost restarted jet, which is located 1 pc south from the radio core. While the previous report presented a hotspot at the southern end of the western limb, the hotspot location has been moved to the southern end of the eastern limb. Faraday rotation is detected within an entire bandwidth of the 43 GHz band. The measured rotation measure (RM) is at most (6.3 ± 1.9) × 10{sup 5}more » rad m{sup −2} and might be slightly time variable on the timescale of a month by a factor of a few. Our measured RM and the RM previously reported by the CARMA and SMA observations cannot be consistently explained by the spherical accretion flow with a power-law profile. We propose that a clumpy/inhomogeneous ambient medium is responsible for the observed RM. Using an equipartition magnetic field, we derive the electron density of 2 × 10{sup 4} cm{sup −3}. Such an electron density is consistent with the cloud of the narrow line emission region around the central engine. We also discuss the magnetic field configuration from the black hole scale to the parsec scale and the origin of low polarization.« less

  7. Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy.

    PubMed

    O'Neal, Wesley T; Griffin, William F; Kent, Susan D; Faiz, Filza; Hodges, Jonathan; Vuncannon, Jackson; Virag, Jitka A I

    2014-01-01

    EphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy.

  8. Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy

    PubMed Central

    O'Neal, Wesley T.; Griffin, William F.; Kent, Susan D.; Faiz, Filza; Hodges, Jonathan; Vuncannon, Jackson; Virag, Jitka A. I.

    2014-01-01

    EphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy. PMID:24795639

  9. Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

    PubMed

    Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

    2016-08-15

    In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. State-to-state dynamics of {\\rm{F}}({}^{2}{\\rm{P}})+{\\rm{HO}}({}^{2}{\\rm{\\Pi }})\\to {\\rm{O}}({}^{3}{\\rm{P}})+{\\rm{HF}}({}^{1}{\\rm{\\Sigma }}^{+}) reaction on {1}^{3}{{\\rm{A}}}^{\\prime\\prime} potential energy surface

    NASA Astrophysics Data System (ADS)

    Zhao, Juan; Wu, Hui; Sun, Hai-Bo; Wang, Li-Fei

    2018-02-01

    Not Available Project supported by the National Natural Science Foundation of China (Grant Nos. 11504206 and 11404049), the China Postdoctoral Science Foundation (CPSF) (Grant No. 2014M561259), and the Ph. D. Research Start-up Fund of Shandong Jiaotong University.

  11. Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15.

    PubMed

    Shaaban, Khaled A; Wang, Xiachang; Elshahawi, Sherif I; Ponomareva, Larissa V; Sunkara, Manjula; Copley, Gregory C; Hower, James C; Morris, Andrew J; Kharel, Madan K; Thorson, Jon S

    2013-09-27

    Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian Mountains of eastern Kentucky). High-resolution electrospray ionization mass spectrometry and ultraviolet absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1-3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A and D-F (1-3) displayed comparable binding affinities to the Hsp90α. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of nontoxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.

  12. SToRM: A Model for 2D environmental hydraulics

    USGS Publications Warehouse

    Simões, Francisco J. M.

    2017-01-01

    A two-dimensional (depth-averaged) finite volume Godunov-type shallow water model developed for flow over complex topography is presented. The model, SToRM, is based on an unstructured cell-centered finite volume formulation and on nonlinear strong stability preserving Runge-Kutta time stepping schemes. The numerical discretization is founded on the classical and well established shallow water equations in hyperbolic conservative form, but the convective fluxes are calculated using auto-switching Riemann and diffusive numerical fluxes. Computational efficiency is achieved through a parallel implementation based on the OpenMP standard and the Fortran programming language. SToRM’s implementation within a graphical user interface is discussed. Field application of SToRM is illustrated by utilizing it to estimate peak flow discharges in a flooding event of the St. Vrain Creek in Colorado, U.S.A., in 2013, which reached 850 m3/s (~30,000 f3 /s) at the location of this study.

  13. Planck intermediate results: XXXIV. The magnetic field structure in the Rosette Nebula

    DOE PAGES

    Aghanim, N.; Alves, M. I. R.; Arnaud, M.; ...

    2016-02-09

    Planck has mapped the polarized dust emission over the whole sky, making it possible to trace the Galactic magnetic field structure that pervades the interstellar medium (ISM). In this paper, we combine polarization data from Planck with rotation measure (RM) observations towards a massive star-forming region, the Rosette Nebula in the Monoceros molecular cloud, to study its magnetic field structure and the impact of an expanding H ii region on the morphology of the field. We derive an analytical solution for the magnetic field, assumed to evolve from an initially uniform configuration following the expansion of ionized gas and themore » formation of a shell of swept-up ISM. From the RM data we estimate a mean value of the line-of-sight component of the magnetic field of about 3 μG (towards the observer) in the Rosette Nebula, for a uniform electron density of about 12 cm -3. The dust shell that surrounds the Rosette H ii region is clearly observed in the Planck intensity map at 353 GHz, with a polarization signal significantly different from that of the local background when considered asa whole. The Planck observations constrain the plane-of-the-sky orientation of the magnetic field in the Rosette’s parent molecular cloud to be mostly aligned with the large-scale field along the Galactic plane. The Planck data are compared with the analytical model, which predicts the mean polarization properties of a spherical and uniform dust shell for a given orientation of the field. This comparison leads to an upper limit of about 45° on the angle between the line of sight and the magnetic field in the Rosette complex, for an assumed intrinsic dust polarization fraction of 4%. This field direction can reproduce the RM values detected in the ionized region if the magnetic field strength in the Monoceros molecular cloud is in the range 6.5–9 μG. Finally, the present analytical model is able to reproduce the RM distribution across the ionized nebula, as well as the mean dust polarization properties of the swept-up shell, and can be directly applied to other similar objects.« less

  14. Planck intermediate results: XXXIV. The magnetic field structure in the Rosette Nebula

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

    Aghanim, N.; Alves, M. I. R.; Arnaud, M.

    Planck has mapped the polarized dust emission over the whole sky, making it possible to trace the Galactic magnetic field structure that pervades the interstellar medium (ISM). In this paper, we combine polarization data from Planck with rotation measure (RM) observations towards a massive star-forming region, the Rosette Nebula in the Monoceros molecular cloud, to study its magnetic field structure and the impact of an expanding H ii region on the morphology of the field. We derive an analytical solution for the magnetic field, assumed to evolve from an initially uniform configuration following the expansion of ionized gas and themore » formation of a shell of swept-up ISM. From the RM data we estimate a mean value of the line-of-sight component of the magnetic field of about 3 μG (towards the observer) in the Rosette Nebula, for a uniform electron density of about 12 cm -3. The dust shell that surrounds the Rosette H ii region is clearly observed in the Planck intensity map at 353 GHz, with a polarization signal significantly different from that of the local background when considered asa whole. The Planck observations constrain the plane-of-the-sky orientation of the magnetic field in the Rosette’s parent molecular cloud to be mostly aligned with the large-scale field along the Galactic plane. The Planck data are compared with the analytical model, which predicts the mean polarization properties of a spherical and uniform dust shell for a given orientation of the field. This comparison leads to an upper limit of about 45° on the angle between the line of sight and the magnetic field in the Rosette complex, for an assumed intrinsic dust polarization fraction of 4%. This field direction can reproduce the RM values detected in the ionized region if the magnetic field strength in the Monoceros molecular cloud is in the range 6.5–9 μG. Finally, the present analytical model is able to reproduce the RM distribution across the ionized nebula, as well as the mean dust polarization properties of the swept-up shell, and can be directly applied to other similar objects.« less

  15. Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

    PubMed

    Xiao, Hanguang; Tan, Isabella; Butlin, Mark; Li, Decai; Avolio, Alberto P

    2018-03-01

    Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γ norm ) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γ norm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γ norm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γ norm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and reflection index as wave reflection indexes.

  16. Recruitment Maneuver Does not Increase the Risk of Ventilator Induced Lung Injury

    PubMed Central

    Akıncı, İbrahim Özkan; Atalan, Korkut; Tuğrul, Simru; Özcan, Perihan Ergin; Yılmazbayhan, Dilek; Kıran, Bayram; Basel, Ahmet; Telci, Lutfi; Çakar, Nahit

    2013-01-01

    Background: Mechanical ventilation (MV) may induce lung injury. Aims: To assess and evaluate the role of different mechanical ventilation strategies on ventilator-induced lung injury (VILI) in comparison to a strategy which includes recruitment manoeuvre (RM). Study design: Randomized animal experiment. Methods: Thirty male Sprague-Dawley rats were anaesthetised, tracheostomised and divided into 5 groups randomly according to driving pressures; these were mechanically ventilated with following peak alveolar opening (Pao) and positive end-expiratory pressures (PEEP) for 1 hour: Group 15-0: 15 cmH2O Pao and 0 cmH2O PEEP; Group 30-10: 30 cmH2O Pao and 10 cmH2O PEEP; Group 30-5: 30 cmH2O Pao and 5 cmH2O PEEP; Group 30-5&RM: 30 cmH2O Pao and 5 cmH2O PEEP with additional 45 cmH2O CPAP for 30 seconds in every 15 minutes; Group 45-0: 45 cmH2O Pao and 0 cmH2O PEEP Before rats were sacrificed, blood samples were obtained for the evaluation of cytokine and chemokine levels; then, the lungs were subsequently processed for morphologic evaluation. Results: Oxygenation results were similar in all groups; however, the groups were lined as follows according to the increasing severity of morphometric evaluation parameters: Group 15-0: (0±0.009) < Group 30-10: (0±0.14) < Group 30-5&RM: (1±0.12) < Group 30-5: (1±0.16) < Group 45-0: (2±0.16). Besides, inflammatory responses were the lowest in 30-5&RM group compared to all other groups. TNF-α, IL-1β, IL-6, MCP-1 levels were significantly different between group 30-5&RM and group 15-0 vs. group 45-0 in each group. Conclusion: RM with low PEEP reduces the risk of ventilator-induced lung injury with a lower release of systemic inflammatory mediators in response to mechanical ventilation. PMID:25207105

  17. High-Temperature High-Current Superconductors: Preparation, Structure, Superconducting Properties, and Flux-Pinning Mechanisms

    NASA Astrophysics Data System (ADS)

    Hu, Shouxiang

    In bulk high-T_{rm c } superconductors, weak links at the grain boundaries and weak flux pinning are the two major causes of low critical current density (J_{ rm c}) at 77 K. In the present study, various processes designed and developed to address these problems are discussed. The novel pressurized-partial -melt-growth process, which leads to a relatively large improvement in the microstructure as well as in the superconducting properties of bulk Y-Ba-Cu-O superconductors, is described. The effects of introducing foreign elements to serve as pinning centers are reported, and the associated anomalous superconducting phenomena are explained on the basis of a detailed study of basic pinning mechanisms related to the presence of small defects. It is demonstrated that in certain cases the pinning force induced by the compression of the vortex line may be comparable to, or even larger than, the usually recognized pinning force due to the condensation energy. Studies of the pinning mechanism corresponding to large boundary defects show that boundary defects associated with certain non-superconducting inclusions and isolated weak links have a very positive role in the enhancement of both the critical current density and the effective activation energy for flux creep. However, even optimized theoretical estimates show that it will be difficult to reach J_ {rm c} values of 5 times 10^5 A/cm^2 at 77 K and H = 1 T by increasing the number of Y_2BaCuO inclusions alone. Although even higher J_{rm c} values may be achieved by introducing other types of defects using alternative approaches such as irradiation, and, probably, chemical doping, the presence of large amount of boundary defects is very important in causing a large increase in the effective activation energy for flux creep. Also studied are the anisotropic electromagnetic features of the grain-aligned YBa_2Cu _3O_{rm x} bulk superconductors. The development of novel processing methods guided by improved understanding of the basic mechanisms involved opens the way for the preparation of high-quality bulk high-T_{rm c} superconducting materials for a wide variety of applications.

  18. REVERBERATION MAPPING WITH INTERMEDIATE-BAND PHOTOMETRY: DETECTION OF BROAD-LINE Hα TIME LAGS FOR QUASARS AT 0.2 < z < 0.4

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

    Jiang, Linhua; Shen, Yue; McGreer, Ian D.

    2016-02-20

    We present a reverberation mapping (RM) experiment that combines broad- and intermediate-band photometry; it is the first such attempt targeting 13 quasars at 0.2 < z < 0.9. The quasars were selected to have strong Hα or Hβ emission lines that are located in one of three intermediate bands (with FWHM around 200 Å) centered at 8045, 8505, and 9171 Å. The imaging observations were carried out in the intermediate bands and the broad i and z bands using the prime-focus imager 90Prime on the 2.3 m Bok telescope. Because of the large (∼1 deg{sup 2}) field of view (FOV) of 90Prime, we includedmore » the 13 quasars within only five telescope pointings or fields. The five fields were repeatedly observed over 20–30 epochs that were unevenly distributed over a duration of 5–6 months. The combination of the broad- and intermediate-band photometry allows us to derive accurate light curves for both optical continuum emission (from the accretion disk) and line emission (from the broad-line region, or BLR). We detect Hα time lags between the continuum and line emission in six quasars. These quasars are at relatively low redshifts 0.2 < z < 0.4. The measured lags are consistent with the current BLR size–luminosity relation for Hβ at z < 0.3. While this experiment appears successful in detecting lags of the bright Hα line, further investigation is required to see if it can also be applied to the fainter Hβ line for quasars at higher redshifts. Finally we demonstrate that, by using a small telescope with a large FOV, intermediate-band photometric RM can be efficiently executed for a large sample of quasars at z > 0.2.« less

  19. 75 FR 3230 - Sunshine Act Meeting Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ...-1051-000 ISO New England Inc. and New England Power Pool. E-8 RM08-7-002 Modification of Interchange... Systems Power Pool Inc. E-14 EL09-40-000 Southwest Power Pool, Inc. E-15 EL10-7-000 Power and Water... Section 23 of the Natural Gas Act. G-2 RP06-569-000, RP07-376-000 Transcontinental Gas Pipe Line...

  20. Simplified molecular input line entry system-based: QSAR modelling for MAP kinase-interacting protein kinase (MNK1).

    PubMed

    Begum, S; Achary, P Ganga Raju

    2015-01-01

    Quantitative structure-activity relationship (QSAR) models were built for the prediction of inhibition (pIC50, i.e. negative logarithm of the 50% effective concentration) of MAP kinase-interacting protein kinase (MNK1) by 43 potent inhibitors. The pIC50 values were modelled with five random splits, with the representations of the molecular structures by simplified molecular input line entry system (SMILES). QSAR model building was performed by the Monte Carlo optimisation using three methods: classic scheme; balance of correlations; and balance correlation with ideal slopes. The robustness of these models were checked by parameters as rm(2), r(*)m(2), [Formula: see text] and randomisation technique. The best QSAR model based on single optimal descriptors was applied to study in vitro structure-activity relationships of 6-(4-(2-(piperidin-1-yl) ethoxy) phenyl)-3-(pyridin-4-yl) pyrazolo [1,5-a] pyrimidine derivatives as a screening tool for the development of novel potent MNK1 inhibitors. The effects of alkyl group, -OH, -NO2, F, Cl, Br, I, etc. on the IC50 values towards the inhibition of MNK1 were also reported.

  1. X-ray Evidence for Ultra-Fast Outflows in Local AGNs

    NASA Astrophysics Data System (ADS)

    Tombesi, F.; Cappi, M.; Sambruna, R. M.; Reeves, J. N.; Reynolds, C. S.; Braito, V.; Dadina, M.

    2012-08-01

    X-ray evidence for ultra-fast outflows (UFOs) has been recently reported in a number of local AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts and 5 Broad-Line Radio Galaxies (BLRGs) observed with XMM-Newton and Suzaku. We detect UFOs in ga 40% of the sources. Their outflow velocities are in the range ˜ 0.03-0.3c, with a mean value of ˜ 0.14c. The ionization is high, in the range logℰ ˜3-6rm erg s-1 cm, and also the associated column densities are large, in the interval ˜ 1022-1024rm cm-2. Overall, these results point to the presence of highly ionized and massive outflowing material in the innermost regions of AGNs. Their variability and location on sub-pc scales favor a direct association with accretion disk winds/outflows. This also suggests that UFOs may potentially play a significant role in the AGN cosmological feedback besides jets, and their study can provide important clues on the connection between accretion disks, winds, and jets.

  2. Transmission electron microscopy study of microstructural properties and dislocation characterization in the GaN film grown on the cone-shaped patterned Al2O3 substrate.

    PubMed

    Park, Jung Sik; Yang, Jun-Mo; Park, Kyung Jin; Park, Yun Chang; Yoo, Jung Ho; Jeong, Chil Seong; Park, Jucheol; He, Yinsheng; Shin, Keesam

    2014-02-01

    Growing a GaN film on a patterned Al2O3 substrate is one of the methods of reducing threading dislocations (TDs), which can significantly deteriorate the performance of GaN-based LEDs. In this study, the microstructural details of the GaN film grown on a cone-shaped patterned Al2O3 substrate were investigated using high-resolution transmission electron microscopy and weak-beam dark-field techniques. Various defects such as misfit dislocations (MDs), recrystallized GaN (R-GaN) islands and nano-voids were observed on the patterned Al2O3 surfaces, i.e. the flat surface (FS), the inclined surface (IS) and the top surface (TS), respectively. Especially, the crystallographic orientation of R-GaN between the GaN film and the inclined Al2O3 substrate was identified as $[\\overline 1 2\\overline 1 0]_{{\\rm GaN}} \\hbox{//}[\\overline 1 101]_{{\\rm R - GaN} \\,{\\rm on}\\,{\\rm IS}} \\hbox{//}[\\overline 1 100]_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $, $(\\overline 1 012)_{{\\rm GaN}} \\hbox{//}(1\\overline 1 02)_{{\\rm R - Ga}\\,{\\rm Non}\\,{\\rm IS}} \\hbox{//}(\\overline {11} 26)_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $. In addition, a rotation by 9° between $(10\\overline 1 1)_{{\\rm R - GaN}} $ and $(0002)_{{\\rm GaN}} $ and between $(10\\overline 1 1)_{{\\rm R - GaN}} $ and $(0006)_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $ was found to reduce the lattice mismatch between the GaN film and the Al2O3 substrate. Many TDs in the GaN film were observed on the FS and TS of Al2O3. However, few TDs were observed on the IS. Most of the TDs generated from the FS of Al2O3 were bent to the inclined facet rather than propagating to the GaN surface, resulting in a reduction in the dislocation density. Most of the TDs generated from the TS of Al2O3 were characterized as edge dislocations.

  3. Feasibility of Renewable Energy Technology at the Afghanistan National Security University: A Site-Specific Study Focused on Potential Renewable Energy Technologies in Northwest Kabul, Afghanistan

    DTIC Science & Technology

    2011-04-26

    70% H2, O2 Proton exchange membrane fuel cell ( PEMFC ) Proton exchange membrane Rm temp to 80 °C 40–60% H2, O2, Air Direct methanol fuel cell...Cell PEMFC Proton Exchange Membrane Fuel Cell PV Photovoltaic SHGC Solar Heat Gain Coefficient SIR savings to investment ratio SOFC Solid Oxide

  4. A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells.

    PubMed

    Xia, Siyuan; Wei, Jun; Wang, Jingya; Sun, Huayan; Zheng, Wenting; Li, Yangguang; Sun, Yanbo; Zhao, Huiyuan; Zhang, Song; Wen, Ti; Zhou, Xinglong; Gao, Jian-Xin; Wang, Puyue; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan

    2014-05-01

    Tregs (Foxp3 + CD4 + ) are enriched in tumors to foster a tolerant microenvironment that inhibits antitumor immune response. IL-27 is reported to regulate the development and function of Tregs in vitro and in vivo; however, the effects of endogenous IL-27 on Tregs in the tumor microenvironment remain elusive. We demonstrated that in the absence of DC-derived IL-27, Tregs were decreased significantly in transplanted B16 melanoma, transplanted EL-4 lymphoma, and MCA-induced fibrosarcoma by using IL-27p28 conditional KO mice. Further studies revealed that IL-27 promoted the expression of CCL22, which is established to mediate the recruitment of peripheral Tregs into tumors. Tumor-associated DCs were identified as the major source of CCL22 in tumor sites, and IL-27 could induce CCL22 expression in an IL-27R-dependent manner. Intratumoral reconstitution of rmCCL22 or rmIL-27, but not rmIL-27p28, significantly restored the tumor infiltration of Tregs in IL-27p28 KO mice. Correlated with a decreased number of Tregs, tumor-infiltrating CD4 T cells were found to produce much more IFN-γ in IL-27p28 KO mice, which highlighted the physiological importance of Tregs in suppressing an antitumor immune response. Overall, our results identified a novel mechanism of action of IL-27 on Tregs in the context of cancers. © 2014 Society for Leukocyte Biology.

  5. A soluble inorganic pyrophosphatase from the cattle tick Rhipicephalus microplus capable of hydrolysing polyphosphates.

    PubMed

    Cruz, C S; Costa, E P; Machado, J A; Silva, J N; Romeiro, N C; Moraes, J; Silva, J R; Fonseca, R N; Vaz, I S; Logullo, C; Campos, E

    2018-04-01

    Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the cell type. In eukaryotic organisms, polyphosphates have been investigated mainly in mammalian cells, and only a few studies have addressed arthropods. Pyrophosphatases have been shown to regulate polyphosphate metabolism. However, these studies were restricted to trypanosomatids. Here we focus on the tick Rhipicephalus microplus, a haematophagous ectoparasite that is highly harmful to cattle. We produced a recombinant R. microplus pyrophosphatase (rRmPPase) with the aim of investigating its kinetic parameters using polyphosphates as substrate. Molecular docking assays of RmPPase with polyphosphates were also carried out. The kinetic and Hill coefficient parameters indicated that rRmPPase has a greater affinity, higher catalytic efficiency and increased cooperativity for sodium phosphate glass type 15 (polyP 15 ) than for sodium tripolyphosphate (polyP 3 ). Through molecular docking, we found that polyP 3 binds close to the Mg 2+ atoms in the catalytic region of the protein, participating in their coordination network, whereas polyP 15 interactions involve negatively charged phosphate groups and basic amino acid residues, such as Lys56, Arg58 and Lys193; polyP 15 has a more favourable theoretical binding affinity than polyP 3 , thus supporting the kinetic data. This study shows, for the first time in arthropods, a pyrophosphatase with polyphosphatase activity, suggesting its participation in polyphosphate metabolism. © 2017 The Royal Entomological Society.

  6. Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells

    PubMed Central

    Rac, Jürgen; Haas, Florian; Schumacher, Andrina; Middeldorp, Jaap M.; Delecluse, Henri-Jacques; Speck, Roberto F.

    2015-01-01

    The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is associated with epithelial malignancies including nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform epithelial cells in vitro where it is rapidly lost from infected primary epithelial cells or epithelial tumor cells. Long-term infection by EBV, however, can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here, we hypothesized that increased telomerase activity in epithelial cells enhances their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we generated epithelial model cell lines with increased or suppressed telomerase activity by stable ectopic expression of hTERT or of a catalytically inactive, dominant negative hTERT mutant. Infection experiments with recombinant prototypic EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able to undergo lytic replication, revealed that infection frequencies positively correlate with telomerase activity in AGS cells but also partly depend on the cellular background. AGS cells with increased telomerase activity showed increased expression mainly of latent EBV genes, suggesting that increased telomerase activity directly acts on the EBV infection of epithelial cells by facilitating latent EBV gene expression early upon virus inoculation. Thus, our results indicate that infection of epithelial cells by EBV is a very selective process involving, among others, telomerase activity and cellular background to allow for optimized host-to-host transmission via saliva. PMID:25856387

  7. Stellar kinematics and metallicities in the ultra-faint dwarf galaxy Reticulum II

    DOE PAGES

    Simon, J. D.

    2015-07-23

    With this study, we present Magellan/M2FS, Very Large Telescope/GIRAFFE, and Gemini South/GMOS spectroscopy of the newly discovered Milky Way satellite Reticulum II. Based on the spectra of 25 Ret II member stars selected from Dark Energy Survey imaging, we measure a mean heliocentric velocity ofmore » $$62.8\\pm 0.5\\;\\mathrm{km}\\;{\\rm{s}}^{-1}$$ and a velocity dispersion of $$3.3\\pm 0.7\\;\\mathrm{km}\\;{\\rm{s}}^{-1}$$. The mass-to-light ratio of Ret II within its half-light radius is $$470\\pm 210\\ {M}_{\\odot }/{L}_{\\odot }$$, demonstrating that it is a strongly dark matter-dominated system. Despite its spatial proximity to the Magellanic Clouds, the radial velocity of Ret II differs from that of the LMC and SMC by 199 and 83 $$\\mathrm{km}\\ {{\\rm{s}}}^{-1}$$, respectively, suggesting that it is not gravitationally bound to the Magellanic system. The likely member stars of Ret II span 1.3 dex in metallicity, with a dispersion of 0.28 ± 0.09 dex, and we identify several extremely metal-poor stars with $${\\rm{[Fe/H]}}\\lt -3$$. In combination with its luminosity, size, and ellipticity, these results confirm that Ret II is an ultra-faint dwarf galaxy. With a mean metallicity of $${\\rm{[Fe/H]}}=-2.65\\pm 0.07$$, Ret II matches Segue 1 as the most metal-poor galaxy known. Although Ret II is the third-closest dwarf galaxy to the Milky Way, the line-of-sight integral of the dark matter density squared is $${\\mathrm{log}}_{10}(J)=18.8\\pm 0.6\\;\\;\\mathrm{GeV}{\\;}^{2}\\;{\\mathrm{cm}}^{-5}\\;$$ within 0fdg2, indicating that the predicted gamma-ray flux from dark matter annihilation in Ret II is lower than that of several other dwarf galaxies.« less

  8. Crystal structure refinements of tetragonal (OH,F)-rich spessartine and henritermierite garnets

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

    Antao, Sytle M.; Cruickshank, Laura A.

    Cubic garnet (space group Ia\\overline 3 d) has the general formulaX 3Y 2Z 3O 12, whereX,YandZare cation sites. In the tetragonal garnet (space groupI4 1/acd), the corresponding cation sites areX1 andX2,Y, andZ1 andZ2. In both space groups only theYsite is the same. The crystal chemistry of a tetragonal (OH,F)-rich spessartine sample from Tongbei, near Yunxiao, Fujian Province, China, with composition X(Mn 2.82Fe^{2+}_{0.14}Ca 0.04) Σ3 Y{Al 1.95Fe^{3+}_{0.05}} Σ2 Z[(SiO 4) 2.61(O 4H 4) 0.28(F 4) 0.11] Σ3(Sps 94Alm 5Grs 1) was studied with single-crystal X-ray diffraction and space groupI4 1/acd. The deviation of the unit-cell parameters from cubic symmetry is smallmore » [a= 11.64463(1),c= 11.65481 (2) Å,c/a= 1.0009]. Point analyses and back-scattered electron images, obtained by electron-probe microanalysis, indicate a homogeneous composition. TheZ2 site is fully occupied, but theZ1 site contains vacancies. The occupiedZ1 andZ2 sites with Si atoms are surrounded by four O atoms, as in anhydrous cubic garnets. Pairs of split sites are O1 with F11 and O2 with O22. When theZ1 site is vacant, a larger [(O 2H 2)F 2] tetrahedron is formed by two OH and two F anions in the O22 and F11 sites, respectively. This [(O 2H 2)F 2] tetrahedron is similar to the O 4H 4tetrahedron in hydrogarnets. These results indicate ^{X}{{\\rm Mn}^ {2+}_{3}}\\,^{Y}{\\rm Al}_{2}^{Z}[({\\rm SiO}_{4})_{2}({\\rm O}_{2}{\\rm H}_{2})_{0.5}({\\rm F}_{2})_{0.5}]_{\\Sigma3} as a possible end member, which is yet unknown. The H atom that is bonded to the O22 site is not located because of the small number of OH groups. In contrast, tetragonal henritermierite, ideally ^{X}{\\rm Ca}_{3}\\,^{Y}{\\rm Mn}^{3+}_{2}\\,^{Z}[({\\rm SiO}_{4})_{2}({\\rm O}_{4}{\\rm H}_{4})_1]_{\\Sigma3}, has a vacantZ2 site that contains the O 4H 4tetrahedron. The H atom is bonded to an O3 atom [O3—H3 = 0.73 (2) Å]. Because of O2—Mn 3+—O2 Jahn–Teller elongation of the Mn 3+O 6octahedron, a weak hydrogen bond is formed to the under-bonded O2 atom. This causes a large deviation from cubic symmetry (c/a= 0.9534).« less

  9. Production enhancement and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) ≡ Natrinema altunense strain RM-G10.

    PubMed

    Mahansaria, Riddhi; Dhara, Anusua; Saha, Amit; Haldar, Saubhik; Mukherjee, Joydeep

    2018-02-01

    Application of halophiles can decrease the cost of polyhydroxyalkanoate (PHA) production or bioplastic which are an alternative to the petroleum-derived plastic. Extremely halophilic archaeon, Natrinema ajinwuensis RM-G10 accumulated 61.02±0.68% PHA of its cell dry mass at 72h in repeated batch cultures yielding 0.210±0.001gL -1 h -1 volumetric productivity after selection of the best cultivation conditions. Transmission electron microscopy showed the presence of PHA granules inside the archaeal cells. Characterization by gas chromatographic analysis, gas chromatographic- mass spectrophotometric analysis, thermogravimetric analysis, differential scanning calorimetric analysis, X-ray diffraction analysis, Fourier transform infra red spectroscopy and nuclear magnetic resonance spectroscopy revealed the polymer to be poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with 13.93mol% 3-hydroxyvalerate content and having 35.45% crystallinity, -12.3°C glass transition temperature, 143°C and 157.5°C melting temperatures and 284°C degradation temperature. This is the first report on production enhancement (on a small scale) and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) ≡ Natrinema altunense strain RM-G10 and the Natrinema genus in general. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Genetic analysis and identification of SSR markers associated with rice blast disease in a BC2F1 backcross population.

    PubMed

    Hasan, N; Rafii, M Y; Abdul Rahim, H; Nusaibah, S A; Mazlan, N; Abdullah, S

    2017-01-23

    Rice (Oryza sativa L.) blast disease is one of the most destructive rice diseases in the world. The fungal pathogen, Magnaporthe oryzae, is the causal agent of rice blast disease. Development of resistant cultivars is the most preferred method to achieve sustainable rice production. However, the effectiveness of resistant cultivars is hindered by the genetic plasticity of the pathogen genome. Therefore, information on genetic resistance and virulence stability are vital to increase our understanding of the molecular basis of blast disease resistance. The present study set out to elucidate the resistance pattern and identify potential simple sequence repeat markers linked with rice blast disease. A backcross population (BC 2 F 1 ), derived from crossing MR264 and Pongsu Seribu 2 (PS2), was developed using marker-assisted backcross breeding. Twelve microsatellite markers carrying the blast resistance gene clearly demonstrated a polymorphic pattern between both parental lines. Among these, two markers, RM206 and RM5961, located on chromosome 11 exhibited the expected 1:1 testcross ratio in the BC 2 F 1 population. The 195 BC 2 F 1 plants inoculated against M. oryzae pathotype P7.2 showed a significantly different distribution in the backcrossed generation and followed Mendelian segregation based on a single-gene model. This indicates that blast resistance in PS2 is governed by a single dominant gene, which is linked to RM206 and RM5961 on chromosome 11. The findings presented in this study could be useful for future blast resistance studies in rice breeding programs.

  11. Ethical implications of regenerative medicine in orthopedics: an empirical study with surgeons and scientists in the field.

    PubMed

    Niemansburg, Sophie L; van Delden, Johannes J M; Oner, F Cumhur; Dhert, Wouter J A; Bredenoord, Annelien L

    2014-06-01

    Regenerative medicine (RM) interventions, such as (stem) cell transplantation, scaffolds, gene transfer, and tissue engineering, are likely to change the field of orthopedics considerably. These strategies will significantly differ from treatments in current orthopedic practice, as they treat the underlying cause of disease and intervene at a biological level, preferably in an earlier stage. Whereas most of the RM interventions for orthopedics are still in the preclinical phase of research, the number of clinical studies is expected to increase rapidly in the future. The debate about the challenging scientific and ethical issues of translating these innovative interventions into (early) clinical studies is developing. However, no empirical studies that have systematically described the attitudes, opinions, and experiences of experts in the field of orthopedic RM concerning these challenges exist. The aim of this study was to identify ethical issues that experts in the area of RM for musculoskeletal disorders consider to be relevant to address so as to properly translate RM interventions into (early) clinical studies. In-depth qualitative interviews were conducted with 36 experts in the field, mainly spine surgeons and musculoskeletal scientists from The Netherlands and the United Kingdom. A topic list of open questions, based on existing literature and pilot interviews, was used to guide the interviews. Data analysis was based on the constant comparative method, which means going back and forth from the data to develop codes, concepts, and themes. Four ethical themes emerged from the interview data. First, the risks to study participants. Second, the appropriate selection of study participants. Third, setting relevant goal(s) for measuring outcome, varying from regenerating tissue to improving well-being of patients. Finally, the need for evidence-based medicine and scientific integrity, which is considered challenging in orthopedics. The overall attitude toward the development of RM was positive, especially because current surgical treatments for spine disorders lack satisfactory effectiveness. However, efforts should be taken to adequately address the ethical and scientific issues in the translation of RM interventions into clinical research. This is required to prevent unnecessary risks to study participants, to prevent exposure of future patients to useless clinical applications, as well as to prevent this young field from developing a negative reputation. Not only will the orthopedic RM field benefit from ethically and scientifically sound clinical studies, but the rise of RM also provides an opportunity to stimulate evidence-based practice in orthopedics and address hype- and profit-driven practices in orthopedics. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome.

    PubMed

    Zhang, Jian-Guo; Chen, Xiao-Juan; Liu, Fen; Zeng, Zhen-Guo; Qian, Ke-Jian

    2011-01-01

    Animal experiments showed that recruitment maneuver (RM) and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS). Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index (PaO2/FiO2), peak inspiratory pressure (PIP), Plateau pressure (Pplat), static pulmonary compliance (Cst) and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student's t test and Fisher's exact test were used to process the data. The levels of PaO2/FiO2 and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group (P<0.05). The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group (P<0.05). The EVLWI in the two groups showed downward trend after treatment (P<0.05), and the differences were signifcant at all time points (P<0.01); the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours (P<0.05 or P<0.01). Compared with pre-RM, hemodynamics changes during RM were significantly different (P<0.01); compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM (P>0.05). RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.

  13. Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages

    PubMed Central

    Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

    2018-01-01

    Objectives l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Methods Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7–13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. Results Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Conclusions Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. PMID:29686031

  14. Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

    PubMed

    Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

    2018-05-01

    l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D 2 -dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T 0 AM and T 1 AM in vitro . Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T 1 AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. © 2018 The authors.

  15. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

    PubMed

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and BCR signaling ( MTOR, FYN, CD86 ) when compared to NR. Overall, these data suggest that a perturbation at a transcriptional level in the B cell compartment persists despite stable virus control achieved through ART in HIV-infected children. Additionally, the present study demonstrates the potential utility of transcriptional evaluation of RM B cells before vaccination for identifying predictive correlates of vaccine responses in this population.

  16. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response

    PubMed Central

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27+CD21−) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27+CD21+) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses (APRIL, BTK, BLIMP1) and BCR signaling (MTOR, FYN, CD86) when compared to NR. Overall, these data suggest that a perturbation at a transcriptional level in the B cell compartment persists despite stable virus control achieved through ART in HIV-infected children. Additionally, the present study demonstrates the potential utility of transcriptional evaluation of RM B cells before vaccination for identifying predictive correlates of vaccine responses in this population. PMID:28955330

  17. Assessment of environmental risk for red mud storage facility in China: a case study in Shandong Province.

    PubMed

    Wen, Zhi-Chao; Ma, Shu-Hua; Zheng, Shi-Li; Zhang, Yi; Liang, Yan

    2016-06-01

    Red mud storage facility (RM-SF) pollution remains a serious problem in China mainly due to the RM's huge quantity, little recyclability, and high alkalinity. And, there is also a risk of dam failure because almost all RM-SFs are processed by damming. In order to address this challenge and improve the level of risk management, it is necessary to evaluate the environmental risk of RM-SFs systematically. So, this paper firstly designs a comprehensive evaluation index system with a three-level evaluation index in the terms of RM characteristics, RM-SF characteristics, ambient environment of RM-SF, the management of RM-SF, and the application aspect of RM by the analytic hierarchy process (AHP) method. Then, a case of RM-SF from a typical alumina production enterprise is studied according to this system, as is assisted by several experts from different fields when determining the weights of all indicators. The results show that the risk of selected RM-SF primarily depends on the former factors, that is, RM and RM-SF characteristics, while the contributions of the other factors are quite smaller.

  18. Stem cell research and transplantation: science leading ethics.

    PubMed

    Daar, A S; Bhatt, A; Court, E; Singer, P A

    2004-10-01

    One of the most exciting developments in the biological sciences in the past decade has been the discovery and characterization of human embryonic stem cells (ESCs). The interest to transplanters is the potential applications of stem cells in regenerative medicine (RM), which may involve tissue engineering, genetic engineering, and other techniques to repair, replace, or regenerate failing tissues and organs. There is little controversy surrounding human adult stem cells. However, human ESCs are surrounded by a number of ethical controversies, the extent of which is partly dependent on their source. Those derived from currently existing embryonic stem cell lines are less controversial than those derived from "excess" embryos from in vitro fertilization (IVF) clinics, while ESCs derived from IVF embryos specifically created for the purpose are not acceptable to many people arguing from religious and other moral perspectives. Somatic cell nuclear transfer, or therapeutic cloning, must be distinguished from reproductive cloning. It holds the most promise for regenerative medicine. ESCs can also be derived from gonadal ridges of aborted fetuses. The transplant community must strive to uphold societal values in its effort to find remedies for their ailing patients and address the perennial problem of organ shortage. Transplanters also have a responsibility to engage the public in their efforts to gain public understanding and support, and policy makers must take into account public opinion. Only in this way can we realize the great potential of stem cell research for organ transplantation.

  19. Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.

    PubMed

    Wang, Li-Qin; Yan, Xiao-Ting; Yan, Chun-Fang; Zhang, Xin-Wen; Hui, Ling-Yun; Xue, Mingzhan; Yu, Xue-Wen

    2016-01-01

    Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM). Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy. Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women. Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

  20. Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer.

    PubMed

    Sheth, Siddharth; Weiss, Jared

    2018-02-21

    Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.

  1. A compiled catalog of rotation measures of radio point sources

    NASA Astrophysics Data System (ADS)

    Xu, Jun; Han, Jin-Lin

    2014-08-01

    We compiled a catalog of Faraday rotation measures (RMs) for 4553 extragalactic radio point sources published in literature. These RMs were derived from multi-frequency polarization observations. The RM data are compared to those in the NRAO VLA Sky Survey (NVSS) RM catalog. We reveal a systematic uncertainty of about 10.0 ± 1.5 rad m-2 in the NVSS RM catalog. The Galactic foreground RM is calculated through a weighted averaging method by using the compiled RM catalog together with the NVSS RM catalog, with careful consideration of uncertainties in the RM data. The data from the catalog and the interface for the Galactic foreground RM calculations are publicly available on the webpage: http://zmtt.bao.ac.cn/RM/.

  2. Particle-in-cell simulations of electron energization in laser-driven magnetic reconnection

    DOE PAGES

    Lu, San; Lu, Quanming; Guo, Fan; ...

    2016-01-25

    Electrons can be energized during laser-driven magnetic reconnection, and the energized electrons form three super-Alfvénic electron jets in the outflow region (Lu et al 2014 New J. Phys. 16 083021). In this paper, by performing two-dimensional particle-in-cell simulations, we find that the electrons can also be significantly energized before magnetic reconnection occurs. When two plasma bubbles with toroidal magnetic fields expand and squeeze each other, the electrons in the magnetic ribbons are energized through betatron acceleration due to the enhancement of the magnetic field, and an electron temperature anisotropymore » $${T}_{{\\rm{e}}\\perp }\\gt {T}_{{\\rm{e}}| | }$$ develops. Meanwhile, some electrons are trapped and bounced repeatedly between the two expanding/approaching bubbles and get energized through a Fermi-like process. Furthermore, the energization before magnetic reconnection is more significant (or important) than that during magnetic reconnection.« less

  3. Dro1, a major QTL involved in deep rooting of rice under upland field conditions.

    PubMed

    Uga, Yusaku; Okuno, Kazutoshi; Yano, Masahiro

    2011-05-01

    Developing a deep root system is an important strategy for avoiding drought stress in rice. Using the 'basket' method, the ratio of deep rooting (RDR; the proportion of total roots that elongated through the basket bottom) was calculated to evaluate deep rooting. A new major quantitative trait locus (QTL) controlling RDR was detected on chromosome 9 by using 117 recombinant inbred lines (RILs) derived from a cross between the lowland cultivar IR64, with shallow rooting, and the upland cultivar Kinandang Patong (KP), with deep rooting. This QTL explained 66.6% of the total phenotypic variance in RDR in the RILs. A BC(2)F(3) line homozygous for the KP allele of the QTL had an RDR of 40.4%, compared with 2.6% for the homozygous IR64 allele. Fine mapping of this QTL was undertaken using eight BC(2)F(3) recombinant lines. The RDR QTL Dro1 (Deeper rooting 1) was mapped between the markers RM24393 and RM7424, which delimit a 608.4 kb interval in the reference cultivar Nipponbare. To clarify the influence of Dro1 in an upland field, the root distribution in different soil layers was quantified by means of core sampling. A line homozygous for the KP allele of Dro1 (Dro1-KP) and IR64 did not differ in root dry weight in the shallow soil layers (0-25 cm), but root dry weight of Dro1-KP in deep soil layers (25-50 cm) was significantly greater than that of IR64, suggesting that Dro1 plays a crucial role in increased deep rooting under upland field conditions.

  4. Reliability and Validity of the Load-Velocity Relationship to Predict the 1RM Back Squat.

    PubMed

    Banyard, Harry G; Nosaka, Kazunori; Haff, G Gregory

    2017-07-01

    Banyard, HG, Nosaka, K, and Haff, GG. Reliability and validity of the load-velocity relationship to predict the 1RM back squat. J Strength Cond Res 31(7): 1897-1904, 2017-This study investigated the reliability and validity of the load-velocity relationship to predict the free-weight back squat one repetition maximum (1RM). Seventeen strength-trained males performed three 1RM assessments on 3 separate days. All repetitions were performed to full depth with maximal concentric effort. Predicted 1RMs were calculated by entering the mean concentric velocity of the 1RM (V1RM) into an individualized linear regression equation, which was derived from the load-velocity relationship of 3 (20, 40, 60% of 1RM), 4 (20, 40, 60, 80% of 1RM), or 5 (20, 40, 60, 80, 90% of 1RM) incremental warm-up sets. The actual 1RM (140.3 ± 27.2 kg) was very stable between 3 trials (ICC = 0.99; SEM = 2.9 kg; CV = 2.1%; ES = 0.11). Predicted 1RM from 5 warm-up sets up to and including 90% of 1RM was the most reliable (ICC = 0.92; SEM = 8.6 kg; CV = 5.7%; ES = -0.02) and valid (r = 0.93; SEE = 10.6 kg; CV = 7.4%; ES = 0.71) of the predicted 1RM methods. However, all predicted 1RMs were significantly different (p ≤ 0.05; ES = 0.71-1.04) from the actual 1RM. Individual variation for the actual 1RM was small between trials ranging from -5.6 to 4.8% compared with the most accurate predictive method up to 90% of 1RM, which was more variable (-5.5 to 27.8%). Importantly, the V1RM (0.24 ± 0.06 m·s) was unreliable between trials (ICC = 0.42; SEM = 0.05 m·s; CV = 22.5%; ES = 0.14). The load-velocity relationship for the full depth free-weight back squat showed moderate reliability and validity but could not accurately predict 1RM, which was stable between trials. Thus, the load-velocity relationship 1RM prediction method used in this study cannot accurately modify sessional training loads because of large V1RM variability.

  5. FARADAY ROTATION STRUCTURE ON KILOPARSEC SCALES IN THE RADIO LOBES OF CENTAURUS A

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

    Feain, I. J.; Ekers, R. D.; Norris, R. P.

    2009-12-10

    We present the results of an Australia Telescope Compact Array 1.4 GHz spectropolarimetric aperture synthesis survey of 34 deg{sup 2} centered on Centaurus A-NGC 5128. A catalog of 1005 extragalactic compact radio sources in the field to a continuum flux density of 3 mJy beam{sup -1} is provided along with a table of Faraday rotation measures (RMs) and linear polarized intensities for the 28% of sources with high signal to noise in linear polarization. We use the ensemble of 281 background polarized sources as line-of-sight probes of the structure of the giant radio lobes of Centaurus A. This is themore » first time such a method has been applied to radio galaxy lobes and we explain how it differs from the conventional methods that are often complicated by depth and beam depolarization effects. Assuming a magnetic field strength in the lobes of 1.3 B {sub 1} muG, where B {sub 1} = 1 is implied by equipartition between magnetic fields and relativistic particles, the upper limit we derive on the maximum possible difference between the average RM of 121 sources behind Centaurus A and the average RM of the 160 sources along sightlines outside Centaurus A implies an upper limit on the volume-averaged thermal plasma density in the giant radio lobes of (n{sub e} ) < 5 x 10{sup -5} B {sup -1} {sub 1} cm{sup -3}. We use an RM structure function analysis and report the detection of a turbulent RM signal, with rms sigma{sub RM} = 17 rad m{sup -2} and scale size 0.{sup 0}3, associated with the southern giant lobe. We cannot verify whether this signal arises from turbulent structure throughout the lobe or only in a thin skin (or sheath) around the edge, although we favor the latter. The RM signal is modeled as possibly arising from a thin skin with a thermal plasma density equivalent to the Centaurus intragroup medium density and a coherent magnetic field that reverses its sign on a spatial scale of 20 kpc. For a thermal density of n {sub 1} 10{sup -3} cm{sup -3}, the skin magnetic field strength is 0.8 n {sup -1} {sub 1} muG.« less

  6. VizieR Online Data Catalog: Rotation measures of radio point sources (Xu+, 2014)

    NASA Astrophysics Data System (ADS)

    Xu, J.; Han, J.-L.

    2015-04-01

    We compiled a catalog of Faraday rotation measures (RMs) for 4553 extragalactic radio point sources published in literature. These RMs were derived from multi-frequency polarization observations. The RM data are compared to those in the NRAO VLA Sky Survey (NVSS) RM catalog. We reveal a systematic uncertainty of about 10.0+/-1.5rad/m2 in the NVSS RM catalog. The Galactic foreground RM is calculated through a weighted averaging method by using the compiled RM catalog together with the NVSS RM catalog, with careful consideration of uncertainties in the RM data. The data from the catalog and the interface for the Galactic foreground RM calculations are publicly available on the webpage: http://zmtt.bao.ac.cn/RM/ . (2 data files).

  7. Anomalous scaling of Δ C versus T c in the Fe-based superconductors: the $${S}_{\\pm }$$-wave pairing state model

    DOE PAGES

    Bang, Yunkyu; Stewart, G. R.

    2016-02-01

    The strong power law behavior of the specific heat jumpmore » $${\\rm{\\Delta }}C\\;$$ versus T c $$({\\rm{\\Delta }}C/{T}_{{\\rm{c}}}\\sim {T}_{{\\rm{c}}}^{\\alpha },\\alpha \\approx 2)$$, first observed by Bud'ko et al (2009 Phys. Rev. B 79 220516), has been confirmed with several families of the Fe-based superconducting compounds with various dopings. We tested a minimal two band BCS model to understand this anomalous behavior and showed that this non-BCS relation between $${\\rm{\\Delta }}C\\;$$ versus T c is a generic property of the multiband superconducting state paired by a dominant interband interaction ($${V}_{\\mathrm{inter}}\\gt {V}_{\\mathrm{intra}}$$) reflecting the relation $$\\frac{{{\\rm{\\Delta }}}_{{\\rm{h}}}}{{{\\rm{\\Delta }}}_{{\\rm{e}}}}\\sim \\sqrt{\\frac{{N}_{{\\rm{e}}}}{{N}_{{\\rm{h}}}}}$$ near T c, as in the $${S}_{\\pm }$$-wave pairing state. We also found that this $${\\rm{\\Delta }}C\\;$$ versus T c power law can continuously change from the ideal BNC scaling to a considerable deviation by a moderate variation of the impurity scattering rate $${{\\rm{\\Gamma }}}_{0}$$ (non-pair-breaking). Finally, as a result, our model provides a consistent explanation why the electron-doped Fe-based superconductors follow the ideal BNC scaling very well while the hole-doped systems often show varying degree of deviations.« less

  8. Identification of qSOR1, a major rice QTL involved in soil-surface rooting in paddy fields.

    PubMed

    Uga, Yusaku; Hanzawa, Eiko; Nagai, Shinsei; Sasaki, Kazuhiro; Yano, Masahiro; Sato, Tadashi

    2012-01-01

    Specific Indonesian lowland rice (Oryza sativa L.) cultivars elongate thick primary roots on the soil surface of paddy fields. To clarify the genetic factors controlling soil-surface rooting, we performed quantitative trait locus (QTL) analyses using 124 recombinant inbred lines (RILs) derived from a cross between Gemdjah Beton, an Indonesian lowland rice cultivar with soil-surface roots, and Sasanishiki, a Japanese lowland rice cultivar without soil-surface roots. These cultivars and the RILs were tested for soil-surface rooting in a paddy field. We identified four regions of chromosomes 3, 4, 6, and 7 that were associated with soil-surface rooting in the field. Among them, one major QTL was located on the long arm of chromosome 7. This QTL explained 32.5-53.6% of the total phenotypic variance across three field evaluations. To perform fine mapping of this QTL, we measured the basal root growth angle of crown roots at the seedling stage in seven BC(2)F(3) recombinant lines grown in small cups in a greenhouse. The QTL was mapped between markers RM21941 and RM21976, which delimit an 812-kb interval in the reference cultivar Nipponbare. We have designated this QTL qSOR1 (quantitative trait locus for SOIL SURFACE ROOTING 1).

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

    Schlaufman, Kevin C., E-mail: kcs@ucolick.or

    Of the 26 transiting exoplanet systems with measurements of the Rossiter-McLaughlin (RM) effect, eight have now been found to be significantly spin-orbit misaligned in the plane of the sky (i.e., RM misalignment angle |{lambda}| {approx}> 30{sup 0} and inconsistent with {lambda} = 0{sup 0}). Unfortunately, the RM effect does not constrain the complement misalignment angle between the orbit of the planet and the spin of its host star along the line of sight (LOS). I use a simple model of stellar rotation benchmarked with observational data to statistically identify 10 exoplanet systems from a sample of 75 for which theremore » is likely a significant degree of spin-orbit misalignment along the LOS: HAT-P-7, HAT-P-14, HAT-P-16, HD 17156, Kepler-5, Kepler-7, TrES-4, WASP-1, WASP-12, and WASP-14. All 10 systems have host stellar masses M {sub *} in the range 1.2 M {sub sun} {approx}< M {sub *} {approx}< 1.5 M {sub sun}, and the probability of this occurrence by chance is less than one in ten thousand. In addition, the planets in the candidate-misaligned systems are preferentially massive and eccentric. The coupled distribution of misalignment from the RM effect and from this analysis suggests that transiting exoplanets are more likely to be spin-orbit aligned than expected given predictions for a transiting planet population produced entirely by planet-planet scattering or Kozai cycles and tidal friction. For that reason, there are likely two populations of close-in exoplanet systems: a population of aligned systems and a population of apparently misaligned systems in which the processes that lead to misalignment or to the survival of misaligned systems operate more efficiently in systems with massive stars and planets.« less

  10. Identification and characterization of genomic regions on chromosomes 4 and 8 that control the rate of photosynthesis in rice leaves

    PubMed Central

    Adachi, Shunsuke; Tsuru, Yukiko; Nito, Naoko; Murata, Kazumasa; Yamamoto, Toshio; Ebitani, Takeshi; Ookawa, Taiichiro; Hirasawa, Tadashi

    2011-01-01

    DNA marker-assisted selection appears to be a promising strategy for improving rates of leaf photosynthesis in rice. The rate of leaf photosynthesis was significantly higher in a high-yielding indica variety, Habataki, than in the most popular Japanese variety, Koshihikari, at the full heading stage as a result of the higher level of leaf nitrogen at the same rate of application of nitrogen and the higher stomatal conductance even when the respective levels of leaf nitrogen were the same. The higher leaf nitrogen content of Habataki was caused by the greater accumulation of nitrogen by plants. The higher stomatal conductance of Habataki was caused by the higher hydraulic conductance. Using progeny populations and selected lines derived from a cross between Koshihikari and Habataki, it was possible to identify the genomic regions responsible for the rate of photosynthesis within a 2.1 Mb region between RM17459 and RM17552 and within a 1.2 Mb region between RM6999 and RM22529 on the long arm of chromosome 4 and on the short arm of chromosome 8, respectively. The designated region on chromosome 4 of Habataki was responsible for both the increase in the nitrogen content of leaves and hydraulic conductance in the plant by increasing the root surface area. The designated region on chromosome 8 of Habataki was responsible for the increase in hydraulic conductance by increasing the root hydraulic conductivity. The results suggest that it may be possible to improve photosynthesis in rice leaves by marker-assisted selection that focuses on these regions of chromosomes 4 and 8. PMID:21296764

  11. Hyperfine structure and isotope shift analysis of singly ionized titanium

    NASA Astrophysics Data System (ADS)

    Bouazza, Safa

    2013-04-01

    The even-parity low configuration system of Ti II has been considered on the basis of the experimental data found in the literature, and its fine structure has been reanalyzed by simultaneous parameterization of one- and two-body interactions for the model space (3d + 4s)3. Furthermore, the main one-electron hyperfine structure parameters for these configurations have been evaluated. For instance, for 3d24s1, a_{3{\\rm{d}}}^{01} = - {\\rm{63}}.{\\rm{2}}\\left( {{\\rm{3}}.{\\rm{1}}} \\right)\\,{\\rm{MHz}} and a_{4{\\rm{s}}}^{10} = - {\\rm{984}}.{\\rm{1}}\\left( {{\\rm{7}}.{\\rm{1}}} \\right)\\,{\\rm{MHz}} . Field shifts (FS) and specific mass shifts (SMS) of the main Ti II configurations are deduced by means of ab initio estimates combined with a small quantity of experimental isotope shift data available in the literature: FS(3d3) = -63.3 MHz, FS(3d24p1) = -49.7 MHz, FS(3d14s2) = 98.2 MHz, FS(4s24P1) = 163.4 MHz and SMS(3d3) = 1453.3 MHz, SMS(3d14s2) = -2179.7 MHz, …, referred to 3d24s1 for the pair Ti46-Ti48.

  12. Identifying the location of the OMP separatrix in DIII-D using power accounting

    DOE PAGES

    Stangeby, Peter C.; Canik, John M.; Elder, J. D.; ...

    2015-08-07

    In order to identify reliable scalings for the scrape-off layer (SOL) power width it is necessary to know the location of the separatrix in divertor tokamaks as accurately as possible, specifically its location at the outside midplane (OMP) the standard reference location. Two methods are described which use power accounting to improve the accuracy of identifying the location of the OMP separatrix. The first uses the infrared-measured deposited power profile at the outer target as the primary input, the 'more » $$P_{{\\rm SOL}}^{{\\rm exhaust}}$$ method'. The second uses the measured power input to the SOL, obtained by subtracting the power radiated from inside the separatrix from the total heating power, the ' $$P_{{\\rm SOL}}^{{\\rm input}}$$ method'. Furthermore, these two power accounting methods are illustrated with the examples of 21 H-mode DIII-D discharges. High spatial resolution Thomson scattering measured profiles of ne and Te for the main SOL near the OMP are also used as primary input to the analysis; only between-edge localized mode data are used here. The Thomson profiles are used to calculate the electron parallel conducted heat flux profiles which are then matched to the measured $$P_{{\\rm SOL}}^{{\\rm exhaust}}$$ and $$P_{{\\rm SOL}}^{{\\rm input}}$$ by adjusting the location of the OMP separatrix relative to that of the Thomson data. For these attached discharges, it is found that the values of $$R_{{\\rm sep}}^{{\\rm omp}}$$ given by the two power accounting methods agree to within ~1 mm of each other and also to within ~1 mm of the values given by the 'standard DIII-D method' described by Porter et al (1998 Phys. Plasmas 5 1410). Lastly, the shifted $$R_{{\\rm sep}}^{{\\rm omp}}$$ results in only modest changes to the values of ne and Te at the OMP separatrix relative to the 'standard' values, increasing $$n_{{\\rm e}}^{{\\rm sep}}$$ by 8% and $$T_{{\\rm e}}^{{\\rm sep}}$$ by 20%.« less

  13. The Astronomical Almanac Online - Glossary

    Science.gov Websites

    Astronomical Almanac. Δ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z $\\boldmath{\\Delta {\\rm T}}$: the difference between Terrestrial Time (TT) and Universal Time (UT): $\\Delta {\\rm T} = {\\rm TT} - {\\rm UT}1 $. $\\boldmath{\\Delta {\\rm UT1}}$ (or $\\boldmath{\\Delta {\\rm UT}}$): the value of the difference between

  14. Comparative studies of high performance swimming in sharks I. Red muscle morphometrics, vascularization and ultrastructure.

    PubMed

    Bernal, D; Sepulveda, C; Mathieu-Costello, O; Graham, J B

    2003-08-01

    Tunas (family Scombridae) and sharks in the family Lamnidae are highly convergent for features commonly related to efficient and high-performance (i.e. sustained, aerobic) swimming. High-performance swimming by fishes requires adaptations augmenting the delivery, transfer and utilization of O(2) by the red myotomal muscle (RM), which powers continuous swimming. Tuna swimming performance is enhanced by a unique anterior and centrally positioned RM (i.e. closer to the vertebral column) and by structural features (relatively small fiber diameter, high capillary density and greater myoglobin concentration) increasing O(2) flux from RM capillaries to the mitochondria. A study of the structural and biochemical features of the mako shark (Isurus oxyrinchus) RM was undertaken to enable performance-capacity comparisons of tuna and lamnid RM. Similar to tunas, mako RM is positioned centrally and more anterior in the body. Another lamnid, the salmon shark (Lamna ditropis), also has this RM distribution, as does the closely related common thresher shark (Alopias vulpinus; family Alopiidae). However, in both the leopard shark (Triakis semifasciata) and the blue shark (Prionace glauca), RM occupies the position where it is typically found in most fishes; more posterior and along the lateral edge of the body. Comparisons among sharks in this study revealed no differences in the total RM quantity (approximately 2-3% of body mass) and, irrespective of position within the body, RM scaling is isometric in all species. Sharks thus have less RM than do tunas (4-13% of body mass). Relative to published data on other shark species, mako RM appears to have a higher capillary density, a greater capillary-to-fiber ratio and a higher myoglobin concentration. However, mako RM fiber size does not differ from that reported for other shark species and the total volume of mitochondria in mako RM is similar to that reported for other sharks and for tunas. Lamnid RM properties thus suggest a higher O(2) flux capacity than in other sharks; however, lamnid RM aerobic capacity appears to be less than that of tuna RM.

  15. Comparison of muscle force production using the Smith machine and free weights for bench press and squat exercises.

    PubMed

    Cotterman, Michael L; Darby, Lynn A; Skelly, William A

    2005-02-01

    The Smith machine (SM) (vertical motion of bar on fixed path; fixed-form exercise) and free weights (FWs) (free-form path) are commonly used strength training modes. Exercisers may need to alternate between types of equipment, depending on testing, training, rehabilitation, and/or the exercisers' goals. The purposes of this study were to compare muscle force production for SM and FWs using a 1 repetition maximum (1RM) for the parallel back squat and supine bench press exercises and to predict the 1RM for one mode from 1RM on the other mode. Men (n = 16) and women (n = 16) alternately completed 1RM testing for squat and bench press using SM and FWs. Analyses of variance (type of equipment x sex) and linear regression models were calculated. A significant difference was found between bench press and squat 1RMs for each mode of equipment for all participants. The squat 1RM was greater for the SM than the FWs; conversely, the bench 1RM was greater for FWs than the SM. When sex was considered, bench 1RM for FWs was greater than SM for men and women. The squat 1RM was greater for SM than FWs for women only. The 1RM on one mode of equipment was the best predictor of 1RM for the other mode. For both sexes, the equation SM bench 1RM (in kilograms) = -6.76 + 0.95 (FW bench 1RM) can be used. For women only, SM squat 1RM (in kilograms) = 28.3 + 0.73 (FW squat 1RM). These findings provide equations for converting between SM and FW equipment for training.

  16. Growth performance, blood health, antioxidant status and immune response in red sea bream (Pagrus major) fed Aspergillus oryzae fermented rapeseed meal (RM-Koji).

    PubMed

    Dossou, Serge; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Dawood, Mahmoud A O; El Basuini, Mohammed F; Olivier, Adissin; Zaineldin, Amr I

    2018-04-01

    This study evaluated the effects of dietary substitution of fishmeal by graded levels of a blend composed of Aspergillus oryzae fermented rapeseed meal [0% (RM0), 25% (RM25), 50% (RM50), 75% (RM75) and 100% (RM100)] on growth performance, haemato-immunological responses and antioxidative status of Pagrus major (average weight 5.5 ± 0.02 g). After 56 days, growth performances were significantly improved in fish fed RM25 diet compared to control (P < 0.05). Meanwhile, up to 50% replacement of fishmeal did not affect growth performance, feed conversion efficiency, protein efficiency ratio, protein apparent digestibility, protease activity, fish somatic indices and survival compared to control. While blood hematocrit and plasma protein were significantly enhanced in groups fed RM0 and RM25 diets, most of the hematological parameters did not change through the trial except glutamic pyruvate transaminase which was significantly increased in RM75 and RM100 groups and blood cholesterol which was gradually decreased with the increasing level of the blend. Interestingly, feeding fish with RM25 and RM50 diets significantly showed enhanced lysozyme, bactericidal and peroxidase activities and fish fed the same diets showed high resistance against oxidative stress (biological antioxidant potential and reactive oxygen metabolites). Additionally, catalase activity and tolerance against low salinity seawater were higher in fish fed RM25 diet. These findings suggested that, at a moderate level (25% and 50%), substitution of fishmeal by the fermented rapeseed meal promoted growth, nutrient utilization, and exerted immune responses and anti-oxidative effects in red sea bream. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Thiazolides Elicit Anti-Viral Innate Immunity and Reduce HIV Replication.

    PubMed

    Trabattoni, Daria; Gnudi, Federica; Ibba, Salomè V; Saulle, Irma; Agostini, Simone; Masetti, Michela; Biasin, Mara; Rossignol, Jean-Francois; Clerici, Mario

    2016-06-02

    Nitazoxanide (Alinia(®), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM-5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 20 healthy donors were infected in vitro with HIV-1BaL in the presence/absence of TIZ or RM4848. HIV-1 p24 were measured at different timepoints. The immunomodulatory abilities of TZD were evaluated by the expression of type I IFN pathway genes and the production of cytokines and chemokines. TZD drastically inhibited in vitro HIV-1 replication (>87%). This was associated with the activation of innate immune responses and with the up-regulation of several interferon-stimulated genes (ISGs), including those involved in cholesterol pathway, particularly the cholesterol-25 hydroxylase (CH25H). TZD inhibition of HIV-1 replication in vitro could be due to their ability to stimulate potent and multifaceted antiviral immune responses. These data warrant the exploration of TZD as preventive/therapeutic agent in HIV infection.

  18. Meta-Cresol Purple Reference Material® (RM) for Seawater pH Measurements

    NASA Astrophysics Data System (ADS)

    Easley, R. A.; Waters, J. F.; Place, B. J.; Pratt, K. W.

    2016-02-01

    The pH of seawater is a fundamental quantity that governs the carbon dioxide - carbonate system in the world's oceans. High quality pH measurements for long-term monitoring, shipboard studies, and shorter-term biological studies (mesocosm and field experiments) can be ensured through a reference material (RM) that is compatible with existing procedures and which is traceable to primary pH measurement metrology. High-precision spectrophotometric measurements of seawater pH using an indicator dye such as meta-cresol purple (mCP) are well established. However, traceability of these measurements to the International System of Units (SI) additionally requires characterizing the spectrophotometric pH response of the dye in multiple artificial seawater buffers that themselves are benchmarked via primary pH (Harned cell) measurements at a range of pH, salinity, and temperature. NIST is currently developing such a mCP pH RM using this approach. This material will also incorporate new procedures developed at NIST for assessing the purity and homogeneity of the mCP reagent itself. The resulting mCP will provide long-term (years) stability and ease of shipment compared to artificial seawater pH buffers. These efforts will provide the oceanographic user community with a NIST issued mCP (RM), characterized as to its molar absorptivity values and acid dissociation constants (pKa), with uncertainties that comply with the Guide to the Expression of Uncertainty in Measurement (GUM).

  19. shock driven instability of a multi-phase particle-gas system

    NASA Astrophysics Data System (ADS)

    McFarland, Jacob; Black, Wolfgang; Dahal, Jeevan; Morgan, Brandon

    2015-11-01

    A computational study of a shock driven instability of a multiphse particle-gas system is presented. This instability can evolve in a similar fashion to the Richtmyer-Meshkov (RM) instability, but has addition parameters to be considered. Particle relaxation times, and density differences of the gas and particle-gas system can be adjusted to produce results which are different from the classical RM instability. We will show simulation results from the Ares code, developed at Lawrence Livermore National Laboratory, which uses a particle-in-cell approach to study the effects of the particle-gas system parameters. Mixing parameters will be presented to highlight the suppression of circulation and gas mixing by the particle phase.

  20. Synthesis, characterization and biological evaluation of ruthenium flavanol complexes against breast cancer

    NASA Astrophysics Data System (ADS)

    Singh, Ashok Kumar; Saxena, Gunjan; Sahabjada; Arshad, M.

    2017-06-01

    Four Ru(II) DMSO complexes (M1R-M4R) having substituted flavones viz. 3-Hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one (HL1), 3-Hydroxy-2-(4-nitrophenyl)-4H-chromen-4-one (HL2), 3-Hydroxy-2-(4-dimethylaminophenyl)-4H-chromen-4-one (HL3) and 3-Hydroxy-2-(4-chlorophenyl)-4H-chromen-4-one (HL4) were synthesized and characterized by elemental analysis, IR, UV-Vis, 1H NMR spectroscopies and ESI-MS. The molecular structures of the complexes were investigated by integrated spectroscopic and computational techniques (DFT). Both ligands as well as their complexes were screened for anticancer activities against breast cancer cell lines MCF-7. Cytotoxicity was assayed by MTT [3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. All ligands and their complexes exhibited significant cytotoxic potential of 5-40 μM concentration at incubation period of 24 h. The cell cytotoxicity increased significantly in a concentration-dependent manner. In this series of compounds, HL2 (IC50 17.2 μM) and its complex M2R (IC50 16 μM) induced the highest cytotoxicity.

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

    Friedman, B.; DuCharme, G.

    We present a semi-empirical scaling law for non-resonant ion–atom single charge exchange cross sections for collisions with velocities frommore » $${10}^{7}\\,{\\rm{t}}{\\rm{o}}\\,{10}^{9}\\,\\mathrm{cm}\\,{{\\rm{s}}}^{-1}$$ and ions with positive charge $$q\\lt 8$$. Non-resonant cross sections tend to have a velocity peak at collision velocities $$v\\lesssim 1\\ {\\rm{a}}{\\rm{u}}$$ with exponential decay around this peak. We construct a scaling formula for the location of this peak then choose a functional form for the cross section curve and scale it. The velocity at which the cross section peaks, v m, is proportional to the energy defect of the collision, $${\\rm{\\Delta }}E$$, which we predict with the decay approximation. The value of the cross section maximum is proportional to the charge state q, inversely proportional to the target ionization energy I T, and inversely proportional to v m. For the shape of the cross section curve, we use a function that decays exponentially asymptotically at high and low velocities. We scale this function with parameters $${v}_{{\\rm{m}}},{I}_{{\\rm{T}}},{Z}_{{\\rm{T}}},\\mathrm{and}\\ {Z}_{{\\rm{P}}}$$, where the $${Z}_{{\\rm{T}},{\\rm{P}}}$$ are the target and projectile atomic numbers. In conclusion, for the more than 100 cross section curves that we use to find the scaling rules, the scaling law predicts cross sections within a little over a factor of 2 on average.« less

  2. Tropospheric GOM at the Pic du Midi Observatory-Correcting Bias in Denuder Based Observations.

    PubMed

    Marusczak, Nicolas; Sonke, Jeroen E; Fu, Xuewu; Jiskra, Martin

    2017-01-17

    Gaseous elemental mercury (GEM, Hg) emissions are transformed to divalent reactive Hg (RM) forms throughout the troposphere and stratosphere. RM is often operationally quantified as the sum of particle bound Hg (PBM) and gaseous oxidized Hg (GOM). The measurement of GOM and PBM is challenging and under mounting criticism. Here we intercompare six months of automated GOM and PBM measurements using a Tekran (TK) KCl-coated denuder and quartz regenerable particulate filter method (GOM TK , PBM TK , and RM TK ) with RM CEM collected on cation exchange membranes (CEMs) at the high altitude Pic du Midi Observatory. We find that RM TK is systematically lower by a factor of 1.3 than RM CEM . We observe a significant relationship between GOM TK (but not PBM TK ) and Tekran flush TK blanks suggesting significant loss (36%) of labile GOM TK from the denuder or inlet. Adding the flush TK blank to RM TK results in good agreement with RM CEM (slope = 1.01, r 2 = 0.90) suggesting we can correct bias in RM TK and GOM TK . We provide a bias corrected (*) Pic du Midi data set for 2012-2014 that shows GOM* and RM* levels in dry free tropospheric air of 198 ± 57 and 229 ± 58 pg m -3 which agree well with in-flight observed RM and with model based GOM and RM estimates.

  3. Extraction of $$\\sin^2\\theta^{\\rm lept}_{\\rm eff}$$ and indirect measurement of $$m_w$$ from the 9 fb$$^{-1}$$ full run ii sample of $$\\mu^+\\mu^-$$ events at cdf

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

    Bodek, A.

    2014-09-19

    We report on the extraction ofmore » $$\\sin^2\\theta^{\\rm lept}_{\\rm eff}$$ and indirect measurement of the mass of the W boson from the forward-backward asymmetry of $$\\mu^+\\mu^-$$ events in the $Z$ boson mass region. The data sample collected by the CDF detector corresponds to the full 9 fb$$^{-1}$$ run II sample. We measure $$\\sin^2 \\theta^{\\rm lept}_{\\rm eff} = 0.2315 \\pm 0.0010$$,$$ \\sin^2 \\theta_W = 0.2233 \\pm 0.0009$$ and $$M_W ({\\rm indirect}) = 80.365 \\pm 0.047 \\;{\\rm GeV}/c^2$$, where each uncertainty includes both statistical and systematic contributions.« less

  4. On the isolation of elemental carbon (EC) for micro-molar 14C accelerator mass spectrometry: development of a hybrid reference material for 14C-EC accuracy assurance, and a critical evaluation of the thermal optical kinetic (TOK) EC isolation procedure

    NASA Astrophysics Data System (ADS)

    Currie, L. A.; Kessler, J. D.

    2005-10-01

    The primary objective of the research reported here has been the development of a hybrid reference material (RM) to serve as a test of accuracy for elemental carbon (EC) isotopic (14C) speciation measurements. Such measurements are vital for the quantitative apportionment of fossil and biomass sources of "soot" (EC), the tracer of fire that has profound effects on health, atmospheric visibility, and climate. Previous studies of 14C-EC measurement quality, carried out with NIST SRM 1649a (Urban Dust), showed a range of results, but since the "truth" was not known for this natural matrix RM, one had to rely on isotopic-chemical consistency evidence (14C in PAH, EC) of measurement validity (Currie et al., 2002). Components of the new Hybrid RM (DiesApple), however, have known 14C and EC composition, and they are nearly orthogonal (isotopically and chemically). NIST SRM 2975 (Forklift Diesel Soot) has little or no 14C, and its major compositional component is EC; SRM 1515 (Apple Leaves) has the 14C content of biomass-C, and it has little or no EC. Thus, the Hybrid RM can serve as an absolute isotopic test for the absence of EC-mimicking pyrolysis-C (char) from SRM 1515 in the EC isolate of the Hybrid RM, as well as a test for conservation of its dominant soot fraction throughout the isolation procedure.

    The secondary objective was to employ the Hybrid RM for the comparative evaluation of the thermal optical kinetic (TOK) and thermal optical transmission (TOT) methods for the isolation of EC for micro-molar carbon accelerator mass spectrometry (AMS). As part of this process, the relatively new TOK method was subjected to a critical evaluation and significant development. Key findings of our study are: (1) both methods exhibited biomass-C "leakage"; for TOT, the EC fraction isolated for AMS contained about 8% of the original biomass-C; for TOK, the refractory carbon (RC) isolated contained about 3% of the original biomass-C.; (2) the initial isothermal oxidation stage of the TOK method substantially reduced the transfer of artifact char to the RC fraction, improving isolation capabilities; (3) the Hybrid RM was not equal to the sum of its parts, with matrix interactions inducing premature loss of EC which, however, could be quantified and minimized; (4) the three-stage TOK method provided a superior capability for carbonate quantification at the sub-micromolar level, with "reagent-free" removal of carbonate-C from EC - essential for low-level EC-14C AMS.

  5. Effects of temperature on power output and contraction kinetics in the locomotor muscle of the regionally endothermic common thresher shark (Alopias vulpinus).

    PubMed

    Donley, Jeanine M; Sepulveda, Chugey A; Aalbers, Scott A; McGillivray, David G; Syme, Douglas A; Bernal, Diego

    2012-10-01

    The common thresher shark (Alopias vulpinus) is a pelagic species with medially positioned red aerobic swimming musculature (RM) and regional RM endothermy. This study tested whether the contractile characteristics of the RM are functionally similar along the length of the body and assessed how the contractile properties of the common thresher shark compare with those of other sharks. Contractile properties of the RM were examined at 8, 16 and 24 °C from anterior and posterior axial positions (0.4 and 0.6 fork length, respectively) using the work loop technique. Experiments were performed to determine whether the contractile properties of the RM are similar along the body of the common thresher shark and to document the effects of temperature on muscle power. Axial differences in contractile properties of RM were found to be small or absent. Isometric twitch kinetics of RM were ~fivefold slower than those of white muscle, with RM twitch durations of about 1 s at 24 °C and exceeding 5 s at 8 °C, a Q(10) of nearly 2.5. Power increased approximately tenfold with the 16 °C increase in temperature, while the cycle frequency for maximal power only increased from about 0.5-1.0 Hz over this temperature range. These data support the hypothesis that the RM is functionally similar along the body of the common thresher shark and corroborate previous findings from shark species both with and without medial RM. While twitch kinetics suggest the endothermic RM is not unusually temperature sensitive, measures of power suggest that the RM is not well suited to function at cool temperatures. The cycle frequency at which power is maximized appeared relatively insensitive to temperature in RM, which may reflect the relatively cooler temperature of the thresher RM compared to that observed in lamnid sharks as well as the relatively slow RM phenotype in these large fish.

  6. Greater Neural Adaptations following High- vs. Low-Load Resistance Training

    PubMed Central

    Jenkins, Nathaniel D. M.; Miramonti, Amelia A.; Hill, Ethan C.; Smith, Cory M.; Cochrane-Snyman, Kristen C.; Housh, Terry J.; Cramer, Joel T.

    2017-01-01

    We examined the neuromuscular adaptations following 3 and 6 weeks of 80 vs. 30% one repetition maximum (1RM) resistance training to failure in the leg extensors. Twenty-six men (age = 23.1 ± 4.7 years) were randomly assigned to a high- (80% 1RM; n = 13) or low-load (30% 1RM; n = 13) resistance training group and completed leg extension resistance training to failure 3 times per week for 6 weeks. Testing was completed at baseline, 3, and 6 weeks of training. During each testing session, ultrasound muscle thickness and echo intensity, 1RM strength, maximal voluntary isometric contraction (MVIC) strength, and contractile properties of the quadriceps femoris were measured. Percent voluntary activation (VA) and electromyographic (EMG) amplitude were measured during MVIC, and during randomly ordered isometric step muscle actions at 10–100% of baseline MVIC. There were similar increases in muscle thickness from Baseline to Week 3 and 6 in the 80 and 30% 1RM groups. However, both 1RM and MVIC strength increased from Baseline to Week 3 and 6 to a greater degree in the 80% than 30% 1RM group. VA during MVIC was also greater in the 80 vs. 30% 1RM group at Week 6, and only training at 80% 1RM elicited a significant increase in EMG amplitude during MVIC. The peak twitch torque to MVIC ratio was also significantly reduced in the 80%, but not 30% 1RM group, at Week 3 and 6. Finally, VA and EMG amplitude were reduced during submaximal torque production as a result of training at 80% 1RM, but not 30% 1RM. Despite eliciting similar hypertrophy, 80% 1RM improved muscle strength more than 30% 1RM, and was accompanied by increases in VA and EMG amplitude during maximal force production. Furthermore, training at 80% 1RM resulted in a decreased neural cost to produce the same relative submaximal torques after training, whereas training at 30% 1RM did not. Therefore, our data suggest that high-load training results in greater neural adaptations that may explain the disparate increases in muscle strength despite similar hypertrophy following high- and low-load training programs. PMID:28611677

  7. High cell density cultivation and recombinant protein production with Escherichia coli in a rocking-motion-type bioreactor

    PubMed Central

    2010-01-01

    Background Single-use rocking-motion-type bag bioreactors provide advantages compared to standard stirred tank bioreactors by decreased contamination risks, reduction of cleaning and sterilization time, lower investment costs, and simple and cheaper validation. Currently, they are widely used for cell cultures although their use for small and medium scale production of recombinant proteins with microbial hosts might be very attractive. However, the utilization of rocking- or wave-induced motion-type bioreactors for fast growing aerobic microbes is limited because of their lower oxygen mass transfer rate. A conventional approach to reduce the oxygen demand of a culture is the fed-batch technology. New developments, such as the BIOSTAT® CultiBag RM system pave the way for applying advanced fed-batch control strategies also in rocking-motion-type bioreactors. Alternatively, internal substrate delivery systems such as EnBase® Flo provide an opportunity for adopting simple to use fed-batch-type strategies to shaken cultures. Here, we investigate the possibilities which both strategies offer in view of high cell density cultivation of E. coli and recombinant protein production. Results Cultivation of E. coli in the BIOSTAT® CultiBag RM system in a conventional batch mode without control yielded an optical density (OD600) of 3 to 4 which is comparable to shake flasks. The culture runs into oxygen limitation. In a glucose limited fed-batch culture with an exponential feed and oxygen pulsing, the culture grew fully aerobically to an OD600 of 60 (20 g L-1 cell dry weight). By the use of an internal controlled glucose delivery system, EnBase® Flo, OD600 of 30 (10 g L-1 cell dry weight) is obtained without the demand of computer controlled external nutrient supply. EnBase® Flo also worked well in the CultiBag RM system with a recombinant E. coli RB791 strain expressing a heterologous alcohol dehydrogenase (ADH) to very high levels, indicating that the enzyme based feed supply strategy functions well for recombinant protein production also in a rocking-motion-type bioreactor. Conclusions Rocking-motion-type bioreactors may provide an interesting alternative to standard cultivation in bioreactors for cultivation of bacteria and recombinant protein production. The BIOSTAT® Cultibag RM system with the single-use sensors and advanced control system paves the way for the fed-batch technology also to rocking-motion-type bioreactors. It is possible to reach cell densities which are far above shake flasks and typical for stirred tank reactors with the improved oxygen transfer rate. For more simple applications the EnBase® Flo method offers an easy and robust solution for rocking-motion-systems which do not have such advanced control possibilities. PMID:20509968

  8. The Geography of Solar Energy.

    ERIC Educational Resources Information Center

    LaHart, David E.; Allen, Rodney F.

    1984-01-01

    After learning about two promising techniques for generating electricity--photovoltaic cells and wind energy conversion systems--secondary students analyze two maps of the United States showing solar radiation and available wind power to determine which U.S. regions have potential for these solar electric systems. (RM)

  9. Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates

    PubMed Central

    Čičin-Šain, Luka; Messaoudi, Ilhem; Park, Byung; Currier, Noreen; Planer, Shannon; Fischer, Miranda; Tackitt, Shane; Nikolich-Žugich, Dragana; Legasse, Alfred; Axthelm, Michael K.; Picker, Louis J.; Mori, Motomi; Nikolich-Žugich, Janko

    2007-01-01

    The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G1-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals. PMID:18056811

  10. Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates.

    PubMed

    Cicin-Sain, Luka; Messaoudi, Ilhem; Park, Byung; Currier, Noreen; Planer, Shannon; Fischer, Miranda; Tackitt, Shane; Nikolich-Zugich, Dragana; Legasse, Alfred; Axthelm, Michael K; Picker, Louis J; Mori, Motomi; Nikolich-Zugich, Janko

    2007-12-11

    The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G(1)-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.

  11. Experimental and ab initio structure of BrNO2

    NASA Astrophysics Data System (ADS)

    Kwabia Tchana, F.; Orphal, J.; Kleiner, I.; Rudolph, H. D.; Willner, H.; Garcia, P.; Bouba, O.; Demaison, J.; Redlich, B.

    The ν2 fundamental bands of different isotopomers of BrNO2 (79Br15N16O2, 81Br15N16O2, 79Br14N18O2 and 79Br14N16O18O) located around 13 µm were recorded using high-resolution Fourier transform infrared spectrometry. More than 8000 lines of all these isotopomers were reproduced using a Watson-type A-reduced Hamiltonian with a root-mean-square deviation of better than 7 × 10-4 cm-1 for the four isotopomers. Rotational and centrifugal distortion constants for the ν2 = 1 states as well as for the vibrational ground states of these isotopomers were determined. For the first time, an analysis of the ground-state rotational constants obtained in this study combined with the constants obtained in our previous work on the ν2 bands of 79Br14N16O2 and 81Br14N16O2 has allowed us to calculate the rm structure of nitryl bromide. The structural parameters obtained were rm(Br-N) = 2.0118(16) Å, rm(N-O) = 1.1956(12) Å and α(O-N-O) = 131.02(12) Å. A new ab initio structure of nitryl bromide calculated at the CCSD(T)/SDB-aug-cc-pVQZ level of theory is presented and was found to be in fair agreement with the experimental structure.

  12. Semi-empirical scaling for ion–atom single charge exchange cross sections in the intermediate velocity regime

    DOE PAGES

    Friedman, B.; DuCharme, G.

    2017-05-11

    We present a semi-empirical scaling law for non-resonant ion–atom single charge exchange cross sections for collisions with velocities frommore » $${10}^{7}\\,{\\rm{t}}{\\rm{o}}\\,{10}^{9}\\,\\mathrm{cm}\\,{{\\rm{s}}}^{-1}$$ and ions with positive charge $$q\\lt 8$$. Non-resonant cross sections tend to have a velocity peak at collision velocities $$v\\lesssim 1\\ {\\rm{a}}{\\rm{u}}$$ with exponential decay around this peak. We construct a scaling formula for the location of this peak then choose a functional form for the cross section curve and scale it. The velocity at which the cross section peaks, v m, is proportional to the energy defect of the collision, $${\\rm{\\Delta }}E$$, which we predict with the decay approximation. The value of the cross section maximum is proportional to the charge state q, inversely proportional to the target ionization energy I T, and inversely proportional to v m. For the shape of the cross section curve, we use a function that decays exponentially asymptotically at high and low velocities. We scale this function with parameters $${v}_{{\\rm{m}}},{I}_{{\\rm{T}}},{Z}_{{\\rm{T}}},\\mathrm{and}\\ {Z}_{{\\rm{P}}}$$, where the $${Z}_{{\\rm{T}},{\\rm{P}}}$$ are the target and projectile atomic numbers. In conclusion, for the more than 100 cross section curves that we use to find the scaling rules, the scaling law predicts cross sections within a little over a factor of 2 on average.« less

  13. Characterization and application of enterocin RM6, a bacteriocin from Enterococcus faecalis.

    PubMed

    Huang, En; Zhang, Liwen; Chung, Yoon-Kyung; Zheng, Zuoxing; Yousef, Ahmed E

    2013-01-01

    Use of bacteriocins in food preservation has received great attention in recent years. The goal of this study is to characterize enterocin RM6 from Enterococcus faecalis OSY-RM6 and investigate its efficacy against Listeria monocytogenes in cottage cheese. Enterocin RM6 was purified from E. faecalis culture supernatant using ion exchange column, multiple C18-silica cartridges, followed by reverse-phase high-performance liquid chromatography. The molecular weight of enterocin RM6 is 7145.0823 as determined by mass spectrometry (MS). Tandem mass spectrometry (MS/MS) analysis revealed that enterocin RM6 is a 70-residue cyclic peptide with a head-to-tail linkage between methionine and tryptophan residues. The peptide sequence of enterocin RM6 was further confirmed by sequencing the structural gene of the peptide. Enterocin RM6 is active against Gram-positive bacteria, including L. monocytogenes, Bacillus cereus, and methicillin-resistant Staphylococcus aureus (MRSA). Enterocin RM6 (final concentration in cottage cheese, 80 AU/mL) caused a 4-log reduction in population of L. monocytogenes inoculated in cottage cheese within 30 min of treatment. Therefore, enterocin RM6 has potential applications as a potent antimicrobial peptide against foodborne pathogens in food.

  14. Characterization and Application of Enterocin RM6, a Bacteriocin from Enterococcus faecalis

    PubMed Central

    Chung, Yoon-Kyung; Yousef, Ahmed E.

    2013-01-01

    Use of bacteriocins in food preservation has received great attention in recent years. The goal of this study is to characterize enterocin RM6 from Enterococcus faecalis OSY-RM6 and investigate its efficacy against Listeria monocytogenes in cottage cheese. Enterocin RM6 was purified from E. faecalis culture supernatant using ion exchange column, multiple C18-silica cartridges, followed by reverse-phase high-performance liquid chromatography. The molecular weight of enterocin RM6 is 7145.0823 as determined by mass spectrometry (MS). Tandem mass spectrometry (MS/MS) analysis revealed that enterocin RM6 is a 70-residue cyclic peptide with a head-to-tail linkage between methionine and tryptophan residues. The peptide sequence of enterocin RM6 was further confirmed by sequencing the structural gene of the peptide. Enterocin RM6 is active against Gram-positive bacteria, including L. monocytogenes, Bacillus cereus, and methicillin-resistant Staphylococcus aureus (MRSA). Enterocin RM6 (final concentration in cottage cheese, 80 AU/mL) caused a 4-log reduction in population of L. monocytogenes inoculated in cottage cheese within 30 min of treatment. Therefore, enterocin RM6 has potential applications as a potent antimicrobial peptide against foodborne pathogens in food. PMID:23844357

  15. Red Maca (Lepidium meyenii), a Plant from the Peruvian Highlands, Promotes Skin Wound Healing at Sea Level and at High Altitude in Adult Male Mice.

    PubMed

    Nuñez, Denisse; Olavegoya, Paola; Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia

    2017-12-01

    Nuñez, Denisse, Paola Olavegoya, Gustavo F. Gonzales, and Cynthia Gonzales-Castañeda. Red maca (Lepidium meyenii), a plant from the Peruvian highlands, promotes skin wound healing at sea level and at high altitude in adult male mice. High Alt Med Biol 18:373-383, 2017.-Wound healing consists of three simultaneous phases: inflammation, proliferation, and remodeling. Previous studies suggest that there is a delay in the healing process in high altitude, mainly due to alterations in the inflammatory phase. Maca (Lepidium meyenii) is a Peruvian plant with diverse biological properties, such as the ability to protect the skin from inflammatory lesions caused by ultraviolet radiation, as well as its antioxidant and immunomodulatory properties. The aim of this study was to determine the effect of high altitude on tissue repair and the effect of the topical administration of the spray-dried extract of red maca (RM) in tissue repair. Studies were conducted in male Balb/c mice at sea level and high altitude. Lesions were inflicted through a 10 mm-diameter excisional wound in the skin dorsal surface. Treatments consisted of either (1) spray-dried RM extract or (2) vehicle (VH). Animals wounded at high altitude had a delayed healing rate and an increased wound width compared with those at sea level. Moreover, wounding at high altitude was associated with an increase in inflammatory cells. Treatment with RM accelerated wound closure, decreased the level of epidermal hyperplasia, and decreased the number of inflammatory cells at the wound site. In conclusion, RM at high altitude generate a positive effect on wound healing, decreasing the number of neutrophils and increasing the number of macrophages in the wound healing at day 7 postwounding. This phenomenon is not observed at sea level.

  16. Selective effects of different fatigue protocols on the function of upper body muscles assessed through the force-velocity relationship.

    PubMed

    García-Ramos, Amador; Torrejón, Alejandro; Feriche, Belén; Morales-Artacho, Antonio J; Pérez-Castilla, Alejandro; Padial, Paulino; Jaric, Slobodan

    2018-02-01

    This study explored the feasibility of the force-velocity relationship (F-V) to detect the acute effects of different fatigue protocols on the selective changes of the maximal capacities of upper body muscles to produce force, velocity, and power. After determining the bench press one-repetition maximum (1RM), participants' F-V relationships were assessed during the bench press throw exercise on five separate sessions after performing one of the following fatiguing protocols: 60%1RM failure, 60%1RM non-failure, 80%1RM failure, 80%1RM non-failure, and no-fatigue. In the non-failure protocols, participants performed half the maximum number of repetitions than in their respective failure protocols. The main findings revealed that (1) all F-V relationships were highly linear (median r = 0.997 and r = 0.982 for averaged across participants and individual data, respectively), (2) the fatiguing protocols were ranked based on the magnitude of power loss as follows: 60%1RM failure > 80%1RM failure > 60%1RM non-failure > 80%1RM non-failure, while (3) the assessed maximum force and velocity outputs showed a particularly prominent reduction in the protocols based on the lowest and highest levels of fatigue (i.e., 80%1RM non-failure and 60%1RM failure), respectively. The results support the use of F-V to assess the effects of fatigue on the distinctive capacities of the muscles to produce force, velocity, and power output while performing multi-joint tasks, while the assessed maximum force and velocity capacities showed a particularly prominent reduction in the protocols based on the lowest and highest levels of fatigue (i.e., 80%1RM non-failure and 60%1RM failure), respectively.

  17. RM-CLEAN: RM spectra cleaner

    NASA Astrophysics Data System (ADS)

    Heald, George

    2017-08-01

    RM-CLEAN reads in dirty Q and U cubes, generates rmtf based on the frequencies given in an ASCII file, and cleans the RM spectra following the algorithm given by Brentjens (2007). The output cubes contain the clean model components and the CLEANed RM spectra. The input cubes must be reordered with mode=312, and the output cubes will have the same ordering and thus must be reordered after being written to disk. RM-CLEAN runs as a MIRIAD (ascl:1106.007) task and a Python wrapper is included with the code.

  18. Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer.

    PubMed

    Mo, Lijun; Chen, Qianmei; Zhang, Xinji; Shi, Xiaojun; Wei, Lili; Zheng, Dianpeng; Li, Hongwei; Gao, Jimin; Li, Jinlong; Hu, Zhiming

    2017-10-13

    ICOS + Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS + Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects. Our results demonstrated that SA-mGM-CSF vaccine was prepared successfully and tumor growth was inhibited. The tumor size in the combination group was much smaller than that in the vaccine with IgG mAb group. The portions of dendritic cells, CD8 + and CD4 + T cells in the mice blood and tumor tissues were increased after treatment with vaccine. There were more immune-suppressing Tregs infiltrated into tumor after treatment with tumor cell vaccine, and ICOS blocking could deplete the infiltrated Tregs, and T lymphocytes increased more dramatically in the combination therapy group. The concentrations of interferon-γ were increased in all vaccine group, the concentrations of Interleukin-10 and Interleukin-4 were much lower in the combination group. Our study demonstrated that ICOS blocking could deplete the tumor-infiltrated ICOS + Treg cells. Combining GM-CSF surface-modified RM-1 cell vaccine with Anti-ICOS antibody could induce better antitumor immunity than a vaccine alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Development of 1RM Prediction Equations for Bench Press in Moderately Trained Men.

    PubMed

    Macht, Jordan W; Abel, Mark G; Mullineaux, David R; Yates, James W

    2016-10-01

    Macht, JW, Abel, MG, Mullineaux, DR, and Yates, JW. Development of 1RM prediction equations for bench press in moderately trained men. J Strength Cond Res 30(10): 2901-2906, 2016-There are a variety of established 1 repetition maximum (1RM) prediction equations, however, very few prediction equations use anthropometric characteristics exclusively or in part, to estimate 1RM strength. Therefore, the purpose of this study was to develop an original 1RM prediction equation for bench press using anthropometric and performance characteristics in moderately trained male subjects. Sixty male subjects (21.2 ± 2.4 years) completed a 1RM bench press and were randomly assigned a load to complete as many repetitions as possible. In addition, body composition, upper-body anthropometric characteristics, and handgrip strength were assessed. Regression analysis was used to develop a performance-based 1RM prediction equation: 1RM = 1.20 repetition weight + 2.19 repetitions to fatigue - 0.56 biacromial width (cm) + 9.6 (R = 0.99, standard error of estimate [SEE] = 3.5 kg). Regression analysis to develop a nonperformance-based 1RM prediction equation yielded: 1RM (kg) = 0.997 cross-sectional area (CSA) (cm) + 0.401 chest circumference (cm) - 0.385%fat - 0.185 arm length (cm) + 36.7 (R = 0.81, SEE = 13.0 kg). The performance prediction equations developed in this study had high validity coefficients, minimal mean bias, and small limits of agreement. The anthropometric equations had moderately high validity coefficient but larger limits of agreement. The practical applications of this study indicate that the inclusion of anthropometric characteristics and performance variables produce a valid prediction equation for 1RM strength. In addition, the CSA of the arm uses a simple nonperformance method of estimating the lifter's 1RM. This information may be used to predict the starting load for a lifter performing a 1RM prediction protocol or a 1RM testing protocol.

  20. Strength tests for elite rowers: low- or high-repetition?

    PubMed

    Lawton, Trent W; Cronin, John B; McGuigan, Michael R

    2014-01-01

    The purpose of this project was to evaluate the utility of low- and high-repetition maximum (RM) strength tests used to assess rowers. Twenty elite heavyweight males (age 23.7 ± 4.0 years) performed four tests (5 RM, 30 RM, 60 RM and 120 RM) using leg press and seated arm pulling exercise on a dynamometer. Each test was repeated on two further occasions; 3 and 7 days from the initial trial. Per cent typical error (within-participant variation) and intraclass correlation coefficients (ICCs) were calculated using log-transformed repeated-measures data. High-repetition tests (30 RM, 60 RM and 120 RM), involving seated arm pulling exercise are not recommended to be included in an assessment battery, as they had unsatisfactory measurement precision (per cent typical error > 5% or ICC < 0.9). Conversely, low-repetition tests (5 RM) involving leg press and seated arm pulling exercises could be used to assess elite rowers (per cent typical error ≤ 5% and ICC ≥ 0.9); however, only 5 RM leg pressing met criteria (per cent typical error = 2.7%, ICC = 0.98) for research involving small samples (n = 20). In summary, low-repetition 5 RM strength testing offers greater utility as assessments of rowers, as they can be used to measure upper- and lower-body strength; however, only the leg press exercise is recommended for research involving small squads of elite rowers.

  1. Effect of 1 Repetition Maximum, 80% Repetition Maximum, and 50% Repetition Maximum Strength Exercise in Trained Individuals on Variations in Plasma Redox Biomarkers.

    PubMed

    Polotow, Tatiana G; Souza-Junior, Tácito P; Sampaio, Ricardo C; Okuyama, Alexandre R; Ganini, Douglas; Vardaris, Cristina V; Alves, Ragami C; McAnulty, Steven R; Barros, Marcelo P

    2017-09-01

    Polotow, TG, Souza-Junior, TP, Sampaio, RC, Okuyama, AR, Ganini, D, Vardaris, CV, Alves, RC, McAnulty, SR, and Barros, MP. Effect of 1RM, 80%RM, and 50%RM strength exercise in trained individuals on variations in plasma redox biomarkers. J Strength Cond Res 31(9): 2489-2497, 2017-For decades, scientists have examined the participation of oxygen/nitrogen species in anaerobic-like exercises, especially weightlifting and resistance exercises. The balance between the production of oxyradicals and antioxidant responses during anaerobic-like exercises is essential to assure adaptation to the physiological benefits of strength training and to prevent chronic harmful effects. The aim of this study is to examine the hypothesis that different weight loads (1 repetition maximum (RM), 80%RM, and 50%RM) lifted until exhaustion could impose distinct oxidative insults and elicit diverse antioxidant responses in plasma of young trained subjects. Glucose (+10%), lactate (+65%), urea (+30%), free iron (+65%), reduced/oxidized glutathione (+14 and +23%, respectively), and xanthine oxidase activity (2.2-fold) significantly increased after the 1RM test, whereas plasma antioxidant capacity dropped by 37%. When lower weight loads were applied (80%RM and 50%RM tests), heme-iron (+15 and +20%, respectively) became the prevalent pro-oxidant, although glutathione responses were only detected after 80%RM (+14%). Lactate concentration in plasma continuously increased, by 2.9-fold (80%RM) and 3.6-fold higher (50%RM test). We demonstrated that 1RM tests significantly diminish the antioxidant capacity of plasma because of iron overload, whereas 80%RM tests require higher involvement of glutathione molecules to counteract heme-iron oxidative insult. Mild redox imbalances promoted by heme-iron were found in plasma after 50%RM. Although we did not observe overall changes in muscle damage in young trained subjects, we cannot exclude the need for specific antioxidant supplementation depending on the strength protocols applied, especially for less responsive groups, such as sedentary and elderly populations.

  2. Vortex Flux Pinning in Type-Ii Superconductors

    NASA Astrophysics Data System (ADS)

    Hasan, Mohammad-Khair A. M.

    1995-01-01

    Rotational magnetization vector measurements on polycrystalline samples of rm YBa_2Cu _3O_7 (YBCO) and (Ba, K)BiO _3 at various fixed fields (H) and temperatures (T) reveal that the vortex flux density (B) in a rotational state consists of a component B_{rm R}, which rotates rigidly with sample rotation, and a B_{rm F} component, which stays at a fixed frictional angle (theta _{rm F}) relative to H. Also, B_{rm R} decreases and ultimately vanishes with increasing H, while B _{rm F} grows monotonically, implying that the vortex pinning strength have a broad distribution. This has been confirmed by the measurements on YBCO of the remanent flux density B^ {rm rm} which can be decomposed analogously into B_{R} ^{} and B_ {F}^{} at angle theta_{F}^{} relative to H. The quantity Hsin theta_{rm F},, which at equilibrium equals tau_{rm p}/mu (the average pinning torque per vortex of moment mu) decreases with increasing high H. This result and the distribution in the strength of the pinning are shown to be consistent with the collective pinning process of vortex bundling. At fixed H, tau_{rm p} decreases rapidly with increasing T, varying approximately as T^{-0.8} for both samples. For polycrystalline YBCO at 4.2 K, B_ {rm R} and B_{ rm F} are found to relax differently with time. The negative creep sign of B_ {rm R} indicates that the number of rotational vortices decreases with time, whereas B _{rm F} shows a positive creep with a negative change in theta_ {rm F}, which indicates that more frictional vortices enter the sample with a tendency of alignment in the direction of H. For grain-oriented YBCO at 4.2 K, the vortex creep measurements of B along the c-axis at different fields showed that: whenever the hysteretic changes of H are reversed in sign, the vortex flux creep (dB/dlogt) decreases very rapidly to zero, where it lingers before changing sign. At the same turning values of H, (dB/dH) also goes to zero. These properties are attributable to the reversals of the vortex motion which occur at the turning values of H and cause a reversal of frictional pinning forces.

  3. Remote Monitoring of Cardiac Implantable Electronic Devices (CIED)

    PubMed Central

    Zeitler, Emily P.; Piccini, Jonathan P.

    2016-01-01

    With increasing indications and access to cardiac implantable electronic devices (CIEDs) worldwide, the number of patients needing CIED follow up continues to rise. In parallel, the technology available for managing these devices has advanced considerably. In this setting, remote monitoring (RM) has emerged as a complement to routine in-office care. Rigorous studies, randomized and otherwise, have demonstrated advantages to CIED patient management systems which incorporates RM resulting in authoritative guidelines from relevant professional societies recommending RM for all eligible patients. In addition to clinical benefits, CIED management programs that include RM have been shown to be cost effective and associated with high patient satisfaction. Finally, RM programs hold promise for the future of CIED research in light of the massive data collected through RM databases converging with unprecedented computational capability. This review outlines the available data associated with clinical outcomes in patients managed with RM with an emphasis on randomized trials; the impact of RM on patient satisfaction, cost-effectiveness and healthcare utilization; and possible future directions for the use of RM in clinical practice and research. PMID:27134007

  4. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA) on SIV-infected Chinese rhesus macaques.

    PubMed

    Ling, Binhua; Piatak, Michael; Rogers, Linda; Johnson, Ann-Marie; Russell-Lodrigue, Kasi; Hazuda, Daria J; Lifson, Jeffrey D; Veazey, Ronald S

    2014-01-01

    Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART)-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM) treated with intensive combination antiretroviral therapy (cART) and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA). SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations. Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters. The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  5. Role of boundary conditions in helicoidal flow collimation: Consequences for the von Kármán sodium dynamo experiment.

    PubMed

    Varela, J; Brun, S; Dubrulle, B; Nore, C

    2015-12-01

    We present hydrodynamic and magnetohydrodynamic (MHD) simulations of liquid sodium flow with the PLUTO compressible MHD code to investigate influence of magnetic boundary conditions on the collimation of helicoidal motions. We use a simplified cartesian geometry to represent the flow dynamics in the vicinity of one cavity of a multiblades impeller inspired by those used in the Von-Kármán-sodium (VKS) experiment. We show that the impinging of the large-scale flow upon the impeller generates a coherent helicoidal vortex inside the blades, located at a distance from the upstream blade piloted by the incident angle of the flow. This vortex collimates any existing magnetic field lines leading to an enhancement of the radial magnetic field that is stronger for ferromagnetic than for conducting blades. The induced magnetic field modifies locally the velocity fluctuations, resulting in an enhanced helicity. This process possibly explains why dynamo action is more easily triggered in the VKS experiment when using soft iron impellers.

  6. Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial.

    PubMed

    Clement, P M; Gauler, T; Machiels, J P; Haddad, R I; Fayette, J; Licitra, L F; Tahara, M; Cohen, E E W; Cupissol, D; Grau, J J; Guigay, J; Caponigro, F; de Castro, G; de Souza Viana, L; Keilholz, U; Del Campo, J M; Cong, X J; Ehrnrooth, E; Vermorken, J B

    2016-08-01

    In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. NCT01345682 (ClinicalTrials.gov). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  7. Modified biweekly cisplatin, docetaxel plus cetuximab (TPEx) as first-line treatment for patients with recurrent/metastatic head and neck cancer.

    PubMed

    Fuchs, Hannah; Pammer, Johannes; Minichsdorfer, Christoph; Posch, Doris; Kornek, Gabriela; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2018-02-07

    Three weekly high-dose chemotherapy regimens in combination with weekly cetuximab are the treatment of choice for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN), although the majority of patients suffer from severe side effects. Thus, we investigated the efficacy and safety of an alternative, more convenient and less toxic biweekly modified cisplatin, docetaxel plus cetuximab (TPEx) regimen in this retrospective analysis. Thirty-eight patients receiving off-protocol cisplatin (50 mg/m 2 ) in combination with docetaxel (50 mg/m 2 ) plus cetuximab (500 mg/m 2 ) every other week were included. Data collection included baseline demographic, response rate (ORR) and toxicity data as well as disease control rate, overall survival (OS) and progression-free survival (PFS). The median age was 60 years, and the majority of patients suffered from oral cavity carcinomas (44.7%) followed by oropharyngeal (28.9%) and laryngeal (17.9%) carcinomas. The ORR was 50%, and four (10.5%) patients achieved a complete response, while 15 (39.5%) patients had a partial response. The OS and PFS were 10.8 months (95% CI 6.7-14.2) and 6.3 months (95% CI 5.7-6.8), respectively. The one-year survival rate was 44.7%. The therapy was well tolerated, and the most common grade 3/4 adverse events were myelosuppression (13.2%), hypomagnesaemia (23.7%) and acne-like rash (13.1%). In conclusion, modified biweekly TPEx is of comparable efficacy with conventional TPEx and represents a well-tolerated regimen in R/M SCCHN patients. Further evaluation of this protocol in prospective clinical trials is warranted.

  8. Ectopic pregnancy in women with recurrent miscarriage.

    PubMed

    Ticconi, Carlo; Capogna, Maria V; Martelli, Federica; Borelli, Barbara; Bruno, Valentina; Ergasti, Raffaella; Sorge, Roberto; Piccione, Emilio; Pietropolli, Adalgisa

    2018-05-01

    The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP). In this case-control retrospective study, the clinical cards of women followed as outpatients in the RM and low-risk pregnancy offices of the Obstetrics and Gynecology Unit at the Policlinico Tor Vergata University Hospital were carefully reviewed for the occurrence of EP. Overall, 598 women with RM and 2043 normal women without RM (controls) were included in the study. Among these women, 4974 pregnancies were analyzed, in which 2028 miscarriages occurred. The EP rate (3.51%) was significantly higher in RM than in control women (1.51%) [odds ratio = 2.31 (95% confidence interval: 2.3-2.4)]; it was particularly high in women with primary RM (5.11%). However, when EP rates were calculated not by women but by overall pregnancies, no differences could be found between RM and control women. In control women, the absence of a miscarriage in the reproductive history was associated with a lower rate of EP. Women with RM, particularly primary RM, are at increased risk of EP. This increased risk seems to be dependent on the high number of pregnancies occurring in women with RM rather than to specific characteristics of these women. © 2018 Japan Society of Obstetrics and Gynecology.

  9. Circumnuclear Star Formation and AGN Activity: Clues from Surface Brightness Radial Profile of PAHs and [{\\rm{S}}\\,{\\rm{IV}}

    NASA Astrophysics Data System (ADS)

    Esparza-Arredondo, Donaji; González-Martín, Omaira; Dultzin, Deborah; Alonso-Herrero, Almudena; Ramos Almeida, Cristina; Díaz-Santos, Tanio; García-Bernete, Ismael; Martinez-Paredes, Mariela; Rodríguez-Espinosa, Jose Miguel

    2018-06-01

    We studied the circumnuclear mid-IR emission in a sample of 19 local active galactic nuclei (AGNs) with high spatial resolution spectra using T-ReCS (Gemini) and CanariCam (GTC), together with Spitzer/IRS observations. We measured the flux and the equivalent width for the 11.3 μm PAH feature and the [S IV] line emission as a function of galactocentric distance. This allowed us to study the star formation (SF) at subkiloparsec scales from the nucleus for a large sample of nearby AGNs. The [S IV] line emission could be tracing the AGN radiation field within a few thousand times the sublimation radius (R sub), but it often peaks at distances greater than 1000 R sub. One possibility is that the SF is contributing to the [S IV] total flux. We found an 11.3 μm PAH emission deficit within the inner few tens of parsecs from the AGN. This deficit might be due to the destruction of the molecules responsible for this feature or the lack of SF at these distances. We found a sensible agreement in the expected shift of the relation of the AGN bolometric luminosity and the SF rate. This indicates that numerical models attributing the link between AGN activity and host galaxy growth to mergers are in agreement with our data, for most inner galaxy parts.

  10. Forensic data and microvariant sequence characterization of 27 Y-STR loci analyzed in four Eastern African countries.

    PubMed

    Iacovacci, Giuseppe; D'Atanasio, Eugenia; Marini, Ornella; Coppa, Alfredo; Sellitto, Daniele; Trombetta, Beniamino; Berti, Andrea; Cruciani, Fulvio

    2017-03-01

    By using the recently introduced 6-dye Yfiler ® Plus multiplex, we analyzed 462 males belonging to 20 ethnic groups from four eastern African countries (Eritrea, Ethiopia, Djibouti and Kenya). Through a Y-STR sequence analysis, combined with 62 SNP-based haplogroup information, we were able to classify observed microvariant alleles at four Y-STR loci as either monophyletic (DYF387S1 and DYS458) or recurrent (DYS449 and DYS627). We found evidence of non-allelic gene conversion among paralogous STRs of the two-copy locus DYF387S1. Twenty-two diallelic and triallelic patterns observed at 13 different loci were found to be significantly over-represented (p<10 -6 ) among profiles obtained from cell lines compared to those from blood and saliva. Most of the diallelic/triallelic patterns from cell lines involved recurrent mutations at rapidly mutating loci (RM Y-STRs) included in the multiplex (p<10 -2 ). At haplotype level, intra-population diversity indices were found to be among the lowest so far reported for the Yfiler ® Plus, while statistically significant differences among countries and ethnic groups were detected when considering haplotype frequencies alone (F ST ) or by using molecular distances among haplotypes (Φ ST ). The strong population subdivision observed is probably the consequence of the patrilineal social organization of most eastern African ethnic groups, and suggests caution in the use of country-based haplotype frequency distributions for forensic inferences in this region. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. The influence of isometric preload on power expressed during bench press in strength-trained men.

    PubMed

    Bartolomei, Sandro; Fukuda, David H; Hoffman, Jay R; Stout, Jeffrey R; Merni, Franco

    2017-03-01

    The purpose of this study was to compare the power expressed during the bench press exercise in resistance-trained men following different pre-activation conditions. Twenty-two trained men (age 24.1 ± 1.7 years, height 178.6 ± 6.1 cm, body mass 81.1 ± 10.6 kg) completed a maximal effort bench press (1-RM) test (100.0 kg ± 8.1 kg). In a subsequent assessment, each participant performed concentric bench press movements with loads of 20%, 30%, 40% and 50% of their 1-RM preceded by either a concentric contraction (CC), a low isometric preload (LIP; 70% 1-RM) or a high isometric preload (HIP; 100% 1-RM) conditions. All movements were performed in a Smith machine with a settable quick-release device. Participants performed all three conditions in randomized fashion. Results indicated that power outputs during the bench press exercise following HIP were significantly (p < 0.05) greater than CC at 20% 1-RM (+9%), 30% 1-RM (+16%) and 40% 1-RM (+14%), and LIP at 20% 1-RM (+4%), 30% 1-RM (+20%) and 40% 1-RM (+15%). No differences were found between conditions at 50% 1-RM. Area under the force-power curve with HIP was greater (p < 0.05) than with CC and LIP. In conclusion, results of this study indicate that the use of a HIP (100% 1-RM) in trained participants results in significantly greater power output during the concentric phase of a multi-joint exercise when compared to standard concentric movement.

  12. Structural and biochemical insights into the substrate-binding mechanism of a novel glycoside hydrolase family 134 β-mannanase.

    PubMed

    You, Xin; Qin, Zhen; Li, Yan-Xiao; Yan, Qiao-Juan; Li, Bin; Jiang, Zheng-Qiang

    2018-06-01

    Mannan is one of the major constituent groups of hemicellulose, which is a renewable resource from higher plants. β-Mannanases are enzymes capable of degrading lignocellulosic biomass. Here, an endo-β-mannanase from Rhizopus microsporus (RmMan134A) was cloned and expressed. The recombinant RmMan134A showed maximal activity at pH 5.0 and 50 °C, and exhibited high specific activity towards locust bean gum (2337 U/mg). To gain insight into the substrate-binding mechanism of RmMan134A, four complex structures (RmMan134A-M3, RmMan134A-M4, RmMan134A-M5 and RmMan134A-M6) were further solved. These structures showed that there were at least seven subsites (-3 to +4) in the catalytic groove of RmMan134A. Mannose in the -1 subsite hydrogen bonded with His113 and Tyr131, revealing a unique conformation. Lys48 and Val159 formed steric hindrance, which impedes to bond with galactose branches. In addition, the various binding modes of RmMan134A-M5 indicated that subsites -2 to +2 are indispensable during the hydrolytic process. The structure of RmMan134A-M4 showed that mannotetrose only binds at subsites +1 to +4, and RmMan134A could therefore not hydrolyze mannan oligosaccharides with degree of polymerization ≤4. Through rational design, the specific activity and optimal conditions of RmMan134A were significantly improved. The purpose of this paper is to investigate the structure and function of fungal GH family 134 β-1,4-mannanases, and substrate-binding mechanism of GH family 134 members. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. The Postconditioning Effects Of Diazoxide in the Brain Following Hemorrhagic Shock and Cerebral Hypoperfusion

    DTIC Science & Technology

    2009-10-13

    ERK to promote cell survival. RISK can be activated by insulin, urocortin, atorvastatin , adenosine, bradykinin, opioid agonists, volatile...Bell, R.M. and D.M. Yellon, Atorvastatin , administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by

  14. A New Soluble Gelatin Sponge for Transcatheter Hepatic Arterial Embolization

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

    Takasaka, Isao; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp

    2010-12-15

    To prepare a soluble gelatin sponge (GS) and to explore the GS particles (GSPs) that inhibit development of collateral pathways when transcatheter hepatic arterial embolization is performed. The approval of the Institutional Committee on Research Animal Care of our institution was obtained. By means of 50 and 100 kDa of regenerative medicine-gelatin (RM-G), RM-G sponges were prepared by freeze-drying and heating to temperatures of 110-150{sup o}C for cross-linkage. The soluble times of RM-GSPs were measured in vitro. Eight swine for transcatheter hepatic arterial embolization were assigned into two groups: six received 135{sup o}C/50RM-GSPs, 125{sup o}C/100RM-GSPs, and 138{sup o}C/50RM-GSPs, with solublemore » time of 48 h or more in vitro; two swine received Gelpart GSPs (G-GSPs) with insoluble time of 14 days as a control. Transarterial chemoembolization was performed on two branches of the hepatic artery per swine. RM-GSPs heated at temperatures of 110-138{sup o}C were soluble. Mean soluble times of the RM-GSPs increased with higher temperature. Hepatic branches embolized with G-GSP remained occluded after 6 days, and development of collateral pathways was observed after 3 days. Hepatic branches embolized with 135{sup o}C/50RM-GSP and 125{sup o}C/100RM-GSP remained occluded for 4 h, and recanalization was observed after 1 day. Hepatic branches embolized with 138{sup o}C/50RM-GS remained occluded for 1 day, and recanalization was observed after 2 days with no development of collateral pathways. In RM-GSs with various soluble times that were prepared by modulating the heating temperature, 138{sup o}C/50RM-GSP was the soluble GSP with the longest occlusion time without inducing development of collateral pathways.« less

  15. Optically dark excitonic states mediated exciton and biexciton valley dynamics in monolayer WSe2.

    PubMed

    Zhang, Minghua; Fu, Jiyong; Dias, A C; Qu, Fanyao

    2018-05-18

    We present a theory to address the photoluminescence (PL) intensity and valley polarization (VP) dynamics in monolayer WSe$_2$, under the impact of excitonic dark states of both excitons and biexcitons. We find that the PL intensity of all excitonic channels including intravalley exciton (X$_{\\rm b}$), intravalley biexciton (XX$_{\\rm k,k}$) and intervalley biexciton (XX$_{\\rm k,k^\\prime}$) in particular for the {XX$_{\\rm k,k}$} PL is enhanced by laser excitation fluence. In addition, our results indicate the anomalous temperature dependence of PL, i.e., increasing with temperature, as a result of favored phonon assisted dark-to-bright scatterings at high temperatures. Moreover, we observe that the PL is almost immune to intervalley scatterings, which trigger the exchange of excitonic states between the two valleys. As far as the valley polarization is concerned, we find that the VP of X$_{\\rm b}$ shrinks as temperature increases, exhibiting opposite temperature response to PL, while the intravalley XX$_{\\rm k,k}$ VP is found almost independent of temperature. In contrast to both X$_{\\rm b}$ and XX$_{\\rm k,k}$, the intervalley XX$_{\\rm k,k^\\prime}$ VP identically vanishes, because of equal populations of excitons in the $K$ and $K^\\prime$ valleys bounded to form intervalley biexcitons. Notably, it is found that the X$_{\\rm b}$ VP much more strongly depends on bright-dark scattering than that of {XX$_{\\rm k,k}$}, making dark state act as a robust reservoir for valley polarization against intervalley scatterings for X$_{\\rm b}$ at strong bright-dark scatterings, but not for XX$_{\\rm k,k}$. Dark excitonic states enabled enhancement of VP benefits quantum technology for information processing based on the valley degree of freedom in valleytronic devices. Furthermore, the VP has strong dependence on intervalley scattering but maintains essentially constant with excitation fluence. Finally, the time evolution of PL and VP, depending on temperature and excitation fluence, is discussed. © 2018 IOP Publishing Ltd.

  16. Inhibition of seedling survival under Rhododendron maximum (Ericaceae): could allelopathy be a cause?

    PubMed

    Nilsen, E T; Walker, J F; Miller, O K; Semones, S W; Lei, T T; Clinton, B D

    1999-11-01

    In the southern Appalachian mountains a subcanopy species, Rhododendron maximum, inhibits the establishment and survival of canopy tree seedlings. One of the mechanisms by which seedlings could be inhibited is an allelopathic effect of decomposing litter or leachate from the canopy of R. maximum (R.m.) on seed germination, root elongation, or mycorrhizal colonization. The potential for allelopathy by R.m. was tested with two bioassay species (lettuce and cress), with seeds from four native tree species, and with three ectomycorrhizal fungi. Inhibitory influences of throughfall, fresh litter, and decomposed litter (organic layer) from forest with R.m. (+R.m. sites) were compared to similar extractions made from forest without R.m. (-R.m. sites). Throughfall and leachates of the organic layer from both +R.m. and -R.m. sites stimulated germination of the bioassay species above that of the distilled water control, to a similar extent. There was an inhibitory effect of leachates of litter from +R.m. sites on seed germination and root elongation rate of both bioassay species compared with that of litter from -R.m. sites. Native tree seed stratified in forest floor material from both forest types had a slightly higher seed germination rate compared with the control. A 2-yr study of seed germination and seedling mortality of two tree species, Quercus rubra and Prunus serotina, in field plots showed no significant influence of litter or organic layer from either forest type. Incorporating R.m. leaf material into the growth medium in vitro depressed growth of one ectomycorrhizal species but did not affect two other species. Leaf material from other deciduous tree species depressed ectomycorrhizal growth to a similar or greater extent as leaf material from R.m. In conclusion, R.m. litter can have an allelopathic effect on seed germination and root elongation of bioassay species as well as some ectomycorrhizal species. However, this allelopathic affect is not manifest in field sites and is not likely to be an important cause for the inhibition of seedling survival within thickets of R.m.

  17. Microwave Dissipation due to Vortices in High - Superconductors

    NASA Astrophysics Data System (ADS)

    Anand, Niraj

    1995-01-01

    Using meander line resonant structures, we perform highly sensitive measurements of the changes in surface resistance Delta R_{s} of Y{rm Ba}_{2} {rm Cu}_{3}{rm O }_{rm 7-x} thin films in order to probe vortex dynamics as a function of temperature, applied dc magnetic field (H), and angle (theta) of the applied field relative to the ab planes. In our experiments, we observe that the component of the magnetic field normal to the ab planes produces substantially more dissipation than the component parallel to the ab planes. By using an extension of the London theory to anisotropic superconductors, we can calculate the internal flux densities parallel (B_{ab}) and perpendicular (B_{c}) to the ab planes inside a superconductor for an arbitrary field orientation relative to the ab planes. For low fields, we can define a weight (delta) of the relative contribution to dissipation from B _{ab} relative to that from B _{c}. This allows us to calculate an "effective internal flux density and hence obtain the total dissipation. Using the results from this theory, we obtain excellent quantitative agreement with our measurements of Delta R_{s} vs. theta. This is only possible if we take into account both the anisotropic screening and the anisotropic response of the material. We have also measured the magnetic field dependence of dissipation for fields applied at shallow angles from the ab planes. Here we observe two regions of markedly different dissipation separated by a temperature dependent crossover field H_{cr}(T). For H>H_{cr}(T) we observe a strong linear dependence of Delta R_ {s} vs. H. For HH_{cr}(T)]. . We have also measured thermally activated motion of field-induced vortices in a uniform lattice of pinning sites produced by selectively removing superconducting island from a 1000times1000 array of proximity-effect Josephson junctions. Such a defect array can serve as a "model" system for studying pinning in granular materials such as the high-T_ {c} superconductors.

  18. Characterization and Potential Environmental Risks of Leachate from Shredded Rubber Mulches

    PubMed Central

    Kanematsu, Masakazu; Hayashi, Ai; Denison, Michael S.; Young, Thomas M.

    2009-01-01

    In order to determine whether shredded rubber mulches (RM) posed water quality risks when used in stormwater best management practices (BMPs) such as bioretention basins, batch leaching tests were conducted to identify and quantify constituents in leachates from RM such as metal ions, nutrients, total organic carbon (TOC), and aryl hydrocarbon receptor (AhR) activity (determined by the chemically activated luciferase gene expression (CALUX) bioassay) at varied temperature and initial pH values. The results indicate that aqueous extracts of RM contain high concentrations of zinc (Zn) compared with wood mulches (WM), and its concentration increased at lower pH and higher temperature. Although methanol extracts of RM displayed high AhR activity, none of the aqueous extracts of RM had significant activity. Hence, while unknown constituents that have significant AhR activity are present in RM, they appear to be not measurably extracted by water under environmental conditions relevant for stormwater (5 < pH < 9, 10 < T < 40°C). Our results suggests that organic constituents in water extracts of RM which have AhR activity may not be of significant concern while leaching of Zn from RM appears to be a potentially larger water quality issue for RM. PMID:19450864

  19. Comparative cost-effectiveness of HPV vaccines in the prevention of cervical cancer in Malaysia.

    PubMed

    Ezat, Sharifa W P; Aljunid, Syed

    2010-01-01

    Cervical cancer (CC) had the second highest incidence of female cancers in Malaysia in 2003-2006. Prevention is possible by both Pap smear screening and HPV vaccination with either the bivalent vaccine (BV) or the quadrivalent vaccine (QV). In the present study, cost effectiveness options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination). A scenario based sensitivity analysis was conducted using screening population coverages (40-80%) and costs of vaccines (RM 100-200/dose) were calculated. This was an economic burden, cross sectional study in 2006-2009 of respondents interviewed from six public Gynecology-Oncology hospitals. Methods included expert panel discussions to estimate treatment costs of CC, genital warts and vulva/vagina cancers by severity and direct interviews with respondents using costing and SF-36 quality of life questionnaires. A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear in the base case was RM 1,215 and RM 1,100 at increased screening coverage. With QV only, in base case it was RM 15,662 and RM 24,203 when the vaccination price was increased. With BV only, the respective figures were RM 1,359,057 and RM 2,530,018. For QV combined strategy cost/QALY in the base case it was RM 4,937, reducing to RM 3,395 in the best case and rising to RM 7,992 in the worst case scenario. With the BV combined strategy, these three cost/QALYs were RM 6,624, RM 4,033 and RM 10,543. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher was highly cost effective at RM 946.74 per QALYs saved but this was preceded by best case combined strategy with QV at RM 515.29 per QALYs saved. QV is more cost effective than BV. The QV combined strategy had a higher CE than any method including Pap smear screening at high population coverage.

  20. Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells

    PubMed Central

    2010-01-01

    Background Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). Methods We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells. PMID:20423495

  1. Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

    PubMed

    Wan, Jennifer Man-Fan; Sit, Wai-Hung; Yang, Xiaotong; Jiang, Pingping; Wong, Leo Lap-Yan

    2010-04-27

    Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

  2. Repeated hematopoietic stem and progenitor cell mobilization without depletion of the bone marrow stem and progenitor cell pool in mice after repeated administration of recombinant murine G-CSF.

    PubMed

    de Kruijf, Evert-Jan F M; van Pel, Melissa; Hagoort, Henny; Kruysdijk, Donnée; Molineux, Graham; Willemze, Roel; Fibbe, Willem E

    2007-05-01

    Administration of recombinant-human G-CSF (rhG-CSF) is highly efficient in mobilizing hematopoietic stem and progenitor cells (HSC/HPC) from the bone marrow (BM) toward the peripheral blood. This study was designed to investigate whether repeated G-CSF-induced HSC/HPC mobilization in mice could lead to a depletion of the bone marrow HSC/HPC pool with subsequent loss of mobilizing capacity. To test this hypothesis Balb/c mice were treated with a maximum of 12 repeated 5-day cycles of either 10 microg rhG-CSF/day or 0.25 microg rmG-CSF/day. Repeated administration of rhG-CSF lead to strong inhibition of HSC/HPC mobilization toward the peripheral blood and spleen after >4 cycles because of the induction of anti-rhG-CSF antibodies. In contrast, after repeated administration of rmG-CSF, HSC/HPC mobilizing capacity remained intact for up to 12 cycles. The number of CFU-GM per femur did not significantly change for up to 12 cycles. We conclude that repeated administration of G-CSF does not lead to depletion of the bone marrow HSC/HPC pool.

  3. Architectural assessment of rhesus macaque pelvic floor muscles: comparison for use as a human model.

    PubMed

    Stewart, Amanda M; Cook, Mark S; Esparza, Mary C; Slayden, Ov D; Alperin, Marianna

    2017-10-01

    Animal models are essential to further our understanding of the independent and combined function of human pelvic floor muscles (PFMs), as direct studies in women are limited. To assure suitability of the rhesus macaque (RM), we compared RM and human PFM architecture, the strongest predictor of muscle function. We hypothesized that relative to other models, RM best resembles human PFM. Major architectural parameters of cadaveric human coccygeus, iliococcygeus, and pubovisceralis (pubococcygeus + puborectalis) and corresponding RM coccygeus, iliocaudalis, and pubovisceralis (pubovaginalis + pubocaudalis) were compared using 1- and 2-way analysis of variance (ANOVA) with post hoc testing. Architectural difference index (ADI), a combined measure of functionally relevant structural parameters predictive of length-tension, force-generation, and excursional muscle properties was used to compare PFMs across RM, rabbit, rat, and mouse. RM and human PFMs were similar with respect to architecture. However, the magnitude of similarity varied between individual muscles, with the architecture of the most distinct RM PFM, iliocaudalis, being well suited for quadrupedal locomotion. Except for the pubovaginalis, RM PFMs inserted onto caudal vertebrae, analogous to all tailed animals. Comparison of the PFM complex architecture across species revealed the lowest, thus closest to human, ADI for RM (1.9), followed by rat (2.0), mouse (2.6), and rabbit (4.7). Overall, RM provides the closest architectural representation of human PFM complex among species examined; however, differences between individual PFMs should be taken into consideration. As RM is closely followed by rat with respect to PFM similarity with humans, this less-sentient and substantially cheaper model is a good alternative for PFM studies.

  4. Rehabilitation Medicine Educational Experiences: A Retrospective Study of Exposure to RM.

    ERIC Educational Resources Information Center

    Dobmeyer, Thomas W.

    1979-01-01

    A study was conducted to determine: the effect of rehabilitation medicine (RM) educational experiences during medical school on physicians' awareness of RM; attitude toward RM; the management of long-term care; and the tendency to seek expert consultation and patient referral when necessary. (Author/MH)

  5. 77 FR 2242 - Radio Broadcasting Services; Ehrenberg, First Mesa, Kachina Village, Wickenburg, and Williams, AZ...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 08-85; RM-11427, RM-11517, RM-11518, RM-11519; DA 11- 2059] Radio Broadcasting Services; Ehrenberg, First Mesa, Kachina Village, Wickenburg, and Williams, AZ, and Needles, CA AGENCY: Federal Communications Commission. ACTION: Proposed...

  6. Velocity-resolved [{\\rm{C}}\\,{\\rm{II}}] Emission from Cold Diffuse Clouds in the Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Goldsmith, Paul F.; Pineda, Jorge L.; Neufeld, David A.; Wolfire, Mark G.; Risacher, Christophe; Simon, Robert

    2018-04-01

    We have combined emission from the 158 μm fine structure transition of C+ observed with the GREAT and upGREAT instruments on SOFIA with 21 cm absorption spectra and visual extinction to characterize the diffuse interstellar clouds found along the lines of sight. The weak [C II] emission is consistent in velocity and line width with the strongest H I component produced by the cold neutral medium. The H I column density and kinetic temperature are known from the 21 cm data and, assuming a fractional abundance of ionized carbon, we calculate the volume density and thermal pressure of each source, which vary considerably, with 27 {cm}}-3≤slant n({{{H}}}0) ≤slant 210 cm‑3 considering only the atomic hydrogen along the lines of sight to be responsible for the C+, while 13 {cm}}-3≤slant n({{{H}}}0+{{{H}}}2)≤slant 190 cm‑3 including the hydrogen in both forms. The thermal pressure varies widely with 1970 cm‑3 K ≤slant {P}th}/k≤slant 10,440 cm‑3 K for H0 alone and 750 cm‑3 K ≤ P th/k ≤ 9360 cm‑3 K including both H0 and H2. The molecular hydrogen fraction varies between 0.10 and 0.67. Photoelectric heating is the dominant heating source, supplemented by a moderately enhanced cosmic ray ionization rate, constrained by the relatively low 45 K to 73 K gas temperatures of the clouds. The resulting thermal balance for the two lower-density clouds is satisfactory, but for the two higher-density clouds, the combined heating rate is insufficient to balance the observed C+ cooling.

  7. Development and characterization of japonica rice lines carrying the brown planthopper-resistance genes BPH12 and BPH6.

    PubMed

    Qiu, Yongfu; Guo, Jianping; Jing, Shengli; Zhu, Lili; He, Guangcun

    2012-02-01

    The brown planthopper (Nilaparvata lugens Stål; BPH) has become a severe constraint on rice production. Identification and pyramiding BPH-resistance genes is an economical and effective solution to increase the resistance level of rice varieties. All the BPH-resistance genes identified to date have been from indica rice or wild species. The BPH12 gene in the indica rice accession B14 is derived from the wild species Oryza latifolia. Using an F(2) population from a cross between the indica cultivar 93-11 and B14, we mapped the BPH12 gene to a 1.9-cM region on chromosome 4, flanked by the markers RM16459 and RM1305. In this population, BPH12 appeared to be partially dominant and explained 73.8% of the phenotypic variance in BPH resistance. A near-isogenic line (NIL) containing the BPH12 locus in the background of the susceptible japonica variety Nipponbare was developed and crossed with a NIL carrying BPH6 to generate a pyramid line (PYL) with both genes. BPH insects showed significant differences in non-preference in comparisons between the lines harboring resistance genes (NILs and PYL) and Nipponbare. BPH growth and development were inhibited and survival rates were lower on the NIL-BPH12 and NIL-BPH6 plants compared to the recurrent parent Nipponbare. PYL-BPH6 + BPH12 exhibited 46.4, 26.8 and 72.1% reductions in population growth rates (PGR) compared to NIL-BPH12, NIL-BPH6 and Nipponbare, respectively. Furthermore, insect survival rates were the lowest on the PYL-BPH6 + BPH12 plants. These results demonstrated that pyramiding different BPH-resistance genes resulted in stronger antixenotic and antibiotic effects on the BPH insects. This gene pyramiding strategy should be of great benefit for the breeding of BPH-resistant japonica rice varieties.

  8. Analysis and application of a velocity command motor as a reaction mass actuator

    NASA Technical Reports Server (NTRS)

    Sulla, Jeffrey L.; Juang, Jer-Nan; Horta, Lucas G.

    1990-01-01

    A commercially available linear stepper motor is applied as a reaction mass (RM) actuator. With the actuator operating in the (RM) relative-velocity command mode, open-loop and closed-loop testing is performed to determine operational limits. With the actuator mounted on a simple beam structure, root strain, RM acceleration, or beam acceleration is used in the feedback loop to augment the structural damping. The RM relative position is also used as feedback to ensure that the RM remains centered.

  9. TCR-pMHC encounter differentially regulates transcriptomes of tissue-resident CD8 T cells.

    PubMed

    Yoshizawa, Akihiro; Bi, Kevin; Keskin, Derin B; Zhang, Guanglan; Reinhold, Bruce; Reinherz, Ellis L

    2018-01-01

    To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (T R ) differentiation, polyclonal responses were compared against NP 366-374 /D b and PA 224-233 /D b , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103 + and CD103 - CD8 T R generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherens junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGF-β signaling pathways and memory signatures among PA 224-233 /D b T cells consistent with T resident memory (T RM ) status. In contrast, NP 366-374 /D b T cells exhibit enrichment of effector signatures, upregulating pro-inflammatory mediators even among T RM . While NP 366-374 /D b T cells manifest transcripts linked to canonical exhaustion pathways, PA 224-233 /D b T cells exploit P2rx7 purinoreceptor attenuation. The NP 366-374 /D b CD103 + subset expresses the antimicrobial lactotransferrin whereas PA 224-233 /D b CD103 + utilizes pore-forming mpeg-1, with <22% of genes correspondingly upregulated in CD103 + (or CD103 - ) subsets of both specificities. Thus, TCR-pMHC interactions among T R and antigen presenting cells in a tissue milieu strongly impact CD8 T cell biology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Integrated Systems of Manufacture (Robotics) Technology Working Group Report (IDA/OSD R&M (Institute for Defense Analyses/Office of the Secretary of Defense Reliability and Maintainability) Study)

    DTIC Science & Technology

    1983-11-01

    INSTRUMENTATION ;(U) FORKLIFT VEHICLES ;(U) EXPERIMENTAL DATA IDENTIFIERS: OBJECTIVE: (U) SUPPORT INHOUSE RESEARCH FOR- ACQUISITION AND ANALYSIS OF...ROBOTIC RECONNAISSANCE VEHICLE DEMONSTRATOR WITH TERRAIN ANALYSIS . THIS WORK WILL SPECIFY THE BASE LINE HARDWARE, SOFTWARE, DATA BASE, AND SYSTEM...THE DATA ANALYSIS . THIS IS ALSO TRUE OF INFLIGMT DATA THAT THE PILOT IS REQUIRED TO ANALYZE. THIS RESEARCH IS CONCERNED WITH THE REPORT NO. CX7419

  11. Species Profiles. Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (Mid-Atlantic). Spot

    DTIC Science & Technology

    1989-02-01

    lateral line scales, 72-77; Norfolk spot, golden croaker (during gill rakers short, 8 to 12 on the spawning season ), croaker, goody, upper limb and 20 to... pteropods , larval Sinc lage-cal motaltie of pelecypods, and cyclopoid copepods juveniles are not observed in the elecypodst and cyc)opo copepodsnursry...and R.S. Birdsong. 1985. Beaufort, N.C. Seasonal occurrence of larval and juvenile fishes in a Virginia Engle, D.W., and R.M. Thuotte. 1976

  12. Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.

    PubMed

    Li, S; Ballou, L R; Morham, S G; Blatteis, C M

    2001-08-10

    Various lines of evidence have implicated cyclooxygenase (COX)-2 as a modulator of the fever induced by the exogenous pyrogen lipopolysaccharide (LPS). Thus, treatment with specific inhibitors of COX-2 suppresses the febrile response without affecting basal body (core) temperature (T(c)). Furthermore, COX-2 gene-ablated mice are unable to develop a febrile response to intraperitoneal (i.p.) LPS, whereas their COX-1-deficient counterparts produce fevers not different from their wild-type (WT) controls. To extend the apparently critical role of COX-2 for LPS-induced fevers to fevers produced by endogenous pyrogens, we studied the thermal responses of COX-1- and COX-2 congenitally deficient mice to i.p. and intracerebroventricular (i.c.v.) injections of recombinant murine (rm) interleukin (IL)-1beta. We also assessed the effects of one selective COX-1 inhibitor, SC-560, and two selective COX-2 inhibitors, nimesulide (NIM) and dimethylfuranone (DFU), on the febrile responses of WT and COX-1(-/-) mice to LPS and rmIL-1beta, i.p. Finally, we verified the integrity of the animals' responses to PGE2, i.c.v. I.p. and i.c.v. rmIL-1beta induced similar fevers in WT and COX-1 knockout mice, but provoked no rise in the T(c)s of COX-2 null mutants. The fever produced in WT mice by i.p. LPS was not affected by SC-560, but it was attenuated and abolished by NIM and DFU, respectively, while that caused by i.p. rmIL-1beta was converted into a T(c) fall by DFU. There were no differences in the responses to i.c.v. PGE2 among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2 in response to pyrogens is critically dependent on COX-2 expression.

  13. NuSTAR observations of the powerful radio-galaxy Cygnus A

    DOE PAGES

    Reynolds, Christopher S.; Lohfink, Anne M.; Ogle, Patrick M.; ...

    2015-07-29

    Here, we present NuSTAR observations of the powerful radio galaxy Cygnus A, focusing on the central absorbed active galactic nucleus (AGN). Cygnus A is embedded in a cool-core galaxy cluster, and hence we also examine archival XMM-Newton data to facilitate the decomposition of the spectrum into the AGN and intracluster medium components. NuSTAR gives a source-dominated spectrum of the AGN out tomore » $$\\gt 70$$ keV. In gross terms, the NuSTAR spectrum of the AGN has the form of a power law ($${\\rm{\\Gamma }}\\sim 1.6-1.7$$) absorbed by a neutral column density of $${N}_{{\\rm{H}}}\\sim 1.6\\times {10}^{23}\\;\\;{\\mathrm{cm}}^{-2}$$. However, we also detect curvature in the hard ($$\\gt 10$$ keV) spectrum resulting from reflection by Compton-thick matter out of our line of sight to the X-ray source. Compton reflection, possibly from the outer accretion disk or obscuring torus, is required even permitting a high-energy cut off in the continuum source; the limit on the cut-off energy is $${E}_{\\mathrm{cut}}\\gt 111$$ keV(90% confidence). Interestingly, the absorbed power law plus reflection model leaves residuals suggesting the absorption/emission from a fast ($$15,000-26,000\\;\\;\\mathrm{km}\\;\\;{{\\rm{s}}}^{-1}\\;$$), high column-density ($${N}_{W}\\gt 3\\times {10}^{23}\\;\\;{\\mathrm{cm}}^{-2}$$), highly ionized ($$\\xi \\sim 2500\\;\\mathrm{erg}\\;\\mathrm{cm}\\;{{\\rm{s}}}^{-1}$$) wind. A second, even faster ionized wind component is also suggested by these data. We show that the ionized wind likely carries a significant mass and momentum flux, and may carry sufficient kinetic energy to exercise feedback on the host galaxy. If confirmed, the simultaneous presence of a strong wind and powerful jets in Cygnus A demonstrates that feedback from radio-jets and sub-relativistic winds are not mutually exclusive phases of AGN activity but can occur simultaneously.« less

  14. The effects of respiratory-muscle training on exercise in older women.

    PubMed

    Watsford, Mark; Murphy, Arona

    2008-07-01

    This research examined the effects of respiratory-muscle (RM) training on RM function and exercise performance in older women. Twenty-six women (60-69 yr of age) were assessed for spirometry, RM strength (maximal inspiratory and expiratory pressure), inspiratory-muscle endurance, and walking performance to a perceived exertion rating of "hard." They were randomly allocated to a threshold RM training group (RMT) or a nonexercising control group (CON) for 8 wk.After training, the 22% (inspiratory) and 30% (expiratory) improvements in RM strength in the RMT group were significantly higher than in the CON group (p < .05). The RMT group also displayed several significant performance improvements, including improved within-group treadmill performance time (12%) and reductions in submaximal heart rate (5%), percentage of maximum voluntary ventilation (16%), and perceived exertion for breathing (8%). RM training appears to improve RM function in older women. Furthermore, these improvements appear to be related to improved submaximal exercise performance.

  15. Stabilization of Cd-, Pb-, Cu- and Zn-contaminated calcareous agricultural soil using red mud: a field experiment.

    PubMed

    Wang, Yangyang; Li, Fangfang; Song, Jian; Xiao, Ruiyang; Luo, Lin; Yang, Zhihui; Chai, Liyuan

    2018-04-12

    Red mud (RM) was used to remediate heavy metal-contaminated soils. Experiments with two different dosages of RM added to soils were carried out in this study. It was found that soil pH increased 0.3 and 0.5 unit with the dosage of 3 and 5% (wt%), respectively. At the dosage of 5%, the highest stabilization efficiencies for Cd, Pb, Cu and Zn reached 67.95, 64.21, 43.73 and 63.73%, respectively. The addition of RM obviously transferred Cd from the exchangeable fraction to the residual fraction. Meanwhile, in comparison with the control (no RM added), it reduced 24.38, 49.20, 19.42 and 8.89% of Cd, Pb, Cu and Zn in wheat grains at the RM addition dosage of 5%, respectively. At the same time, the yield of wheat grains increased 17.81 and 24.66% at the RM addition dosage of 3 and 5%, respectively. Finally, the addition of RM did not change the soil bacterial community. These results indicate that RM has a great potential in stabilizing heavy metals in calcareous agricultural soils.

  16. Using Bar Velocity to Predict the Maximum Dynamic Strength in the Half-Squat Exercise.

    PubMed

    Loturco, Irineu; Pereira, Lucas A; Cal Abad, Cesar C; Gil, Saulo; Kitamura, Katia; Kobal, Ronaldo; Nakamura, Fábio Y

    2016-07-01

    To determine whether athletes from different sport disciplines present similar mean propulsive velocity (MPV) in the half-squat (HS) during submaximal and maximal tests, enabling prediction of 1-repetition maximum (1-RM) from MPV at any given submaximal load. Sixty-four male athletes, comprising American football, rugby, and soccer players; sprinters and jumpers; and combat-sport strikers attended 2 testing sessions separated by 2-4 wk. On the first visit, a standardized 1-RM test was performed. On the second, athletes performed HSs on Smith-machine equipment, using relative percentages of 1-RM to determine the respective MPV of submaximal and maximal loads. Linear regression established the relationship between MPV and percentage of 1-RM. A very strong linear relationship (R2 ≈ .96) was observed between the MPV and the percentages of HS 1-RM, resulting in the following equation: %HS 1-RM = -105.05 × MPV + 131.75. The MPV at HS 1-RM was ~0.3 m/s. This equation can be used to predict HS 1-RM on a Smith machine with a high degree of accuracy.

  17. Do the flash-lag effect and representational momentum involve similar extrapolations?

    PubMed Central

    Hubbard, Timothy L.

    2013-01-01

    In the flash-lag effect (FLE) and in representational momentum (RM), the represented position of a moving target is displaced in the direction of motion. Effects of numerous variables on the FLE and on RM are briefly considered. In many cases, variables appear to have the same effect on the FLE and on RM, and this is consistent with a hypothesis that displacements in the FLE and in RM result from overlapping or similar mechanisms. In other cases, variables initially appear to have different effects on the FLE and on RM, but accounts reconciling those apparent differences with a hypothesis of overlapping or similar mechanisms are suggested. Given that RM is simpler and accounts for a wider range of findings (i.e., RM involves a single stimulus rather than the relationship between two stimuli, RM accounts for displacement in absolute position of a single stimulus and for differences in relative position of two stimuli), it is suggested that (at least some cases of) the FLE might be a special case of RM in which the position of the target is assessed relative to the position of another stimulus (i.e., the flashed object) rather than relative to the actual position of the target. PMID:23734140

  18. Association Analysis of Arsenic-Induced Straighthead in Rice (Oryza sativa L.) Based on the Selected Population with a Modified Model.

    PubMed

    Li, Xiaobai; Hu, Biaolin; Pan, Xuhao; Zhang, Ning; Wu, Dianxing

    2017-01-01

    A rice physiological disorder makes mature panicle keep erect with empty grains termed as "straighthead." Straighthead causes yield losses and is a serious threat to rice production worldwide. Here, a new study of association mapping was conducted to identify QTL involved in straighthead. A subset of 380 accessions was selected from the USDA rice core collection and genotyped with 72 genome-wide SSR markers. An optimal model implemented with principle components (PCs) was used in this association mapping. As a result, five markers were identified to be significantly associated with straighthead. Three of them, RM263, RM169, and RM224, were consistent with a previous study. Three markers, RM475, RM263, and RM19, had a resistant allele associated with a decrease in straighthead rating (straighthead rating ≤ 4.8). In contrast, the two other marker loci RM169 and RM224 had a few susceptible alleles associated with an increase in straighthead rating (straighthead rating ≥ 8.7). Interestingly, RM475 is close to QTL " qSH-2 " and " AsS " with straighthead resistance, which was reported in two studies on linkage mapping of straighthead. This finding adds to previous work and is useful for further genetic study of straighthead.

  19. Programmable Liquid Crystal Elastomers Prepared by Thiol-Ene Photopolymerization (Postprint)

    DTIC Science & Technology

    2015-08-17

    defect forms a 2D wrinkling pattern that leads to an areal contraction (Figure 4c,d). Both of these films return to a largely flat state on cooling...photopolymerization. ■ MATERIALS AND METHODS RM82 (1,4-bis-[4-(6-acryloyloxyhexyloxy)benzoyloxy]-2-methylben- zene) was purchased from Synthon Chemicals. 1,2...noted. Liquid crystal cells were prepared using methods described elsewhere.10 Briefly for cells patterned using rubbed surfaces, Elvamide was

  20. Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings.

    PubMed

    Wang, Jianzhong; Cong, Yanlong; Yin, Renfu; Feng, Na; Yang, Songtao; Xia, Xianzhu; Xiao, Yueqiang; Wang, Wenxiu; Liu, Xiufan; Hu, Shunlin; Ding, Chan; Yu, Shengqing; Wang, Chunfeng; Ding, Zhuang

    2015-05-04

    Newcastle disease virus (NDV) and Goose parvovirus (GPV) are considered to be two of the most important and widespread viruses infecting geese. In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. Expression of the VP3 protein in rmNA-VP3 infected cells was detected by immunofluorescence and Western blot assay. The genetic stability was examined by serially passaging 10 times in 10-day-old embryonated SPF chicken eggs. Goslings were inoculated with rmNA-VP3 showed no apparent signs of disease and developed a strong GPV and NDV neutralizing antibodies response. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Facile synthesis and structure characterization of hexagonal tungsten bronzes crystals

    NASA Astrophysics Data System (ADS)

    Lee, Jiann-Shing; Liu, Hao-Chuan; Peng, Gao-De; Tseng, Yawteng

    2017-05-01

    A facile molten-salt route was used to synthesize hexagonal Cs0.33WO3, Rb0.33WO3 and K0.30WO3 crystals. The three isostructural compounds were successfully prepared from the reaction of MxWO3 powders (M = Cs, Rb, K) in the CsCl/NaCl, RbCl/NaCl and KCl/NaCl fluxes, respectively. The structure determination and refinement, based on single-crystal X-ray diffraction data, are in agreement with previous works, possessing space group P63/mcm. The a and c parameters vary non-linearly with increasing radii of the M+ cations (rM) that is coordinated to twelve oxygen atoms. Both the volumes of unit-cell and WO6 octahedra vary linearly with rM, which become smaller from Cs0.33WO3 to K0.30WO3. The distortion of WO6 octahedra as well as isotropic displacement parameters increases from Cs0.33WO3 to K0.30WO3. The geometry of the WO6 octahedron becomes more regular with increasing rM. These structural trends arise from the effective size of the M+ cation.

  2. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays.

    PubMed

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-12-28

    The generation of tissue resident memory (T RM ) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8 + T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8 + T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8 + T cell expression of CXCR3 + , CD103 +, CD49a + , CD69 + , CD127 + homing, retention and survival markers. Furthermore, memory CD8 + T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8 + T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Validity of one-repetition maximum predictive equations in men with spinal cord injury.

    PubMed

    Ribeiro Neto, F; Guanais, P; Dornelas, E; Coutinho, A C B; Costa, R R G

    2017-10-01

    Cross-sectional study. The study aimed (a) to test the cross-validation of current one-repetition maximum (1RM) predictive equations in men with spinal cord injury (SCI); (b) to compare the current 1RM predictive equations to a newly developed equation based on the 4- to 12-repetition maximum test (4-12RM). SARAH Rehabilitation Hospital Network, Brasilia, Brazil. Forty-five men aged 28.0 years with SCI between C6 and L2 causing complete motor impairment were enrolled in the study. Volunteers were tested, in a random order, in 1RM test or 4-12RM with 2-3 interval days. Multiple regression analysis was used to generate an equation for predicting 1RM. There were no significant differences between 1RM test and the current predictive equations. ICC values were significant and were classified as excellent for all current predictive equations. The predictive equation of Lombardi presented the best Bland-Altman results (0.5 kg and 12.8 kg for mean difference and interval range around the differences, respectively). The two created equation models for 1RM demonstrated the same and a high adjusted R 2 (0.971, P<0.01), but different SEE of measured 1RM (2.88 kg or 5.4% and 2.90 kg or 5.5%). All 1RM predictive equations are accurate to assess individuals with SCI at the bench press exercise. However, the predictive equation of Lombardi presented the best associated cross-validity results. A specific 1RM prediction equation was also elaborated for individuals with SCI. The created equation should be tested in order to verify whether it presents better accuracy than the current ones.

  4. Induction of taxol metabolism in the rat by dexamethasone

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

    Anderson, C.D.; Gondi, K.N.; Walle, T.

    1994-12-31

    The antitumor drug taxol was metabolized to two major metabolites (RM1 and RM2) in adult male and female rat liver microsomes. The male rats produced RM1 2.6 fold faster than the females, and they produced RM2 3 fold faster than the females. This correlated well with the sex differences noticed in liver microsomal cytochrome P450 (CYP) 3A content (4.4 fold greater in male) and 6{beta}-hydroxylation of testosterone (2.4 fold greater in male). Taxol was metabolized to three major metabolites (RM1, RM2, and RM3) in adult male and female rat liver microsomes from rats pretreated with dexamethasone. Production of RM1 andmore » RM2 was increased in these rats (2.3 and 3.3 fold respectively in males; 6.5 and 8.7 fold respectively in females) as compared to the untreated rats. These results compared well with the induction of CYP 3A proteins (3.5 fold in male, 10 fold in female) and induction of 6{beta}-hydroxylation (1.9 fold in males, 3.8 fold in females). RM3, which was produced only by the rats pretreated with dexamethasone, had a retention time of 0.58 relative to taxol which corresponds to 6{alpha}- hydroxytaxol, the major human metabolite of taxol. This study indicates that taxol metabolism in the rat is likely due to CYP 3A enzymes. Although the evidence points toward CYP 3A1 as the major isoform involved, it does not rule out others. The findings also suggest that CYP 3A1 is responsible for the induced metabolite, RM3.« less

  5. Paleo-Balkan and Slavic contributions to the genetic pool of Moldavians: insights from the Y chromosome.

    PubMed

    Varzari, Alexander; Kharkov, Vladimir; Nikitin, Alexey G; Raicu, Florina; Simonova, Kseniya; Stephan, Wolfgang; Weiss, Elisabeth H; Stepanov, Vadim

    2013-01-01

    Moldova has a rich historical and cultural heritage, which may be reflected in the current genetic makeup of its population. To date, no comprehensive studies exist about the population genetic structure of modern Moldavians. To bridge this gap with respect to paternal lineages, we analyzed 37 binary and 17 multiallelic (STRs) polymorphisms on the non-recombining portion of the Y chromosome in 125 Moldavian males. In addition, 53 Ukrainians from eastern Moldova and 54 Romanians from the neighboring eastern Romania were typed using the same set of markers. In Moldavians, 19 Y chromosome haplogroups were identified, the most common being I-M423 (20.8%), R-M17* (17.6%), R-M458 (12.8%), E-v13 (8.8%), R-M269* and R-M412* (both 7.2%). In Romanians, 14 haplogroups were found including I-M423 (40.7%), R-M17* (16.7%), R-M405 (7.4%), E-v13 and R-M412* (both 5.6%). In Ukrainians, 13 haplogroups were identified including R-M17 (34.0%), I-M423 (20.8%), R-M269* (9.4%), N-M178, R-M458 and R-M73 (each 5.7%). Our results show that a significant majority of the Moldavian paternal gene pool belongs to eastern/central European and Balkan/eastern Mediterranean Y lineages. Phylogenetic and AMOVA analyses based on Y-STR loci also revealed that Moldavians are close to both eastern/central European and Balkan-Carpathian populations. The data correlate well with historical accounts and geographical location of the region and thus allow to hypothesize that extant Moldavian paternal genetic lineages arose from extensive recent admixture between genetically autochthonous populations of the Balkan-Carpathian zone and neighboring Slavic groups.

  6. Fatty and lean red meat consumption in China: differential association with Chinese abdominal obesity

    PubMed Central

    Wang, Z.; Zhang, B.; Zhai, F.; Wang, H.; Zhang, J.; Du, W.; Su, C.; Zhang, J.; Jiang, H.; Popkin, B. M.

    2014-01-01

    Aim We examined the longitudinal association between red meat (RM) consumption and the risk of abdominal obesity in Chinese adults. Methods and results Our data are from 16,822 adults aged 18 to 75 in the China Health and Nutrition Survey from 1993 to 2011. We assessed RM intake with three 24-hour dietary recalls. We defined abdominal obesity as a waist circumference (WC) ≥ 85 centimeters (cm) for men and ≥ 80 cm for women. Multilevel mixed-effect regression models showed that men experienced WC increases of 0.74 cm (95% confidence interval [CI]: 0.39–1.09) from a higher total intake of fresh RM and 0.59 cm (95% CI: 0.24–0. 95) from a higher intake of fatty fresh RM but 0.14 cm (95% CI: −0.39–0.66) from a higher intake of lean fresh RM in the top versus the bottom quartile when adjusted for potential confounders. In contrast, after additional adjustment for baseline WC, the odds ratios of abdominal obesity in men were attenuated for total fresh RM (1.25 [95% CI: 1.06–1.47]) and fatty fresh RM (1.22 [95% CI: 1.03–1.44]) but were still not affected by lean fresh RM (0.95 [95% CI: 0.75–1.22]). Women also showed a positive association of fatty fresh RM intake with abdominal obesity. Conclusion Greater intake of fatty fresh RM was significantly associated with higher WC (men only) and abdominal obesity risk in Chinese adults. The gender-specific differential association of fatty versus lean fresh RM warrants further study. PMID:24795160

  7. Fatty and lean red meat consumption in China: differential association with Chinese abdominal obesity.

    PubMed

    Wang, Z; Zhang, B; Zhai, F; Wang, H; Zhang, J; Du, W; Su, C; Zhang, J; Jiang, H; Popkin, B M

    2014-08-01

    We examined the longitudinal association between red meat (RM) consumption and the risk of abdominal obesity in Chinese adults. Our data are from 16,822 adults aged 18-75 in the China Health and Nutrition Survey from 1993 to 2011. We assessed RM intake with three 24-h dietary recalls. We defined abdominal obesity as a waist circumference (WC) ≥85 centimeters (cm) for men and ≥80 cm for women. Multilevel mixed-effect regression models showed that men experienced WC increases of 0.74 cm (95% confidence interval [CI]: 0.39-1.09) from a higher total intake of fresh RM and 0.59 cm (95% CI: 0.24-0. 95) from a higher intake of fatty fresh RM but 0.14 cm (95% CI: -0.39 to 0.66) from a higher intake of lean fresh RM in the top quartile versus non-consumers when adjusted for potential confounders. In contrast, after additional adjustment for baseline WC, the odds ratios of abdominal obesity in men were attenuated for total fresh RM (1.25 [95% CI: 1.06-1.47]) and fatty fresh RM (1.22 [95% CI: 1.03-1.44]) but were still not affected by lean fresh RM (0.95 [95% CI: 0.75-1.22]). Women also showed a positive association of fatty fresh RM intake with abdominal obesity. Greater intake of fatty fresh RM was significantly associated with higher WC (men only) and abdominal obesity risk in Chinese adults. The gender-specific differential association of fatty versus lean fresh RM warrants further study. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Physiologic effects of rhythmical massage: a prospective exploratory cohort study.

    PubMed

    Wälchli, Chantal; Saltzwedel, Georg; Krüerke, Daniel; Kaufmann, Christoph; Schnorr, Bettina; Rist, Lukas; Eberhard, Jutta; Decker, Michael; Simões-Wüst, Ana Paula

    2014-06-01

    This study was performed to characterize the physiologic effects of rhythmical massage (RM), an anthroposophic therapy whose effectiveness is supported by empirical observations and a prospective observational study. Patients referred to RM at the Paracelsus Hospital Richterswil for any indication were continuously enrolled. They received an average of 10 RM sessions, which included not only the massage but also therapeutic rest in the supine position immediately thereafter. Effects of RM on surface temperature and on heart rate variability (HRV) were determined with infrared imaging (IRI) and electrocardiography (ECG), respectively. IRI of the patients' dorsal region was performed without clothes, in standing position, at the start and at the end of two waiting periods before and after RM. ECG was performed from the beginning of the first waiting period until the end of the second one. Results on IRI from 9 and ECG from 11 patients could be analyzed. RM led to an immediate increase in dorsal temperature. Furthermore, comparison of the IRI images for consecutive RM sessions showed a tendency toward improved warmth distribution as a progressive therapy effect. Analysis of the EGC results recorded during the waiting periods-in the sitting position--showed a significant increase of HRV after RM, as detected by the standard deviation of the beat-to-beat periods and a relative increase of low-frequency power. During the course of the RM sessions, the change in HRV during the therapeutic rest period depended on the initial value: Low initial values were enhanced, whereas high ones were reduced. RM led to an immediate increase in the patient's dorsal surface temperature, as well as increased HRV and sympathetic stimulation. In the long term, RM resulted in a progressive improvement of warmth distribution and regulation of the resting HRV.

  9. Impact of remote monitoring on clinical events and associated health care utilization: A nationwide assessment.

    PubMed

    Piccini, Jonathan P; Mittal, Suneet; Snell, Jeff; Prillinger, Julie B; Dalal, Nirav; Varma, Niraj

    2016-12-01

    Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) improves patient survival. However, whether RM reduces health care utilization is unknown. The purpose of this study was to determine whether RM was associated with reduced hospitalization and costs in clinical practice. We conducted a nationwide cohort study using the Truven Health Analytics MarketScan database. Patients implanted with a CIED between March 31, 2009, and April 1, 2012, were included. All-cause hospitalization events were compared between those using RM and those not using RM by using Cox proportional hazards methods with Andersen-Gill extension and propensity scoring. We also compared health care costs (payments >30 days after CIED implantation). Overall, there were 92,566 patients (mean age 72 ± 13 years; 58,140 [63%] men) with a mean follow-up of 19 ± 12 months, including 54,520 (59%) pacemaker, 27,816 (30%) implantable cardioverter-defibrillator, and 10,230 (11%) cardiac resynchronization therapy patients. Only 37% of patients (34,259) used RM. Patients with RM had Charlson Comorbidity Index values similar to those not using RM but had lower adjusted risk of all-cause hospitalization (adjusted hazard ratio 0.82; 95% confidence interval 0.80-0.84; P < .001) and shorter mean length of hospitalization (5.3 days vs 8.1 days; P < .001) during follow-up. RM was associated with a 30% reduction in hospitalization costs ($8720 mean cost per patient-year vs $12,423 mean cost per patient-year). For every 100,000 patient-years of follow-up, RM was associated with 9810 fewer hospitalizations, 119,000 fewer days in hospital, and $370,270,000 lower hospital payments. RM is associated with reductions in hospitalization and health care utilization. Since only about a third of patients with CIEDs routinely use RM, this represents a major opportunity for quality improvement. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  10. Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

    PubMed

    Ferrando, Carlos; Suarez-Sipmann, Fernando; Tusman, Gerardo; León, Irene; Romero, Esther; Gracia, Estefania; Mugarra, Ana; Arocas, Blanca; Pozo, Natividad; Soro, Marina; Belda, Francisco J

    2017-01-01

    Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. ClinicalTrials.gov NCT02798133.

  11. Strength, power, and muscular endurance exercise and elite rowing ergometer performance.

    PubMed

    Lawton, Trent W; Cronin, John B; McGuigan, Michael R

    2013-07-01

    Knowledge of the relationship between weight room exercises and various rowing performance measures is limited; this information would prove useful for sport-specific assessment of individual needs and exercise prescription. The purpose of this study was to establish strength, power, and muscular endurance exercises for weight room training, which are strong determinants of success in specific performance measures used to assess elite rowers. Nineteen heavyweight elite males determined their repetition maximum (RM) loads for exercises using a Concept 2 DYNO [5, 30, 60 and 120RM leg pressing and seated arm pulling (in Joules)] and free weights [1RM power clean (in kilograms) and 6RM bench pull (in kilograms and watts)]. Rowing performance measures included a 7-stage blood lactate response ergometer test (aerobic condition), time trials (500, 2000, and 5000 m), a peak stroke power test, and a 60-minute distance trial. Pearson correlation moments (r ≥ 0.7) and stepwise multiple linear regression calculations (R ≥ 50%) were used to establish strong common variances between weight room exercises and rowing ergometer performance (p ≤ 0.05). Weight room exercises were strong predictors of 2000-m, 500-m time (in seconds), and peak stroke power performance measures only. Bench pull power (in watts) and 1RM power clean (in kilograms) were the best 2-factor predictors of peak stroke power (R = 73%; standard error of the estimates [SEE] = 59.6 W) and 500 m (R = 70%; SEE = 1.75 seconds); while 5RM leg pressing (in Joules) and either 6RM bench pull (kg) or 60RM seated arm pulling (in Joules) the best predictors of 2000 m (R = 59%; SEE = 6.3 seconds and R = 57%; SEE = 6.4 seconds, respectively). Recommended exercises for weight room training include a 1RM power clean, 6RM bench pull, 5RM leg press, and 60RM seated arm pulling.

  12. Economic analysis of remote monitoring of cardiac implantable electronic devices: Results of the Health Economics Evaluation Registry for Remote Follow-up (TARIFF) study.

    PubMed

    Ricci, Renato Pietro; Vicentini, Alfredo; D'Onofrio, Antonio; Sagone, Antonio; Rovaris, Giovanni; Padeletti, Luigi; Morichelli, Loredana; Fusco, Antonio; De Vivo, Stefano; Lombardi, Leonida; Denaro, Alessandra; Pollastrelli, Annalisa; Colangelo, Irene; Santini, Massimo

    2017-01-01

    Remote monitoring (RM) of cardiac implantable electronic devices has been demonstrated to improve outpatient clinic workflow and patient management. However, few data are available on the socioeconomic impact of RM. The aim of this study was to assess the costs and benefits of RM compared with standard care (SC). We used 12-month patient data from the Health Economics Evaluation Registry for Remote Follow-up (TARIFF) study (N = 209; RM: n = 102 (48.81%); SC: n = 107 (51.19%)). Cost comparison was made from 2 perspectives: the health care system (HCS) and patients. The use of health care resources was defined on the basis of hospital clinical folders. Out-of-pocket expenses were reported directly by patients. HCS perspective: The overall mean annual cost per patient in the SC group (€1044.89 ± €1990.47) was significantly higher than in the RM group (€482.87 ± €2488.10) (P < .0001), with a reduction of 53.87% being achieved in the RM group. The primary driver of cost reduction was the cost of cardiovascular hospitalizations (SC: €`886.67 ± €1979.13 vs RM: €432.34 ± €2488.10; P = .0030). Patient and caregiver perspective: The annual cost incurred by patients was significantly higher in the SC group than in the RM group (SC: €169.49 ± €189.50 vs RM: €56.87 ± €80.22; P < .0001). Patients' quality-adjusted life-years were not significantly different between the groups. Provider perspective: The total number of inhospital device follow-up visits was reduced by 58.78% in the RM group. RM of patients with cardiac implantable electronic devices (CIEDs) is cost saving from the perspectives of the HCS, patients, and caregivers. Introducing appropriate reimbursements will make RM sustainable even for the provider, i.e. the hospitals which provide the service and encourage widespread adoption of RM. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Prevalence of Prostate Cancer Metastases after Intravenous Inoculation Provides Clues into the Molecular Basis of Dormancy in the Bone Marrow Microenvironment1

    PubMed Central

    Jung, Younghun; Shiozawa, Yusuke; Wang, Jingcheng; McGregor, Natalie; Dai, Jinlu; Park, Serk In; Berry, Janice E; Havens, Aaron M; Joseph, Jeena; Kim, Jin Koo; Patel, Lalit; Carmeliet, Peter; Daignault, Stephanie; Keller, Evan T; McCauley, Laurie K; Pienta, Kenneth J; Taichman, Russell S

    2012-01-01

    Bone is the preferred metastasis site of advanced prostate cancer (PCa). Using an in vivo murine model of human PCa cell metastasis to bone, we noted that the majority of animals that develop skeletal metastasis have either spinal lesions or lesions in the bones of the hindlimb. Much less frequently, lesions develop in the bones of the forelimb. We therefore speculated whether the environment of the forelimb bones is not permissive for the growth of PCa. Consequently, data on tumor prevalence were normalized to account for the number of PCa cells arriving after intravascular injection, marrow cellularity, and number of hematopoietic stem cell niches. None of these factors were able to account for the observed differences in tumor prevalence. An analysis of differential gene and protein levels identified that growth arrest specific-6 (GAS6) levels were significantly greater in the forelimb versus hindlimb bone marrow. When murine RM1 cells were implanted into subcutaneous spaces in immune competent animals, tumor growth in the GAS6-/- animals was greater than in GAS6+/+ wild-type animals. In an osseous environment, the human PC3 cell line grew significantly better in vertebral body transplants (vossicles) derived from GAS6-/- animals than in vossicles derived from GAS6+/+ animals. Together, these data suggest that the differences in tumor prevalence after intravascular inoculation are a useful model to study the molecular basis of tumor dormancy. Importantly, these data suggest that therapeutic manipulation of GAS6 levels may prove useful as a therapy for metastatic disease. PMID:22745589

  14. Fine mapping of a quantitative trait locus for spikelet number per panicle in a new plant type rice and evaluation of a near-isogenic line for grain productivity.

    PubMed

    Sasaki, Kazuhiro; Fujita, Daisuke; Koide, Yohei; Lumanglas, Patrick D; Gannaban, Ritchel B; Tagle, Analiza G; Obara, Mitsuhiro; Fukuta, Yoshimichi; Kobayashi, Nobuya; Ishimaru, Tsutomu

    2017-05-17

    Total spikelet number per panicle (TSN) is one of the determinants of grain productivity in rice (Oryza sativa L.). In this study, we attempted to detect quantitative trait loci (QTLs) for TSN in the introgression lines with high TSN, derived from the cross of Indica Group variety IR 64 with new plant type lines. Two QTLs were detected on the long arm of chromosome 12: qTSN12.1 in the BC4F2 population of YTH63/IR 64 and qTSN12.2 in the BC4F3 population of YTH83/IR 64. TSN of the main tiller was significantly higher in near-isogenic lines (NILs) for qTSN12.1 (IR 64-NIL1; 188.6) and for qTSN12.2 (IR 64-NIL12; 199.4) than in IR 64 (141.2), owing to a significant increase in both primary and secondary branch numbers. These results suggest the critical function of these QTLs in the promotion of rachis branching at the panicle formation stage. Fine mapping of qTSN12.2 revealed six candidate genes in a 92-kb region of the Nipponbare reference genome sequence between flanking markers RM28746 and RM28753. Detailed phenotyping of agronomic traits of IR 64-NIL12 carrying qTSN12.2 showed drastic changes in plant architecture: this line had lower panicle number, longer culm, and longer and wider leaves compared with IR 64. Percentage of fertility and 1000-grain weight tended to be greater, and grain yield per square meter was also greater in IR 64-NIL12 than in IR 64. The newly identified QTLs will be useful for genetic improvement of the yield potential of Indica Group varieties. The markers tightly linked to qTSN12.2 are available for marker-assisted breeding. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Complete genome sequence of Campylobacter jejuni RM1246-ERRC that exhibits resistance to Quaternary Ammonium Compounds

    USDA-ARS?s Scientific Manuscript database

    Campylobacter jejuni strain RM1246-ERRC is a clinical isolate. In laboratory experiments RM1246-ERRC exhibited resistance to the antimicrobial effects of quaternary ammonium compounds (QACs) when compared to other C. jejuni strains. The chromosome of RM1246-ERRC was determined to be 1,659,694 bp w...

  16. 76 FR 37682 - Airworthiness Directives; Teledyne Continental Motors (TCM) and Rolls-Royce Motors Ltd. (R-RM...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... Continental Motors (TCM) and Rolls-Royce Motors Ltd. (R-RM) Series Reciprocating Engines AGENCY: Federal... supersede an existing airworthiness directive (AD) that applies to certain TCM and R-RM series reciprocating... range of magneto S/ Ns affected, and of the need to include certain engines made by R-RM, under license...

  17. 76 FR 78808 - Airworthiness Directives; Teledyne Continental Motors (TCM) and Rolls-Royce Motors Ltd. (R-RM...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... Airworthiness Directives; Teledyne Continental Motors (TCM) and Rolls-Royce Motors Ltd. (R-RM) Series... superseding an existing airworthiness directive (AD) for certain TCM and R-RM series reciprocating engines... adds R-RM C-125, C- 145, O-300, IO-360, TSIO-360, and LTSIO-520-AE series reciprocating engines to the...

  18. Inhibitory Activities of Epidermal Growth Factor Receptor Tyrosine Kinase-Targeted Dihydroxyisoflavone and Trihydroxydeoxybenzoin Derivatives on Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum Development

    PubMed Central

    Gargala, G.; Baishanbo, A.; Favennec, L.; François, A.; Ballet, J. J.; Rossignol, J.-F.

    2005-01-01

    Several gene sequences of parasitic protozoa belonging to protein kinase gene families and epidermal growth factor (EGF)-like peptides, which act via binding to receptor tyrosine kinases of the EGF receptor (EGFR) family, appear to mediate host-protozoan interactions. As a clue to EGFR protein tyrosine kinase (PTK) mediation and a novel approach for identifying anticoccidial agents, activities against Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum grown in BM and HCT-8 cell cultures of 52 EGFR PTK inhibitor isoflavone analogs (dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives) were investigated. Their cytotoxicities against host cells were either absent, mild, or moderate by a nitroblue tetrazolium test. At concentrations ranging from 5 to 10 μg/ml, 20 and 5 analogs, including RM-6427 and RM-6428, exhibited an in vitro inhibitory effect of ≥95% against at least one parasite or against all three, respectively. In immunosuppressed Cryptosporidium parvum-infected Mongolian gerbils orally treated with either 200 or 400 mg of agent RM-6427/kg of body weight/day for 8 days, fecal microscopic oocyst shedding was abolished in 6/10 animals (P of <0.001 versus untreated controls) and mean shedding was reduced by 90.5% (P of <0.0001) and 92.0% (P of <0.0001), respectively, higher levels of inhibition than after nitazoxanide (200 mg/kg/day for 8 days) or paromomycin (100 mg/kg/day for 8 days) treatment (55.0%, P of <0.001, and 17.5%, P of >0.05, respectively). After RM-6427 therapy (200 mg/kg/day for 8 days), the reduction in the ratio of animals with intracellular parasites was nearly significant in ileum (P = 0.067) and more marked in the biliary tract (P < 0.0013) than after nitazoxanide or paromomycin treatment (0.05 < P < 0.004). RM-6428 treatment at a regimen of 400 mg/kg/day for 12 days inhibited oocyst shedding, measured using flow cytometry from day 4 (P < 0.05) to day 12 (P < 0.02) of therapy, when 2/15 animals had no shedding (P < 0.0001) and 11/15 were free of gut and/or biliary tract parasites (P < 0.01). No mucosal alteration was microscopically observed for treated or untreated infected gerbils. To our knowledge, this report is the first to suggest that the isoflavone class of agents has the potential for anticoccidial therapy. PMID:16251305

  19. The Cost and Utility of Renal Transplantation in Malaysia.

    PubMed

    Bavanandan, Sunita; Yap, Yok-Chin; Ahmad, Ghazali; Wong, Hin-Seng; Azmi, Soraya; Goh, Adrian

    2015-11-01

    Kidney transplantation is the optimal therapy for the majority of patients with end-stage renal disease. However, the cost and health outcomes of transplantation have not been assessed in a middle-income nation with a low volume of transplantation, such as Malaysia. This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death. Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively. Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.

  20. The effects of attention on age-related relational memory deficits: Evidence from a novel attentional manipulation

    PubMed Central

    Kim, So-Yeon; Giovanello, Kelly S.

    2011-01-01

    Healthy aging is often accompanied by episodic memory decline. Prior studies have consistently demonstrated that older adults show disproportionate deficits in relational memory (RM) relative to item memory (IM). Despite rich evidence of an age-related RM deficit, the source of this deficit remains unspecified. One of the most widely investigated factors of age-related RM impairment is a reduction in attentional resources. However, no prior studies have demonstrated that reduced attentional resources are the critical source of age-related RM deficits. Here, we utilized qualitatively different attention tasks, and tested whether reduced attention for relational processing underlies the RM deficit observed in aging. In Experiment 1, we imposed either item-detection or relation-detection attention tasks on young adults during episodic memory encoding, and found that only the concurrent attention task involving relational processing disproportionately impaired RM performance in young adults. Moreover, by ruling out the possible confound of task-difficulty on the disproportionate RM impairment, we further demonstrated that reduced relational attention is a key factor for the age-related RM deficit. In Experiment 2, we replicated the results from Experiment 1 using different materials of stimuli and found that the effect of relational attention on RM is material-general. The results of Experiment 2 also showed that reducing attentional resources for relational processing in young adults strikingly equated their RM performance to that of older adults. Thus, the current study documents the first evidence that reduced attentional resources for relational processing are a critical factor for the relational memory impairment observed in aging. PMID:21707178

  1. Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

    PubMed

    Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C

    2008-06-01

    The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level.

  2. Predicting the Maximum Dynamic Strength in Bench Press: The High Precision of the Bar Velocity Approach.

    PubMed

    Loturco, Irineu; Kobal, Ronaldo; Moraes, José E; Kitamura, Katia; Cal Abad, César C; Pereira, Lucas A; Nakamura, Fábio Y

    2017-04-01

    Loturco, I, Kobal, R, Moraes, JE, Kitamura, K, Cal Abad, CC, Pereira, LA, and Nakamura, FY. Predicting the maximum dynamic strength in bench press: the high precision of the bar velocity approach. J Strength Cond Res 31(4): 1127-1131, 2017-The aim of this study was to determine the force-velocity relationship and test the possibility of determining the 1 repetition maximum (1RM) in "free weight" and Smith machine bench presses. Thirty-six male top-level athletes from 3 different sports were submitted to a standardized 1RM bench press assessment (free weight or Smith machine, in randomized order), following standard procedures encompassing lifts performed at 40-100% of 1RM. The mean propulsive velocity (MPV) was measured in all attempts. A linear regression was performed to establish the relationships between bar velocities and 1RM percentages. The actual and predicted 1RM for each exercise were compared using a paired t-test. Although the Smith machine 1RM was higher (10% difference) than the free weight 1RM, in both cases the actual and predicted values did not differ. In addition, the linear relationship between MPV and percentage of 1RM (coefficient of determination ≥95%) allow determination of training intensity based on the bar velocity. The linear relationships between the MPVs and the relative percentages of 1RM throughout the entire range of loads enable coaches to use the MPV to accurately monitor their athletes on a daily basis and accurately determine their actual 1RM without the need to perform standard maximum dynamic strength assessments.

  3. Synthesis, Characterization, and Crystallization of Syndiotactic Alternating Ethylene-Propylene Crystalline Copolymer and its Blends.

    NASA Astrophysics Data System (ADS)

    Chien, Haoyang

    A syndiotactic alternating ethylene-propylene (SYN-ALT-EP) crystalline copolymer was synthesized by complete hydrogenation, using a diimide reduction, of syndiotactic cis-1,4-poly(pentadiene-1,3) (CIS-PPD). The microstructure was studied by both high resolution nuclear magnetic resonance (NMR) spectroscopy and also fourier transform infra-red (FTIR) spectroscopy. The number average length of syndiotactic sequences is about 69 which indicates a high degree of syndiotacticity (97%) in the microstructure of this copolymer. The single FTIR absorbance at 733 cm^{ -1} without any splitting suggests an alternating arrangement of ethylene and propylene units. The solution state characterization of SYN-ALT -EP was studied by gel permeation chromatography using on -line measurements of multi-angle laser light scattering (MALLS), single capillary viscosities (VISC), and concentrations by differential refractive index (DRI) detectors. The Mark-Houwink-Sakurada parameters of "K" and "a" in THF at 30^circC are determined to be 8.99 times 10^ {-5} and 0.8, respectively. The universal GPC calibration curve can be applied to this copolymer in THF at 30^circC. Two different molecular relaxation processes ( alpha and beta relaxations) were found via dynamic mechanical (DM) analysis below room temperature: an alpha relaxation (around -60^ circC) and a beta relaxation (around -125^circ C). The apparent activation energy of the alpha relaxation is 285 kJ/mol, and the activation energy of the beta relaxation is 43 kJ/mol based on the Arrhenius equation. Molecular motion in SYN-ALT-EP copolymer was probed by solid state ^{13}C NMR experiments. At temperatures above T_{rm g} there are two major molecular motions in this copolymer: a backbone motion (the rotational motion about single bonds) and a methyl side group rotation. The backbone motion is frozen below T_{rm g}, but the methyl rotation still occurs. As the temperature is further decreased to about -175 ^circC, well below the beta -transition observed in DM analysis, the methyl side group rotation slows down, suggesting that the methyl rotation may be associated with the observed beta relaxation process. The equilibrium melting temperature is 55 +/- 1^circC; the equilibrium heat of fusion is 8.8 +/- 0.3 kJ/mol. The overall crystallization kinetics show an Avrami exponent (n) that qualitatively increases with crystallization temperature during primary crystallization. The transition from Regime II to Regime III is observed near T_{rm c} = 26 ^circC based on linear crystal growth rate experiments. The fold surface free energy ( sigma_{rm e}) is determined to be 33 erg/cm^2. A monoclinic crystal unit cell was determined (a = 11.19A b = 11.82A c = 9.00A gamma = 67.03^circ) from the fiber pattern via wide angle x-ray diffraction experiments (WAXD). A banded spherulitic morphology was observed by polarized light microscopy (PLM) and transmission electron microscopy (TEM). Such texture is characteristic of the co-twisting of growing lamellae. The morphology changes from regularly banded spherulites to non-regularly banded spherulites and may be correlated with the Regime III to Regime II transition. A plate-like single crystal morphology was also observed by polarized light microscopy after a melt crystallization at small supercooling conditions. Blends of SYN-ALT-EP/IPP, SYN-ALT-EP/HDPE, and SYN-ALT-EP/LDPE were made and examined. Neither T _{rm g} shifting nor co-crystallization using different blending compositions were observed. Therefore, only limited, if any, miscibility exists in these blends.

  4. Effect of surface stability on core muscle activity for dynamic resistance exercises.

    PubMed

    Willardson, Jeffrey M; Fontana, Fabio E; Bressel, Eadric

    2009-03-01

    To compare core muscle activity during resistance exercises performed on stable ground vs. the BOSU Balance Trainer. Twelve trained men performed the back squat, dead lift, overhead press, and curl lifts. The activity of the rectus abdominis, external oblique abdominis, transversus abdominis/internal oblique abdominis, and erector spinae muscles was assessed. Subjects performed each lift under three separate conditions including standing on stable ground with 50% of a 1-RM, standing on a BOSU Balance Trainer with 50% of a 1-RM, and standing on stable ground with 75% of a 1-RM. Significant differences were noted between the stable 75% of 1-RM and BOSU 50% of 1-RM conditions for the rectus abdominis during the overhead press and transversus abdominis/internal oblique abdominis during the overhead press and curl (P < .05). Conversely, there were no significant differences between the stable 75% of 1-RM and BOSU 50% of 1-RM conditions for the external obliques and erector spinae across all lifts examined. Furthermore, there were no significant differences between the BOSU 50% of 1-RM and stable 50% of 1-RM conditions across all muscles and lifts examined. The current study did not demonstrate any advantage in utilizing the BOSU Balance Trainer. Therefore, fitness trainers should be advised that each of the aforementioned lifts can be performed while standing on stable ground without losing the potential core muscle training benefits.

  5. An effective novel delivery strategy of rasagiline for Parkinson's disease.

    PubMed

    Fernández, Marcos; Negro, Sofía; Slowing, Karla; Fernández-Carballido, Ana; Barcia, Emilia

    2011-10-31

    This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to Wistar rats produced typical PD symptoms. Catalepsy, akinesia and swim tests outcomes in animals receiving RM either in solution or within microspheres showed a reversal in descent latency when compared to rotenone-treated animals, being this reversal specially pronounced in animals receiving RM microspheres (dose equivalent to 1 mg/kg/day RM injected i.p. every 15 days). Nissl-staining of brain sections showed selective degeneration of the substantia nigra (SNc) dopaminergic neurons in rotenone-treated animals which was markedly reverted by RM microspheres. PET/CT with (18)F-DG resulted in mean increases of accumulation of radiotracer in striatum and SNc of around 40% in animals treated with RM microspheres which also had significant beneficial effects on Bcl-2, Bax, TNF-α mRNA and SOD2 levels as detected by real-time RT-PCR. Our results confirm the robust effect achieved by the new controlled release system developed for RM which exhibited better in vivo efficacy than RM given in solution. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Predicting maximal strength in trained postmenopausal woman.

    PubMed

    Kemmler, Wolfgang K; Lauber, Dirk; Wassermann, Alfred; Mayhew, Jerry L

    2006-11-01

    The purpose of this study was to present an equation that accurately predicts 1 repetition maximum (RM) over a wide range of repetitions to fatigue (RTF) for 4 different machine resistance exercises in postmenopausal women. Seventy trained women (age = 57.4 +/- 3.1 years) performed maximal and submaximal repetitions on leg press, bench press, rowing, and leg adduction machines at the conclusion of a 2-year training program. Maximal repetitions were performed on each exercise in the following ranges: 3-5RM, 6-10RM, 11-15RM, and 16-20RM. Special regard was taken to maintain the identical execution of each test (i.e., range of motion, starting angle, speed of movement). One cubic polynomial (w(i) [0.988-0.0000584 r(i)(3) + 0.00190 r(i)(2) + 0.0104 r(i),] where w(i) is the load of measurement I, and r(i) is the number of repetitions) accurately predicted 1RM from RTF with mean absolute differences between actual 1RM and predicted 1RM for the 4 exercises of 1.5-3.1% and with coefficients of variation of <3.3%. Equation accuracy was independent of the exercise type or the number of RTF. Thus, this study supported the validity of RTF to adequately estimate 1RM over a wide range of repetitions and within different exercises in trained, older female subjects.

  7. First Measurement of the Beam Normal Single Spin Asymmetry in $Δ$ Resonance Production by $$Q_{\\rm weak}$$

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

    Nuruzzaman, nfn

    The beam normal single spin asymmetry (more » $$B_{\\rm n}$$) is generated in the scattering of transversely polarized electrons from unpolarized nuclei. The asymmetry arises from the interference of the imaginary part of the two-photon exchange with the one-photon exchange amplitude. The $$Q_{\\rm weak}$$ experiment has made the first measurement of $$B_{\\rm n}$$ in the production of the $$\\Delta$$(1232) resonance, using the $$Q_{\\rm weak}$$ apparatus in Hall-C at the Thomas Jefferson National Accelerator Facility. The final transverse asymmetry, corrected for backgrounds and beam polarization, is $$B_{\\rm n}$$ = 43 $$\\pm$$ 16 ppm at beam energy 1.16 GeV at an average scattering angle of about 8.3 degrees, and invariant mass of 1.2 GeV. The measured preliminary $$B_{\\rm n}$$ agrees with a preliminary theoretical calculation. $$B_{\\rm n}$$ for the $$\\Delta$$ is the only known observable that is sensitive to the $$\\Delta$$ elastic form-factors ($$\\gamma$$*$$\\Delta\\Delta$$) in addition to the generally studied transition form-factors ($$\\gamma$$*N$$\\Delta$$), but extracting this information will require significant theoretical input.« less

  8. Impact of Measurement Uncertainties on Receptor Modeling of Speciated Atmospheric Mercury.

    PubMed

    Cheng, I; Zhang, L; Xu, X

    2016-02-09

    Gaseous oxidized mercury (GOM) and particle-bound mercury (PBM) measurement uncertainties could potentially affect the analysis and modeling of atmospheric mercury. This study investigated the impact of GOM measurement uncertainties on Principal Components Analysis (PCA), Absolute Principal Component Scores (APCS), and Concentration-Weighted Trajectory (CWT) receptor modeling results. The atmospheric mercury data input into these receptor models were modified by combining GOM and PBM into a single reactive mercury (RM) parameter and excluding low GOM measurements to improve the data quality. PCA and APCS results derived from RM or excluding low GOM measurements were similar to those in previous studies, except for a non-unique component and an additional component extracted from the RM dataset. The percent variance explained by the major components from a previous study differed slightly compared to RM and excluding low GOM measurements. CWT results were more sensitive to the input of RM than GOM excluding low measurements. Larger discrepancies were found between RM and GOM source regions than those between RM and PBM. Depending on the season, CWT source regions of RM differed by 40-61% compared to GOM from a previous study. No improvement in correlations between CWT results and anthropogenic mercury emissions were found.

  9. Impact of Measurement Uncertainties on Receptor Modeling of Speciated Atmospheric Mercury

    PubMed Central

    Cheng, I.; Zhang, L.; Xu, X.

    2016-01-01

    Gaseous oxidized mercury (GOM) and particle-bound mercury (PBM) measurement uncertainties could potentially affect the analysis and modeling of atmospheric mercury. This study investigated the impact of GOM measurement uncertainties on Principal Components Analysis (PCA), Absolute Principal Component Scores (APCS), and Concentration-Weighted Trajectory (CWT) receptor modeling results. The atmospheric mercury data input into these receptor models were modified by combining GOM and PBM into a single reactive mercury (RM) parameter and excluding low GOM measurements to improve the data quality. PCA and APCS results derived from RM or excluding low GOM measurements were similar to those in previous studies, except for a non-unique component and an additional component extracted from the RM dataset. The percent variance explained by the major components from a previous study differed slightly compared to RM and excluding low GOM measurements. CWT results were more sensitive to the input of RM than GOM excluding low measurements. Larger discrepancies were found between RM and GOM source regions than those between RM and PBM. Depending on the season, CWT source regions of RM differed by 40–61% compared to GOM from a previous study. No improvement in correlations between CWT results and anthropogenic mercury emissions were found. PMID:26857835

  10. Genetics Home Reference: Langerhans cell histiocytosis

    MedlinePlus

    ... Oct;29(5):853-73. doi: 10.1016/j.hoc.2015.06.005. Epub 2015 Aug 18. Review. Citation on PubMed Nelson DS, van Halteren A, Quispel WT, van den Bos C, Bovée JV, Patel B, Badalian-Very G, van Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, ...

  11. The impact of aerosol composition on the particle to gas partitioning of reactive mercury.

    PubMed

    Rutter, Andrew P; Schauer, James J

    2007-06-01

    A laboratory system was developed to study the gas-particle partitioning of reactive mercury (RM) as a function of aerosol composition in synthetic atmospheric particulate matter. The collection of RM was achieved by filter- and sorbent-based methods. Analyses of the RM collected on the filters and sorbents were performed using thermal extraction combined with cold vapor atomic fluorescence spectroscopy (CVAFS), allowing direct measurement of the RM load on the substrates. Laboratory measurements of the gas-particle partitioning coefficients of RM to atmospheric aerosol particles revealed a strong dependence on aerosol composition, with partitioning coefficients that varied by orders of magnitude depending on the composition of the particles. Particles of sodium nitrate and the chlorides of potassium and sodium had high partitioning coefficients, shifting the RM partitioning toward the particle phase, while ammonium sulfate, levoglucosan, and adipic acid caused the RM to partition toward the gas phase and, therefore, had partitioning coefficients that were lower by orders of magnitude.

  12. Walking a tightrope: clinical use of ibrutinib in mantle cell lymphoma in the elderly.

    PubMed

    Ruella, Marco; Soubeyran, Pierre

    2016-12-02

    Representative clinical case. A 74-year-old male patient was diagnosed with stage 3 mantle cell lymphoma in 2012. Because he was ineligible for intensive treatment (age, previous myocardial infarction [MI]), he received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy for 6 cycles (reaching complete response) and then rituximab maintenance (RM) for 2 years. One year after the end of RM, he relapsed with disseminated disease. He was started on ibrutinib 560 mg/day. Two weeks after the start of ibrutinib, he developed grade 3 diarrhea that required interruption of ibrutinib. Two weeks after the regular dose was restarted (month 3), the patient had repeated bleeding (patient was receiving aspirin for previous MI) and had to stop ibrutinib again. Because the patient was in partial response (PR) with lack of disease-associated symptoms, he was restarted on ibrutinib 280 mg/day with no further adverse events, and he had maintained PR at last follow-up (month 9 on ibrutinib). © 2016 by The American Society of Hematology. All rights reserved.

  13. sin 2 θ eff lept and M W(indirect) extracted from 9 fb -1 μ +μ - event sample at CDF

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

    Bodek, A.

    2016-05-31

    Here, we report on the extraction ofmore » $$\\sin^2\\theta^{\\rm lept}_{\\rm eff}$$ and indirect measurement of the mass of the W boson from the forward-backward asymmetry of $$\\mu^+\\mu^-$$ events in the $Z$ boson mass region. The data sample collected by the CDF detector corresponds to the full 9 fb$$^{-1}$$ run II sample. We measure $$\\sin^2 \\theta^{\\rm lept}_{\\rm eff} = 0.2315 \\pm 0.0010$$, $$ \\sin^2 \\theta_W = 0.2233 \\pm 0.0009$$ and $$M_W ({\\rm indirect}) = 80.365 \\pm 0.047 \\;{\\rm GeV}/c^2$$, where each uncertainty includes both statistical and systematic contributions. Comparison with the results of the D0 collaboration are presented.« less

  14. Probing the Electronic Structure of - and Electron-Doped High-Temperature Superconductors with Photoemission and X-Ray Absorption Spectroscopies

    NASA Astrophysics Data System (ADS)

    Lederman, Eli R.

    1990-01-01

    The electronic structures of hole- and electron -doped high temperature superconductors have been probed using x-ray absorption near-edge spectroscopy (XANES) and photoelectron emission spectroscopy (PES). These measurements have been performed on RBa_2Cu _3O_{rm 7-y} , La_{rm 2-x}Sr _{rm x}CuO _4 and Ln_{rm 2 -x}Ce_{rm x} CuO_{rm 4} for R = Y, Eu and Ln = Nd, Pr and Sm. The parameters x and y have been varied to include a range of hole and electron carrier densities and the undoped parent compounds. Previous XANES and PES results have indicated that unoccupied states of O 2p character can be associated with the carriers in the materials RBa_2 Cu_3O_{ rm 7-y} and La_{ rm 2-x}Sr_{rm x}CuO_4 and that the density of holes increases with O and Sr content, respectively. Conduction was hole-based in all known high-T_{ rm c} cuprates until the recent discovery of superconductivity in Ln_{rm 2-x}Ce_{rm x} CuO_4. Hall coefficient measurements have suggested that the carriers in this system are electrons added with Ce doping. It has been anticipated that these electron-doped materials will provide an important test for models of high temperature superconductivity. PES measurements are presented that show significant Cu 3d character in the valence band of these electron-based materials, but that the Cu^{2+} /Cu^{1+} ratio is unchanged by the level of Ce doping, indicating that doped electrons are itinerant rather than highly correlated. Resonant photoemission from the valence band indicates the presence of unoccupied O 2p states, but these holes are less abundant than in the hole-doped materials. Measurements of XANES at the O 1s edge suggest that unoccupied states of O 2p character in the electron -doped materials are not related to conduction in a simple way. The density of these holes is shown to decrease upon Ce doping and the process of reduction, despite the fact that both are necessary of superconductivity. Furthermore, whereas the O 2p holes are at E_{rm F} in the hole-doped materials, they are ~1 eV above E_{ rm F} in their electron-doped counterparts. A schematic of the band structure is proposed on the basis of these spectroscopic measurements.

  15. A Infrared Absorption Study of Dopant-Hydrogen Complexes in Semiconductors

    NASA Astrophysics Data System (ADS)

    Kozuch, David Michael

    1992-01-01

    Hydrogen passivation of shallow electrical dopants in semiconductors has been investigated. In particular, the passivation of the shallow dopants tin, carbon, and silicon in gallium arsenide has been studied via Fourier transform infrared spectroscopy, thermal annealing, Hall effect, secondary ion mass spectroscopy, and uniaxial stress. The bond-stretching and bond-wagging vibrational modes of the rm Sn_{Ga} - H complex in GaAs have been identified at 1327.8 cm^{-1} and 967.7 cm ^{-1}, respectively. The presence of hydrogen in the defect pair is confirmed by the deuterium -shifted bond-stretching signal at 746.6 cm^ {-1}. Infrared and Hall data correlated the passivation of Sn_{rm Ga } donors with the formation of the rm Sn_{Ga} - H complexes. A series of isochronal anneals probed the thermal stability of the complex. Arguments supporting an antibonding configuration for the rm Sn_{Ga} - H complex are presented. Infrared measurements on highly carbon doped epi -layers reveal new absorption signals at 2643, 2651, and 2688 cm^{-1} in addition to the previously identified rm C_ {As} - H stretching vibration at 2636 cm^{-1}. These new signals are related to a family of carbon-hydrogen complexes: rm C_{x} - H. Deuterium -shifted counterparts for all these signals have been observed for the first time. Sources of hydrogen have been traced to the metalorganic precursors and carrier gas used during epi-layer growth. Hydrogen-containing annealing ambients were surprisingly effective for introducing hydrogen into the epi-layers. Several atomic arrangements for the new rm C_{x} - H complexes have been considered with the most likely candidate being a rm C_{As} - H complex perturbed by another C_{rm As} acceptor in a second nearest neighbor position. The first uniaxial stress measurements have been performed on the rm Si_{As} - H complex in GaAs. The stress-induced frequency shifts and the intensity ratios of the stress-split components of the 2094.45 cm^{-1} stretching frequency reveal that the complex has trigonal symmetry. Reorientation of the stress-aligned complexes occurred by thermally activated jumps of the hydrogen atom with an activation energy of E_{rm A} = 0.26 eV. The piezospectroscopic tensor of the rm Si_{As} - H complex has been determined. The similarities between the stress data for the rm Si_{As } - H complex and the well-studied B - H complex in silicon suggest a bond-centered configuration for the rm Si_{As} - H defect pair.

  16. Acceptance of Safety and Mission Success Risks

    NASA Technical Reports Server (NTRS)

    Groen, Frank

    2015-01-01

    NASA has developed an objectives based hierarchy for guiding Reliability and Maintainability (RM) activities. This presentation overviews the hierarchy and proposes to the international trilateral partners to formulate a task force to consider the elements of the NASA RM framework, as captured in the hierarchy of RM considerations, to identify commonalities and differences in the way RM is addressed by the flight projects among the partners.

  17. Complete genomic sequences of Campylobacter jejuni strains RM3196 (233.94) and RM3197 (308.95) that were isolated from patients with Guillain-Barré Syndrome

    USDA-ARS?s Scientific Manuscript database

    An infection with Campylobacter jejuni subsp. jejuni (Cjj) is a leading cause of foodborne gastroenteritis in humans and also the most prevalent infection preceding Guillain-Barré syndrome (GBS). This study describes the complete genomic sequences of Cjj HS:41 strains RM3196 (233.94) and RM3197 (308...

  18. Extensive sequencing of seven human genomes to characterize benchmark reference materials

    PubMed Central

    Zook, Justin M.; Catoe, David; McDaniel, Jennifer; Vang, Lindsay; Spies, Noah; Sidow, Arend; Weng, Ziming; Liu, Yuling; Mason, Christopher E.; Alexander, Noah; Henaff, Elizabeth; McIntyre, Alexa B.R.; Chandramohan, Dhruva; Chen, Feng; Jaeger, Erich; Moshrefi, Ali; Pham, Khoa; Stedman, William; Liang, Tiffany; Saghbini, Michael; Dzakula, Zeljko; Hastie, Alex; Cao, Han; Deikus, Gintaras; Schadt, Eric; Sebra, Robert; Bashir, Ali; Truty, Rebecca M.; Chang, Christopher C.; Gulbahce, Natali; Zhao, Keyan; Ghosh, Srinka; Hyland, Fiona; Fu, Yutao; Chaisson, Mark; Xiao, Chunlin; Trow, Jonathan; Sherry, Stephen T.; Zaranek, Alexander W.; Ball, Madeleine; Bobe, Jason; Estep, Preston; Church, George M.; Marks, Patrick; Kyriazopoulou-Panagiotopoulou, Sofia; Zheng, Grace X.Y.; Schnall-Levin, Michael; Ordonez, Heather S.; Mudivarti, Patrice A.; Giorda, Kristina; Sheng, Ying; Rypdal, Karoline Bjarnesdatter; Salit, Marc

    2016-01-01

    The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly. PMID:27271295

  19. Biofilm Formation and Disinfectant Susceptibility of Persistent and Nonpersistent Listeria monocytogenes Isolates from Gorgonzola Cheese Processing Plants.

    PubMed

    Costa, Annalisa; Bertolotti, Luigi; Brito, Luisa; Civera, Tiziana

    2016-11-01

    The aim of this study was to investigate whether the biofilm-forming ability and/or the disinfectant susceptibility accounted for the persistence of Listeria monocytogenes in Gorgonzola cheese processing plants. For this purpose, a set of 16 L. monocytogenes isolates collected in the 2004-2007 period was analyzed, including 11 persistent isolates collected in different years, within the collection period, and displaying identical or highly correlated pulsotypes. The evaluation of biofilm-forming ability was assessed using crystal violet (CV) staining and the enumeration of viable cells on stainless steel coupons (SSC). Absorbance values obtained with CV staining for persistent and nonpersistent isolates were not significantly different (rm-ANOVA p > 0.05) and the cell counts from nonpersistent isolates showed to be higher compared with persistent isolates (rm-ANOVA p < 0.05). A simulation of disinfectant treatments was performed on spot inoculated coupons in clean and dirty conditions, according to EN 13697, and on biofilms on SSC, grown in nutrient-rich (dirty) and limiting (clean) conditions using acid acetic-hydrogen peroxide (P3) and acid citric-hydrogen peroxide (MS) commercial disinfectants. The treatment was considered effective when a 4 Log reduction in viable cell count was observed. The Log reductions of persistent and nonpersistent isolates, obtained with both the assays in clean and dirty conditions, were compared and no significant differences were detected (rm-ANOVA p > 0.05). A greater influence of organic matter on MS could explain why P3 was efficient in reducing to effective levels the majority of the isolates at the lowest concentration suggested by the manufacturer (0.2% [v/v]), while the same purpose required a higher concentration (1% [v/v]) of MS. In conclusion, our results demonstrate that the persistence of these isolates in Gorgonzola cheese processing plants was linked neither to the biofilm-forming ability nor to their susceptibility to hydrogen peroxide-based disinfectants; therefore, other factors should contribute to the persistent colonization of the dairies.

  20. The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell (ILC2) activation

    PubMed Central

    Toki, Shinji; Goleniewska, Kasia; Reiss, Sara; Zhou, Weisong; Newcomb, Dawn C; Bloodworth, Melissa H; Stier, Matthew T; Boyd, Kelli L; Polosukhin, Vasiliy V; Subramaniam, Sriram; Peebles, R Stokes

    2016-01-01

    Background Group 2 innate lymphoid cells (ILC2) are an important source of the type 2 cytokines interleukin (IL)-5 and IL-13 that are critical to the allergic airway phenotype. Previous studies reported that histone deacetylase (HDAC) inhibition by trichostatin A (TSA) downregulated adaptive allergic immune responses; however, the effect of HDAC inhibition on the early innate allergic immune response is unknown. Therefore, we investigated the effect of TSA on innate airway inflammation mediated by ILC2 activation. Methods BALB/c mice were challenged intranasally with Alternaria extract, exogenous recombinant mouse IL-33 (rmIL-33) or the respective vehicles for four consecutive days following TSA or vehicle treatment. Bronchoalveolar lavage (BAL) fluids and lungs were harvested 24 h after the last challenge. Results We found that TSA treatment significantly decreased the number of ILC2 expressing IL-5 and IL-13 in the lungs challenged with Alternaria extract or rmIL-33 compared with vehicle treatment (p<0.05). TSA treatment significantly decreased protein expression of IL-5, IL-13, CCL11 and CCL24 in the lung homogenates from Alternaria extract-challenged mice or rmIL-33-challenged mice compared with vehicle treatment (p<0.05). Further, TSA treatment significantly decreased the number of perivascular eosinophils and mucus production in the large airways that are critical components of the asthma phenotype (p<0.05). TSA did not change early IL-33 release in the BAL fluids; however, TSA decreased lung IL-33 expression from epithelial cells 24 h after last Alternaria extract challenge compared with vehicle treatment (p<0.05). Conclusions These results reveal that TSA reduces allergen-induced ILC2 activation and the early innate immune responses to an inhaled protease-containing aeroallergen. PMID:27071418

  1. Test-Retest Reliability of Rating of Perceived Exertion and Agreement With 1-Repetition Maximum in Adults.

    PubMed

    Bove, Allyn M; Lynch, Andrew D; DePaul, Samantha M; Terhorst, Lauren; Irrgang, James J; Fitzgerald, G Kelley

    2016-09-01

    Study Design Clinical measurement. Background It has been suggested that rating of perceived exertion (RPE) may be a useful alternative to 1-repetition maximum (1RM) to determine proper resistance exercise dosage. However, the test-retest reliability of RPE for resistance exercise has not been determined. Additionally, prior research regarding the relationship between 1RM and RPE is conflicting. Objectives The purpose of this study was to (1) determine test-retest reliability of RPE related to resistance exercise and (2) assess agreement between percentages of 1RM and RPE during quadriceps resistance exercise. Methods A sample of participants with and without knee pathology completed a series of knee extension exercises and rated the perceived difficulty of each exercise on a 0-to-10 RPE scale, then repeated the procedure 1 to 2 weeks later for test-retest reliability. To determine agreement between RPE and 1RM, participants completed knee extension exercises at various percentages of their 1RM (10% to 130% of predicted 1RM) and rated the perceived difficulty of each exercise on a 0-to-10 RPE scale. Percent agreement was calculated between the 1RM and RPE at each resistance interval. Results The intraclass correlation coefficient indicated excellent test-retest reliability of RPE for quadriceps resistance exercises (intraclass correlation coefficient = 0.895; 95% confidence interval: 0.866, 0.918). Overall percent agreement between RPE and 1RM was 60%, but agreement was poor within the ranges that would typically be used for training (50% 1RM for muscle endurance, 70% 1RM and greater for strength). Conclusion Test-retest reliability of perceived exertion during quadriceps resistance exercise was excellent. However, agreement between the RPE and 1RM was poor, especially in common training zones for knee extensor strengthening. J Orthop Sports Phys Ther 2016;46(9):768-774. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6498.

  2. Analysis of factors that influence the maximum number of repetitions in two upper-body resistance exercises: curl biceps and bench press.

    PubMed

    Iglesias, Eliseo; Boullosa, Daniel A; Dopico, Xurxo; Carballeira, Eduardo

    2010-06-01

    The purpose of this study was to analyze the influence of exercise type, set configuration, and relative intensity load on relationship between 1 repetition maximum (1RM) and maximum number of repetitions (MNR). Thirteen male subjects, experienced in resistance training, were tested in bench press and biceps curl for 1RM, MNR at 90% of 1RM with cluster set configuration (rest of 30s between repetitions) and MNR at 70% of 1RM with traditional set configuration (no rest between repetitions). A lineal encoder was used for measuring displacement of load. Analysis of variance analysis revealed a significant effect of load (p<0.01) and a tendency in exercise factor (p=0.096), whereas the interaction effect was not significant. MNR at 70% of 1RM was lower for biceps curl (16.31+/-2.59 vs. 8.77+/-3 in bench press and biceps curl, respectively; p<0.05) and at 90% of 1RM (21.85+/-11.06 vs. 18.54+/-12.84 in bench press and biceps curl, respectively; p>0.05). Correlation between 1RM and MNR was significant for medium-intensity in biceps curl (r=-0.574; p<0.05) and between MNR and 1RM/body mass (r=-0.574; p<0.05). Neither 1RM nor 1RM/body mass correlated with velocity along set, so velocity seems to be similar at a same relative intensity for subjects with differences in maximum strength levels. From our results, we suggest the employment of MNR rather than % of 1RM for training monitoring. Furthermore, we suggest the introduction of cluster set configuration for upper-body assessment of MNR and for upper-body muscular endurance training at high-intensity loads, as it seems an efficient approach in looking for sessions with greater training volumes. This could be an interesting approach for such sports as wrestling or weightlifting.

  3. The Relationship Between Level of Adherence to Automatic Wireless Remote Monitoring and Survival in Pacemaker and Defibrillator Patients.

    PubMed

    Varma, Niraj; Piccini, Jonathan P; Snell, Jeffery; Fischer, Avi; Dalal, Nirav; Mittal, Suneet

    2015-06-23

    Remote monitoring (RM) technology embedded within cardiac rhythm devices permits continuous monitoring, which may result in improved patient outcomes. This study used "big data" to assess whether RM is associated with improved survival and whether this is influenced by the type of cardiac device and/or its degree of use. We studied 269,471 consecutive U.S. patients implanted between 2008 and 2011 with pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), or cardiac resynchronization therapy (CRT) with pacing capability (CRT-P)/defibrillation capability (CRT-D) with wireless RM. We analyzed weekly use and all-cause survival for each device type by the percentage of time in RM (%TRM) stratified by age. Socioeconomic influences on %TRM were assessed using 8 census variables from 2012. The group had implanted PMs (n = 115,076; 43%), ICDs (n = 85,014; 32%), CRT-D (n = 61,475; 23%), and CRT-P (n = 7,906; 3%). When considered together, 127,706 patients (47%) used RM, of whom 67,920 (53%) had ≥75%TRM (high %TRM) and 59,786 (47%) <75%TRM (low %TRM); 141,765 (53%) never used RM (RM None). RM use was not affected by age or sex, but demonstrated wide geographic and socioeconomic variability. Survival was better in high %TRM versus RM None (hazard ratio [HR]: 2.10; p < 0.001), in high %TRM versus low %TRM (HR: 1.32; p < 0.001), and also in low %TRM versus RM None (HR: 1.58; p < 0.001). The same relationship was observed when assessed by individual device type. RM is associated with improved survival, irrespective of device type (including PMs), but demonstrates a graded relationship with the level of adherence. The results support the increased application of RM to improve patient outcomes. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Improved survival in patients enrolled promptly into remote monitoring following cardiac implantable electronic device implantation.

    PubMed

    Mittal, Suneet; Piccini, Jonathan P; Snell, Jeff; Prillinger, Julie B; Dalal, Nirav; Varma, Niraj

    2016-08-01

    Guidelines advocate remote monitoring (RM) in patients with a cardiac implantable electronic device (CIED). However, it is not known when RM should be initiated. We hypothesized that prompt initiation of RM (within 91 days of implant) is associated with improved survival compared to delayed initiation. This retrospective, national, observational cohort study evaluated patients receiving new implants of market-released St. Jude Medical™ pacemakers (PM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices. Patients were assigned to one of two groups: an "RM Prompt" group, in which RM was initiated within 91 days of implant; and an "RM Delayed" group, in which RM was initiated >91 days but ≤365 days of implant. The primary endpoint was all-cause mortality. The cohort included 106,027 patients followed for a mean of 2.6 ± 0.9 years. Overall, 47,014 (44 %) patients had a PM, 31,889 (30 %) patients had an ICD, 24,005 (23 %) patients had a CRT-D, and 3119 (3 %) patients had a CRT-P. Remote monitoring was initiated promptly (median 4 weeks [IQR 2, 8 weeks]) in 66,070 (62 %) patients; in the other 39,957 (38 %) patients, RM initiation was delayed (median 24 weeks [IQR 18, 34 weeks]). In comparison to delayed initiation, prompt initiation of RM was associated with a lower mortality rate (4023 vs. 4679 per 100,000 patient-years, p < 0.001) and greater adjusted survival (HR 1.18 [95 % CI 1.13-1.22], p < 0.001). Our data, for the first time, show improved survival in patients enrolled promptly into RM following CIED implantation. This advantage was observed across all CIED device types.

  5. The Association between Maximal Bench Press Strength and Isometric Handgrip Strength among Breast Cancer Survivors

    PubMed Central

    Rogers, Benjamin H.; Brown, Justin C.; Gater, David R.; Schmitz, Kathryn H.

    2016-01-01

    Objective One-repetition maximum (1-RM) bench press strength is considered the gold standard to quantify upper-body muscular strength. Isometric handgrip strength is frequently used as a surrogate for 1-RM bench press strength among breast cancer (BrCa) survivors. The relationship between 1-RM bench press strength and isometric handgrip strength, however, has not been characterized among BrCa survivors. Design Cross-sectional study. Setting Laboratory. Participants Community-dwelling BrCa survivors. Interventions Not applicable. Main Outcome Measure 1-RM bench press strength was measured with a barbell and exercise bench. Isometric handgrip strength was measured using an isometric dynamometer with three maximal contractions of left and right hands. All measures were conducted by staff with training in clinical exercise testing. Results Among 295 BrCa survivors, 1-RM bench press strength was 18.2±6.1 kg (range: 2.2-43.0) and isometric handgrip strength was 23.5±5.8 kg (range: 9.0-43.0). The strongest correlate of 1-RM bench press strength was the average isometric handgrip strength of both hands (r=0.399; P<0.0001). Mean-difference analysis suggested that the average isometric handgrip strength of both hands overestimated 1-RM bench press strength by 4.7 kg (95% limits of agreement: −8.2 to 17.6). In a multivariable linear regression model, the average isometric handgrip strength of both hands (β=0.31; P<0.0001) and age (β=−0.20; P<0.0001) were positively correlated with 1-RM bench press strength (R2=0.23). Conclusions Isometric handgrip strength is a poor surrogate for 1-RM bench press strength among BrCa survivors. 1-RM bench press and isometric handgrip strength quantify distinct components of muscular strength. PMID:27543047

  6. Biological reference materials for extracellular vesicle studies.

    PubMed

    Valkonen, S; van der Pol, E; Böing, A; Yuana, Y; Yliperttula, M; Nieuwland, R; Laitinen, S; Siljander, P R M

    2017-02-15

    Extracellular vesicles (EVs) mediate normal physiological homeostasis and pathological processes by facilitating intercellular communication. Research of EVs in basic science and clinical settings requires both methodological standardization and development of reference materials (RM). Here, we show insights and results of biological RM development for EV studies. We used a three-step approach to find and develop a biological RM. First, a literature search was done to find candidates for biological RMs. Second, a questionnaire was sent to EV researchers querying the preferences for RM and their use. Third, a biological RM was selected, developed, characterized, and evaluated. The responses to the survey demonstrated a clear and recognized need for RM optimized for the calibration of EV measurements. Based on the literature, naturally occurring and produced biological RM, such as virus particles and liposomes, were proposed as RM. However, none of these candidate RMs have properties completely matching those of EVs, such as size and refractive index distribution. Therefore, we evaluated the use of nanoerythrosomes (NanoE), vesicles produced from erythrocytes, as a potential biological RM. The strength of NanoE is their resemblance to EVs. Compared to the erythrocyte-derived EVs (eryEVs), NanoE have similar morphology, a similar refractive index (1.37), larger diameter (70% of the NanoE are over 200nm), and increased positive staining for CD235a and lipids (Di-8-ANEPPS) (58% and 67% in NanoE vs. 21% and 45% in eryEVs, respectively). Altogether, our results highlight the general need to develop and validate new RM with similar physical and biochemical properties as EVs to standardize EV measurements between instruments and laboratories. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Metabolic and Structural Imaging at 7 Tesla After Repetitive Mild Traumatic Brain Injury in Immature Rats.

    PubMed

    Fidan, Emin; Foley, Lesley M; New, Lee Ann; Alexander, Henry; Kochanek, Patrick M; Hitchens, T Kevin; Bayır, Hülya

    2018-01-01

    Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes using diffusion tensor imaging of the whole brain and proton magnetic resonance spectroscopy of the hippocampi at 7 Tesla in 18-day-old male rats at 7 days after mTBI and rmTBI. Traumatic axonal injury was assessed by beta-amyloid precursor protein accumulation using immunohistochemistry. A significant decrease in fractional anisotropy and increase in axial and radial diffusivity were observed in several brain regions, especially in white matter regions, after a single mTBI versus sham and more prominently after rmTBI. In addition, we observed accumulation of beta-amyloid precursor protein in the external capsule after mTBI and rmTBI. mTBI and rmTBI reduced the N-acetylaspartate/creatine ratio (NAA/Cr) and increased the myoinositol/creatine ratio (Ins/Cr) versus sham. rmTBI exacerbated the reduction in NAA/Cr versus mTBI. The choline/creatine (Cho/Cr) and (lipid/Macro Molecule 1)/creatine (Lip/Cr) ratios were also decreased after rmTBI versus sham. Diffusion tensor imaging findings along with the decrease in Cho and Lip after rmTBI may reflect damage to axonal membrane. NAA and Ins are altered at 7 days after mTBI and rmTBI likely reflecting neuro-axonal damage and glial response, respectively. These findings may be relevant to understanding the extent of disability following mTBI and rmTBI in the immature brain and may identify possible therapeutic targets.

  8. The Cost and Utility of Renal Transplantation in Malaysia

    PubMed Central

    Bavanandan, Sunita; Yap, Yok-Chin; Ahmad, Ghazali; Wong, Hin-Seng; Azmi, Soraya; Goh, Adrian

    2015-01-01

    Background Kidney transplantation is the optimal therapy for the majority of patients with end-stage renal disease. However, the cost and health outcomes of transplantation have not been assessed in a middle-income nation with a low volume of transplantation, such as Malaysia. Aim and Methods This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death. Results Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively. Conclusions Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life. PMID:27500211

  9. Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases.

    PubMed

    Choi, Tae Yeong; Lee, Hye Min; Park, Won Kyoung; Jeong, So Yeong; Moon, Hwa Sook

    2014-11-01

    The purpose of this study was to determine the frequency and distribution of cytogenetically abnormal miscarriages in couples with spontaneous abortions (SA) or recurrent miscarriages (RM). Karyotyping of specimens from 164 abortuses with SA and 86 abortuses with RM was successfully performed according to the standard cytogenetic methods using G-banding technique. Among the total 164 cases of SA group, 81 (49.4%) were euploid and the rest (83, 50.6%) showed chromosomal abnormalities. In RM(≥2) and RM(≥3) group, 31 (36.0%)/27 (34.6%) cases were euploid and 55 (64.0%)/51(65.4%) cases were abnormal, respectively. A statistically significant difference was found in the rate of cytogenetic abnormality between SA and RM groups (P<0.05). In all groups, women with advanced maternal age (≥35 years) had a higher rate of chromosome anomalies compared with women younger than age 35 (normal:abnormal = 32.4%:67.6% for ≥35 years and 53.8%:46.2% for <35 years in SA; 19.2%:80.8%/21.7%:78.3% for ≥35 years and 43.3%:56.7%/40.0%:60.0% for <35 years in RM(≥2) and RM(≥3), respectively; P<0.05). In SA group, an increase of normal karyotypes was noted with increased gestational age (<10 week, 38.0%; 10-15 week, 53.5%; 16-20 week, 65.7%). In RM group, most of cases were in <10 week and the frequency of trisomies with chromosomes 1 to 10 were increased compared with that of SA. There was a statistically significant difference in the frequency and distribution of chromosomal abnormalities between SA and RM groups. Our results will provide useful information for diagnosis and genetic counseling of patients with SA or RM.

  10. An examination of the predictive validity of the risk matrix 2000 in England and wales.

    PubMed

    Barnett, Georgia D; Wakeling, Helen C; Howard, Philip D

    2010-12-01

    This study examined the predictive validity of an actuarial risk-assessment tool with convicted sexual offenders in England and Wales. A modified version of the RM2000/s scale and the RM2000 v and c scales (Thornton et al., 2003) were examined for accuracy in predicting proven sexual violent, nonsexual violent, and combined sexual and/or nonsexual violent reoffending in a sample of sexual offenders who had either started a community sentence or been released from prison into the community by March 2007. Rates of proven reoffending were examined at 2 years for the majority of the sample (n = 4,946), and 4 years ( n = 578) for those for whom these data were available. The predictive validity of the RM2000 scales was also explored for different subgroups of sexual offenders to assess the robustness of the tool. Both the modified RM2000/s and the complete v and c scales effectively classified offenders into distinct risk categories that differed significantly in rates of proven sexual and/or nonsexual violent reoffending. Survival analyses on the RM2000/s and v scales (N = 9,284) indicated that the higher risk groups offended more quickly and at a higher rate than lower risk groups. The relative predictive validity of the RM2000/s, v, and c, as calculated using Receiver Operating Characteristics (ROC) analyses, were moderate (.68) for RM2000/s and large for both the RM2000/c (.73) and RM2000/v (.80), at the 2-year follow-up. RM2000/s was moderately accurate in predicting relative risk of proven sexual reoffending for a variety of subgroups of sexual offenders.

  11. Effects of Badminton Expertise on Representational Momentum: A Combination of Cross-Sectional and Longitudinal Studies

    PubMed Central

    Jin, Hua; Wang, Pin; Fang, Zhuo; Di, Xin; Ye, Zhuo’er; Xu, Guiping; Lin, Huiyan; Cheng, Yongmin; Li, Yongjie; Xu, Yong; Rao, Hengyi

    2017-01-01

    Representational momentum (RM) has been found to be magnified in experts (e.g., sport players) with respect to both real and implied motion in expert-familiar domains. However, it remains unclear whether similar effects can be achieved in expert-unfamiliar domains, especially within the context of implied motion. To answer this question, we conducted two independent experiments using an implied motion paradigm and examined the expert effects of badminton training on RM in both adult and child players. In Experiment 1, we used a cross-sectional design and compared RM between adult professional badminton players and matched controls. The results revealed significantly enhanced RM for adult players, supporting the expert effect in expert-unfamiliar domains for implied motion. However, cross-sectional studies could not ascertain whether the observed expert effect was due to innate factors or expertise acquirement. Therefore, in Experiment 2, we used a longitudinal design and compared RM between two groups of child participants, naming child players who had enrolled professional badminton training program at a sports school and age-matched peer non-players who attended an ordinary primary school without sports training. Before training, there were no differences in RM among child players, their non-player peers, and adult non-players. However, after 4 years of badminton training, child players demonstrated significantly enhanced RM compared to themselves prior to training. The increased RM observed in both adult and child players suggests that badminton expertise modulates implied motion RM. PMID:28970810

  12. Predicting the Size and Timing of Sunspot Maximum for Cycle 24

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.

    2010-01-01

    For cycle 24, the minimum value of the 12-month moving average (12-mma) of the AA-geomagnetic index in the vicinity of sunspot minimum (AAm) appears to have occurred in September 2009, measuring about 8.4 nT and following sunspot minimum by 9 months. This is the lowest value of AAm ever recorded, falling below that of 8.9 nT, previously attributed to cycle 14, which also is the smallest maximum amplitude (RM) cycle of the modern era (RM = 64.2). Based on the method of Ohl (the preferential association between RM and AAm for an ongoing cycle), one expects cycle 24 to have RM = 55+/-17 (the +/-1 - sigma prediction interval). Instead, using a variation of Ohl's method, one based on using 2-cycle moving averages (2-cma), one expects cycle 23's 2-cma of RM to be about 115.5+/-8.7 (the +/-1 - sigma prediction interval), inferring an RM of about 62+/-35 for cycle 24. Hence, it seems clear that cycle 24 will be smaller in size than was seen in cycle 23 (RM = 120.8) and, likely, will be comparable in size to that of cycle 14. From the Waldmeier effect (the preferential association between the ascent duration (ASC) and RM for an ongoing cycle), one expects cycle 24 to be a slow-rising cycle (ASC > or equal to 48 months), having RM occurrence after December 2012, unless it turns out to be a statistical outlier.

  13. Bench press and push-up at comparable levels of muscle activity results in similar strength gains.

    PubMed

    Calatayud, Joaquin; Borreani, Sebastien; Colado, Juan C; Martin, Fernando; Tella, Victor; Andersen, Lars L

    2015-01-01

    Electromyography (EMG) exercise evaluation is commonly used to measure the intensity of muscle contraction. Although researchers assume that biomechanically comparable resistance exercises with similar high EMG levels will produce similar strength gains over the long term, no studies have actually corroborated this hypothesis. This study evaluated EMG levels during 6 repetition maximum (6RM) bench press and push-up, and subsequently performed a 5-week training period where subjects were randomly divided into 3 groups (i.e., 6RM bench press group, 6RM elastic band push-up group, or control group) to evaluate muscle strength gains. Thirty university students with advanced resistance training experience participated in the 2-part study. During the training period, exercises were performed using the same loads and variables that were used during the EMG data collection. At baseline, EMG amplitude showed no significant difference between 6RM bench press and band push-up. Significant differences among the groups were found for percent change (Δ) between pretest and posttest for 6RM (p = 0.017) and for 1 repetition maximum (1RM) (p < 0.001). Six repetition maximum bench press group and 6RM elastic band push-up group improved their 1RM and 6RM (Δ ranging from 13.65 to 22.21) tests significantly with similar gains, whereas control group remains unchanged. Thus, when the EMG values are comparable and the same conditions are reproduced, the aforementioned exercises can provide similar muscle strength gains.

  14. Localization of a bacterial group II intron-encoded protein in eukaryotic nuclear splicing-related cell compartments.

    PubMed

    Nisa-Martínez, Rafael; Laporte, Philippe; Jiménez-Zurdo, José Ignacio; Frugier, Florian; Crespi, Martin; Toro, Nicolás

    2013-01-01

    Some bacterial group II introns are widely used for genetic engineering in bacteria, because they can be reprogrammed to insert into the desired DNA target sites. There is considerable interest in developing this group II intron gene targeting technology for use in eukaryotes, but nuclear genomes present several obstacles to the use of this approach. The nuclear genomes of eukaryotes do not contain group II introns, but these introns are thought to have been the progenitors of nuclear spliceosomal introns. We investigated the expression and subcellular localization of the bacterial RmInt1 group II intron-encoded protein (IEP) in Arabidopsis thaliana protoplasts. Following the expression of translational fusions of the wild-type protein and several mutant variants with EGFP, the full-length IEP was found exclusively in the nucleolus, whereas the maturase domain alone targeted EGFP to nuclear speckles. The distribution of the bacterial RmInt1 IEP in plant cell protoplasts suggests that the compartmentalization of eukaryotic cells into nucleus and cytoplasm does not prevent group II introns from invading the host genome. Furthermore, the trafficking of the IEP between the nucleolus and the speckles upon maturase inactivation is consistent with the hypothesis that the spliceosomal machinery evolved from group II introns.

  15. Localization of a Bacterial Group II Intron-Encoded Protein in Eukaryotic Nuclear Splicing-Related Cell Compartments

    PubMed Central

    Nisa-Martínez, Rafael; Laporte, Philippe; Jiménez-Zurdo, José Ignacio; Frugier, Florian; Crespi, Martin; Toro, Nicolás

    2013-01-01

    Some bacterial group II introns are widely used for genetic engineering in bacteria, because they can be reprogrammed to insert into the desired DNA target sites. There is considerable interest in developing this group II intron gene targeting technology for use in eukaryotes, but nuclear genomes present several obstacles to the use of this approach. The nuclear genomes of eukaryotes do not contain group II introns, but these introns are thought to have been the progenitors of nuclear spliceosomal introns. We investigated the expression and subcellular localization of the bacterial RmInt1 group II intron-encoded protein (IEP) in Arabidopsis thaliana protoplasts. Following the expression of translational fusions of the wild-type protein and several mutant variants with EGFP, the full-length IEP was found exclusively in the nucleolus, whereas the maturase domain alone targeted EGFP to nuclear speckles. The distribution of the bacterial RmInt1 IEP in plant cell protoplasts suggests that the compartmentalization of eukaryotic cells into nucleus and cytoplasm does not prevent group II introns from invading the host genome. Furthermore, the trafficking of the IEP between the nucleolus and the speckles upon maturase inactivation is consistent with the hypothesis that the spliceosomal machinery evolved from group II introns. PMID:24391881

  16. The Effects of Mental Imagery with Video-Modeling on Self-Efficacy and Maximal Front Squat Ability

    PubMed Central

    Buck, Daniel J. M.; Hutchinson, Jasmin C.; Winter, Christa R.; Thompson, Brian A.

    2016-01-01

    This study was designed to assess the effectiveness of mental imagery supplemented with video-modeling on self-efficacy and front squat strength (three repetition maximum; 3RM). Subjects (13 male, 7 female) who had at least 6 months of front squat experience were assigned to either an experimental (n = 10) or a control (n = 10) group. Subjects′ 3RM and self-efficacy for the 3RM were measured at baseline. Following this, subjects in the experimental group followed a structured imagery protocol, incorporating video recordings of both their own 3RM performance and a model lifter with excellent technique, twice a day for three days. Subjects in the control group spent the same amount of time viewing a placebo video. Following three days with no physical training, measurements of front squat 3RM and self-efficacy for the 3RM were repeated. Subjects in the experimental group increased in self-efficacy following the intervention, and showed greater 3RM improvement than those in the control group. Self-efficacy was found to significantly mediate the relationship between imagery and front squat 3RM. These findings point to the importance of mental skills training for the enhancement of self-efficacy and front squat performance.

  17. Increased frequency of rhinitis medicamentosa due to media advertising for nasal topical decongestants.

    PubMed

    Archontaki, M; Symvoulakis, E K; Hajiioannou, J K; Stamou, A K; Kastrinakis, S; Bizaki, A J; Kyrmizakis, D E

    2009-01-01

    The aim of this study was to investigate the frequency of rhinitis medicamentosa (RM) in patients attending the ENT outpatient clinic of the General Hospital of Rethymnon (Crete, Greece) before and after the launch of an intensive nasal decongestant advertising campaign in Greece. We reviewed the medical records of the patients with RM seen at the ENT outpatient clinic in May, June and July of 2003 and 2006. We analyzed and recorded the gender, age, and related clinical information of the patients with RM. In May, June and July of 2003, 41 patients out of a total of 1780 patients attending the ENT outpatient clinic were diagnosed with RM (2.3%). In the same months in 2006, 161 patients out a total of 1898 patients were diagnosed with RM (8.5%). The frequency of RM in these groups was therefore found to have increased significantly between 2003 and 2006. In 2006, 8 out of 10 patients with RM reported that they had made their purchasing decision solely on the basis of the information supplied by the drug advertisement without consulting their doctor or pharmacist. We suggest that the intensive media advertising campaign for nasal topical decongestants (particularly on TV) which started in 2004 is probably the main reason for this "endemic" RM.

  18. Ground reaction forces and knee kinetics during single and repeated badminton lunges.

    PubMed

    Lam, Wing Kai; Ding, Rui; Qu, Yi

    2017-03-01

    Repeated movement (RM) lunge that frequently executed in badminton might be used for footwear evaluation. This study examined the influence of single movement (SM) and RM lunges on the ground reaction forces (GRFs) and knee kinetics during the braking phase of a badminton lunge step. Thirteen male university badminton players performed left-forward lunges in both SM and RM sessions. Force platform and motion capturing system were used to measure GRFs and knee kinetics variables. Paired t-test was performed to determine any significant differences between SM and RM lunges regarding mean and coefficient of variation (CV) in each variable. The kinetics results indicated that compared to SM lunges, the RM lunges had shorter contact time and generated smaller maximum loading rate of impact force, peak knee anterior-posterior force, and peak knee sagittal moment but generated larger peak horizontal resultant forces (Ps < 0.05). Additionally, the RM lunges had lower CV for peak knee medial-lateral and vertical forces (Ps < 0.05). These results suggested that the RM testing protocols had a distinct loading response and adaptation pattern during lunge and that the RM protocol showed higher within-trial reliability, which may be beneficial for the knee joint loading evaluation under different interventions.

  19. Increasing arsenic sorption on red mud by phosphogypsum addition.

    PubMed

    Lopes, G; Guilherme, L R G; Costa, E T S; Curi, N; Penha, H G V

    2013-11-15

    Mining by-products have been tested as adsorbents for arsenic in order to reduce As bioavailability. This study evaluated a red mud (RM) treated with or without phosphogypsum (G) in order to improve its As retention. Red mud and G samples and their mixtures were chemically and mineralogically characterized to gather information concerning their composition, which is key for a better understanding of the adsorbent properties. Phosphogypsum was added to RM in the following proportions: 0, 1, 2, 5, 10, and 25% by weight. These mixtures were subjected to As adsorption and desorption and tested for their maximum adsorption capacity of As (AsMAC). Arsenic adsorption increased upon increasing the proportion of G added to RM. The AsMAC at pure RM reached 909 mg kg(-1), whereas the 75%-RM+25%-G mixture sorbed up to 3333 mg kg(-1) of As, i.e., a 3.5-fold increase in AsMAC. Using G in mixtures with RM increases the efficiency of As adsorption due to the presence of Ca(2+), which alters the charge balance of the adsorbent, leading to the formation of ternary complexes. Addition of G to RM is thus a promising technique to improve As retention, while providing additional value to both by-products, G and RM. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Correlation between Resection Margin and Disease Recurrence with a Restricted Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma.

    PubMed

    Lee, Woohyung; Han, Ho-Seong; Ahn, Soyeon; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok

    2018-01-17

    The relationship between resection margin (RM) and recurrence of resected hepatocellular carcinoma (HCC) is unclear. We reviewed clinical data for 419 patients with HCC. The oncologic outcomes were compared between 2 groups of patients classified according to the inflexion point of the restricted cubic spline plot. The patients were divided according to an RM of <1 cm (n = 233; narrow RM group) or ≥1 cm (n = 186; wide RM group). The 5-year recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in the narrow RM group. Patients with multiple lesions, or prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from subgroup analyses. In patients with a 2-5 cm HCC, the 5-year RFS was greater in the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95% CI 1.029-2.976, p = 0.039) was independently associated with disease recurrence. In patients with a single 2-5 cm HCC without prior TACE/RFA, an RM of ≥1 cm was associated with lower risk of recurrence after liver resection. © 2018 S. Karger AG, Basel.

  1. Potential Renoprotective Effects of Rosemary and Thyme Against Gentamicin Toxicity in Rats.

    PubMed

    Abdel-Azeem, Amal S; Hegazy, Amany M; Zeidan, Hala M; Ibrahim, Khadiga S; El-Sayed, Eman M

    2017-07-04

    Gentamicin (GM) is a drug used commonly against gram-negative bacteria. Its therapeutic use is mainly limited by its nephrotoxicity. This investigation was aimed at evaluating the nephroprotective effects of rosemary (RM; Rosmarinus officinalis) and thyme (TV; Thymus vulgaris) against GM toxicity. Rats were divided into four groups. Normal control group was treated intraperitoneally (i.p.) with saline; positive control group was administered GM 60 mg/kg/day i.p.; RM group was co-administered 8% RM aqueous extract, 10 mL/kg/day, orally with GM; and TV group was co-administered 8% TV aqueous extract orally, 10 mL/kg/day with GM. Both RM and TV groups extracted significantly ameliorated plasma kidney function biomarkers, and reduced malondialdhyde and glucose levels. Meanwhile, RM extract significantly modulated the electrolyte concentration and increased plasma insulin levels as compared with the GM group. However, the aqueous extract of RM showed more pronounced effects than TV extract. Our data were confirmed by histopathological examination and deoxyribonucleic acid (DNA) fragmentation analysis. Deleterious histopathological changes and increased DNA fragmentation induced by GM treatment were markedly controlled by the co-administration of RM and TV. Such renoprotective influence of RM and TV suggests their concurrent supplementation with GM therapy to limit GM toxicity.

  2. The Effects of Mental Imagery with Video-Modeling on Self-Efficacy and Maximal Front Squat Ability.

    PubMed

    Buck, Daniel J M; Hutchinson, Jasmin C; Winter, Christa R; Thompson, Brian A

    2016-04-14

    This study was designed to assess the effectiveness of mental imagery supplemented with video-modeling on self-efficacy and front squat strength (three repetition maximum; 3RM). Subjects (13 male, 7 female) who had at least 6 months of front squat experience were assigned to either an experimental ( n = 10) or a control ( n = 10) group. Subjects' 3RM and self-efficacy for the 3RM were measured at baseline. Following this, subjects in the experimental group followed a structured imagery protocol, incorporating video recordings of both their own 3RM performance and a model lifter with excellent technique, twice a day for three days. Subjects in the control group spent the same amount of time viewing a placebo video. Following three days with no physical training, measurements of front squat 3RM and self-efficacy for the 3RM were repeated. Subjects in the experimental group increased in self-efficacy following the intervention, and showed greater 3RM improvement than those in the control group. Self-efficacy was found to significantly mediate the relationship between imagery and front squat 3RM. These findings point to the importance of mental skills training for the enhancement of self-efficacy and front squat performance.

  3. Phytoremediation of metals using lemongrass (Cymbopogon citratus (D.C.) Stapf.) grown under different levels of red mud in soil amended with biowastes.

    PubMed

    Gautam, Meenu; Pandey, Divya; Agrawal, Madhoolika

    2017-06-03

    Due to hostile condition of red mud (RM), its utilization for vegetation is restricted. Therefore, RM with biowastes as soil amendment may offer suitable combination to support plant growth with reduced risk of metal toxicity. To evaluate the effects of RM on soil properties, plant growth performance, and metal accumulation in lemongrass, a study was conducted using different RM concentrations (0, 5, 10, and 15% w/w) in soil amended with biowastes [cow dung manure (CD) or sewage-sludge (SS)]. Application of RM in soil with biowastes improved organic matter and nutrient contents and caused reduction in phytoavailable metal contents. Total plant biomass was increased under all treatments, maximally at 5% RM in soil with SS (91.4%) and CD (51.7%) compared to that in control (no RM and biowastes). Lemongrass acted as a potential metal-tolerant plant as its metal tolerance index is >100%. Based on translocation and bioconcentration factors, lemongrass acted as a potential phytostabilizer of Fe, Mn, and Cu in roots and was found efficient in translocation of Al, Zn, Cd, Pb, Cr, As, and Ni from roots to shoot. The study suggests that 5% RM with biowastes preferably SS may be used to enhance phytoremediation potential of lemongrass.

  4. Enhancing DNA electro-transformation efficiency on a clinical Staphylococcus capitis isolate.

    PubMed

    Cui, Bintao; Smooker, Peter M; Rouch, Duncan A; Deighton, Margaret A

    2015-02-01

    Clinical staphylococcus isolates possess a stronger restriction-modification (RM) barrier than laboratory strains. Clinical isolates are therefore more resistant to acceptance of foreign genetic material than laboratory strains, as their restriction systems more readily recognize and destroy foreign DNA. This stronger barrier consequently restricts genetic studies to a small number of domestic strains that are capable of accepting foreign DNA. In this study, an isolate of Staphylococcus capitis, obtained from the blood of a very low birth-weight baby, was transformed with a shuttle vector, pBT2. Optimal conditions for electro-transformation were as follows: cells were harvested at mid-log phase, electro-competent cells were prepared; cells were pre-treated at 55°C for 1min; 3μg of plasmid DNA was mixed with 70-80μL of competent cells (3-4×10(10)cells/mL) at 20°C in 0.5M sucrose, 10% glycerol; and electroporation was conducted using 2.1kV/cm field strength with a 0.1cm gap. Compared to the conventional method, which involves DNA electroporation of Staphylococcus aureus RN4220 as an intermediate strain to overcome the restriction barrier, our proposed approach exhibits a higher level (3 log10 units) of transformation efficiency. Heat treatment was used to temporarily inactivate the recipient RM barrier. Other important parameters contributing to improved electro-transformation efficiency were growth stage for cell harvesting, the quantity of DNA, the transformation temperature and field strength. The approach described here may facilitate genetic manipulations of this opportunistic pathogen. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Remote monitoring for active cardiovascular implantable electronic devices: a European survey.

    PubMed

    Halimi, Franck; Cantù, Francesco

    2010-12-01

    This survey sampled today's European practices in the use of remote monitoring (RM) for the follow-up of active cardiovascular implantable electronic devices. Eighty-five per cent of the responding centres are currently using RM. For the majority, RM is expected to increase importantly within 5 years, and it has already led to a new organization of care based on dedicated allied professionals and/or the creation of RM units. There are still major limitations for the development of RM, such as ethical and legal aspects, reimbursement issues, and the lack of specific national- and European-updated guidelines which need to be informed.

  6. Atomic-Scale Structure of the Tin DX Center and Other Related Defects in Aluminum Gallium Arsenide Semiconductors Using Moessbauer Spectroscopy.

    NASA Astrophysics Data System (ADS)

    Greco, Luigi Alessandro

    The DX center in III-V alloys has limited the use of these materials for electronic devices since the defect acts as an electron trap. To be able to control or eliminate the DX center, its atomic scale structure should be understood. Mossbauer spectroscopy has proven to be a valuable technique in probing the atomic-scale structure of certain atomic species. The dopant studied here is ^{119}Sn. The thermal diffusion of Sn in Al_ {rm x}Ga_{rm 1-x }As using different temperatures, times, sample geometries and As_4 overpressures in evacuated and sealed fused silica ampoules was studied by x-ray diffraction (XRD), secondary ion mass spectroscopy and electrochemical capacitance versus voltage measurements. The AlGaAs surfaces decomposed into various Sn, Si, Ga and As oxides when an As_4 overpressure was introduced during annealing. However, annealing under ambient As_4 and furnace cooling eliminated surface decomposition although the Sn diffusion depth was less than that for a 0.5 atm As_4 overpressure. SiO_{rm x} and Si_{rm x }N_{rm y} RF-sputtered thin film capping layers deposited on AlGaAs were studied by XRD and Auger electron spectroscopy. For the annealed SiO_{rm x} films the AlGaAs surface was preserved, independent of the cooling technique used. Mossbauer spectroscopy was conducted on ^{rm 119m} Sn-implanted Al_ {rm x } Ga_{rm 1-x} As (x = 0.22 and 0.25) used for the source experiments and ^{119}Sn-doped Al _{rm x}Ga _{rm 1-x}As (x = 0.15, N _{rm Sn} ~2 times 10 ^{18} cm^{ -3}) for the absorber experiment. The source samples were capped with 120 nm of SiO_ {rm x} to preserve the surface during the systematic study of annealing temperature versus site occupation and electrical activation via Mossbauer spectroscopy at 76 K and 4 K in the dark and in the light (to observe persistent photoconductivity (PPC) due to the DX center). For all of the annealing conditions used the x = 0.22 sample showed little evidence of PPC possibly due to compensating defects and/or radiation-induced capture. After annealing the x = 0.25 sample at 1000^circC for 2 hours under a Ga + Al overpressure, evidence of PPC was found via Hall measurements but no effect was seen by Mossbauer suggesting radiation-induced capture and/or non-nearest-neighbor lattice relaxation. The Ga + Al overpressure also served to decrease the loss of Sn through the SiO _{rm x} film, possibly through the removal of Ga and Al vacancies. The x = 0.15 absorber showed a persistent 15-18% change in the electrical resistance (10% change in n) between the light and dark. However, the observation of this effect was not apparent, even assuming negative-U (2 electron) behavior, in the Mossbauer measurements. This was also consistent with EXAFS results. These studies do not support the broken-bond model of Chadi and Chang, which is considered to be a widely accepted atomic-scale model of the DX center. A defect complex consisting of a substitutional Sn_{rm Ga(Al) }^+ site, and a (V_{ rm III}^-Al_{ rm As}^{-2}) complex, which localizes 3 electrons and may not be a nearest-neighbor to the donor, was chosen for the DX center in the x = 0.15 sample which supports EXAFS, recent positron annihilation and these Mossbauer studies.

  7. CD-SEM real time bias correction using reference metrology based modeling

    NASA Astrophysics Data System (ADS)

    Ukraintsev, V.; Banke, W.; Zagorodnev, G.; Archie, C.; Rana, N.; Pavlovsky, V.; Smirnov, V.; Briginas, I.; Katnani, A.; Vaid, A.

    2018-03-01

    Accuracy of patterning impacts yield, IC performance and technology time to market. Accuracy of patterning relies on optical proximity correction (OPC) models built using CD-SEM inputs and intra die critical dimension (CD) control based on CD-SEM. Sub-nanometer measurement uncertainty (MU) of CD-SEM is required for current technologies. Reported design and process related bias variation of CD-SEM is in the range of several nanometers. Reference metrology and numerical modeling are used to correct SEM. Both methods are slow to be used for real time bias correction. We report on real time CD-SEM bias correction using empirical models based on reference metrology (RM) data. Significant amount of currently untapped information (sidewall angle, corner rounding, etc.) is obtainable from SEM waveforms. Using additional RM information provided for specific technology (design rules, materials, processes) CD extraction algorithms can be pre-built and then used in real time for accurate CD extraction from regular CD-SEM images. The art and challenge of SEM modeling is in finding robust correlation between SEM waveform features and bias of CD-SEM as well as in minimizing RM inputs needed to create accurate (within the design and process space) model. The new approach was applied to improve CD-SEM accuracy of 45 nm GATE and 32 nm MET1 OPC 1D models. In both cases MU of the state of the art CD-SEM has been improved by 3x and reduced to a nanometer level. Similar approach can be applied to 2D (end of line, contours, etc.) and 3D (sidewall angle, corner rounding, etc.) cases.

  8. Absence of Fast-Moving Iron in an Intermediate Type Ia Supernova Between Normal and Super-Chandrasekhar

    DOE PAGES

    Cao, Yi; Johansson, J.; Nugent, Peter E.; ...

    2016-06-01

    In this study, we report observations of a peculiar SN Ia iPTF13asv (a.k.a., SN2013cv) from the onset of the explosion to months after its peak. The early-phase spectra of iPTF13asv show an absence of iron absorption, indicating that synthesized iron elements are confined to low-velocity regions of the ejecta, which, in turn, implies a stratified ejecta structure along the line of sight. Our analysis of iPTF13asv's light curves and spectra shows that it is an intermediate case between normal and super-Chandrasekhar events. On the one hand, its light curve shape (B-bandmore » $${\\rm{\\Delta }}{m}_{15}=1.03\\pm 0.01$$) and overall spectral features resemble those of normal SNe Ia. On the other hand, its large peak optical and UV luminosity ($${M}_{B}=-19.84\\;{\\rm{mag}}$$, $${M}_{{uvm}2}=-15.5\\;{\\rm{mag}}$$) and its low but almost constant Si ii velocities of about 10,000 km s -1 are similar to those in super-Chandrasekhar events, and its persistent carbon signatures in the spectra are weaker than those seen commonly in super-Chandrasekhar events. We estimate a 56Ni mass of $${0.81}_{-0.18}^{+0.10}{M}_{\\odot }$$ and a total ejecta mass of $${1.59}_{-0.12}^{+0.45}{M}_{\\odot }$$. Finally, the large ejecta mass of iPTF13asv and its stratified ejecta structure together seemingly favor a double-degenerate origin.« less

  9. The Mechanisms and Effects of the Plant Activation of Chemicals in the Environment

    DTIC Science & Technology

    1991-12-02

    amino- Uilich et al., 1973; Raz- fluorene-N-hydroxylase. zouk et al., 1980 * Did not inhibit the TXI cell activation of m-PDA, howev- Wagner et al...P450 in mammals and Goujon et al., 1972, Car- yeast. Inhibited 2-AF hydroxylase. ratore et al., 1986; Raz- zouk et al., 1980 i Did not inhibit the TXI...Activation of 2-aminofluorene by cultured plant cells. Science 219:1427-1429 Poulsen LL, R.M. Hyslop , D.M. Ziegler. 1974. S-oxidation of

  10. Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as Novel Therapeutic Targets

    DTIC Science & Technology

    2015-10-01

    Michkov AV, Lynch RM, Overland AC, Corriden R. G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic...M. Chinn, Alexander V. Michkov, Rebecca M. Lynch , Aaron C. Overland, and Ross Corriden Departments of Pharmacology (P.A.I., A.W., A.C.Z., A.N.S., N.A...Sriram, Chinn, Michkov, Lynch , Overland, Corriden. References Ahmad R, Wojciech S, Jockers R (2014) Hunting for the function of orphan GPCRs - beyond

  11. Chemical Carcinogen (Hydrazine, Polynuclear Hydrocarbon and/or Synthetic Jet Fuel Components) Induced Carcinogenesis of Human Cells, In Vitro

    DTIC Science & Technology

    1981-08-01

    Various levels of DNA repair synthesis in Xeroderma pigmenrosum cells exposed to the carcinogens N-hydroxy and N-acetoxy-2-acetylsminofluorene...Nature (New Biol.). 238 (1972) 9. 5 V.M Maher, N. Birch, J.R. Otto and J. McCormick, Cytotoxicity of carcinogenic aro- matic amides in normal and Xeroderma ... pigmentosum fibroblasts with different DNA repair capabilities, J. Nati. Cancer Inst., 54 (1975) 1287. 6 R.H. Heflich, R.M. Hazard, L. Lommnel, J.D

  12. Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells

    DTIC Science & Technology

    2000-09-01

    Pharmacology 51: 931-940, 1996. Freemerman,AJ, Vrana J, Tombes RM, Jiang H, Chellepan SP, Fisher PB and Grant S. Effects of antisense p21 (Wafl/CIP1...gene. Mutat. Res. 403, 171-175. Vrana JA, Decker RH, Johnson CR, Wang Z, Jarvis WD, Richon VM, Ehinger M, Fisher PB and Grant S. Induction of apoptosis...centri- blue dye and trypan blue negative cells were counted fuged, washed with PBS and lysed using 100-2001il under phase contrast microscopy. of lysis

  13. Resetting the T Cell Repertoire in Prostate Cancer Bearing Host

    DTIC Science & Technology

    2009-03-01

    splenocytes were harvested and stained with fluorochrome conjugated antibodies anti CD4 (RM4.5), anti CDS (53 6.7), and anti V(3S.I+S.2 (MRS 2; BD... harvested 20 h later and analyzed by flow cytome~ for the relative abundance of CFSEiow (SV40 TAg peptide) and CFSE i (HSV peptide) populations. Detection...and spleens were harvested S days after the last injection. Cells were stained for flow cytometry analysis. This treatment did not affect either

  14. Gestational age of pregnancy loss in women with unexplained recurrent miscarriage.

    PubMed

    Ticconi, Carlo; Giuliani, Emma; Sorge, Roberto; Patrizi, Lodovico; Piccione, Emilio; Pietropolli, Adalgisa

    2016-03-01

    The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% (n = 136) experienced miscarriages within a 1-week range of GA and 53.4% (n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient. © 2015 Japan Society of Obstetrics and Gynecology.

  15. Present-day plate motions

    NASA Technical Reports Server (NTRS)

    Minster, J. B.; Jordan, T. H.

    1977-01-01

    A data set comprising 110 spreading rates, 78 transform fault azimuths and 142 earthquake slip vectors was inverted to yield a new instantaneous plate motion model, designated RM2. The mean averaging interval for the relative motion data was reduced to less than 3 My. A detailed comparison of RM2 with angular velocity vectors which best fit the data along individual plate boundaries indicates that RM2 performs close to optimally in most regions, with several notable exceptions. On the other hand, a previous estimate (RM1) failed to satisfy an extensive set of new data collected in the South Atlantic Ocean. It is shown that RM1 incorrectly predicts the plate kinematics in the South Atlantic because the presently available data are inconsistent with the plate geometry assumed in deriving RM1. It is demonstrated that this inconsistency can be remedied by postulating the existence of internal deformation with the Indian plate, although alternate explanations are possible.

  16. Experimental Study on Hot Metal Desulfurization Using Sintered Red Mud-Based Flux

    NASA Astrophysics Data System (ADS)

    Li, Fengshan; Zhang, Yanling; Guo, Zhancheng

    2017-09-01

    This research presents the results of laboratory and pilot-scale tests conducted on the use of sintered red mud (RM)-based flux in the hot metal desulfurization (HMD) process. Al2O3/Na2O in RM can decrease the melting point of lime-based slag and can work as a flux in the HMD process. Good slag fluidity was observed throughout the process, and high desulfurization rates ( 80%) with a low final S content (<0.02%) were experimentally obtained when the RM:CaO ratio was between 1.2:1 and 2.4:1. The pilot-scale test results indicated that a desulfurization rate as high as 91% and a S content <0.0099% could be acquired when RM:lime = 1:1, verifying the feasibility of using sintered RM-based flux in HMD. The data obtained provide important information for promoting the large-scale application of sintered RM in steelmaking.

  17. 78 FR 37837 - Center for Scientific Review; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ...: Basic Research on Human Embryonic Stem Cells. Date: July 16-17, 2013. Time: 8:00 a.m. to 5:00 p.m... Panel; RFA-RM-13-002: Planning Grants for the NIH National Research Mentoring Network (NRMN) P20. Date... and Related Research Integrated Review Group; NeuroAIDS and other End-Organ Diseases Study Section...

  18. Treatability Study in Support of Intrinsic Remediation for the Jet Fuel Transfer Line Southwest of Building 412 and the POL Yard. Volume 1: Text. Wisconsin Air National Guard at Truax Field, Madison, Wisconsin

    DTIC Science & Technology

    1997-01-01

    Jamison et al., 1975; Atlas , 1981, 1984, 1988; Gibson an( ’)ramanian, 1984; Reinhard et al., 1984; Young, 1984; Bartha , 1986; Wilson , 1986, 1987...Academic Press, New York, 381 p. Atlas , R.M., 1981, Microbial degradation of petroleum hydrocarbons - an environmental 0 perspective: Microbiological Reviews...biodegradation: Microbial Ecology , vol. 12, p. 155-172. Bauman, B, 1991, Biodegradation Research of the American Petroleum Institute. Presented at: In

  19. Assessment of Patient Perceptions About Web Telemonitoring Applied to Artificial Pancreas Use at Home

    PubMed Central

    Farret, Anne; Del Favero, Simone; Bruttomesso, Daniela; Renard, Eric

    2014-01-01

    Patients with chronic diseases as well as health care systems could benefit from telemedicine applications such as remote monitoring (RM). RM relies on a device that sends patients’ health data to a remote server accessible by care teams. Recent smartphone-based artificial pancreas (AP) systems collect comprehensive set of information and could therefore support the development of RM applied to diabetes. To better understand how RM could be integrated in future AP systems, we wanted to get patients’ opinion on this concept, as they are the final users of these systems. An online questionnaire with 11 items was sent to 20 experienced patients who tested AP and RM during our recent outpatient studies in France and Italy. We received 17 answers. All patients considered that during their participation in trials, RM was useful, reassuring, and essential. One-third wouldn’t have participated without it. When AP is commercialized, 88% of respondents think that AP should go with a RM tool, but it should be activated only at certain times, at first use or in case of difficulties (82%). Participants ask for technical support when a device fails (88%) and for medical help in case of prolonged hyperglycemia (65%) or severe or repeated hypoglycemia (53%), but not after each case of hypoglycemia (6%). More than 75% think that RM could help them to improve their blood glucose control. This preliminary work indicates that patients expect RM to be part of future AP development. Larger studies remain to be performed to investigate its usefulness and potential economic effectiveness. PMID:24876571

  20. Respiratory morbidity among welders in the shipbuilding industry, Goa.

    PubMed

    Bhumika, Nateshan; Prabhu, Ganapati Vasant; Ferreira, Agnelo Menino; Kulkarni, Manoj Kumar; Vaz, Frederick Satiro; Singh, Zile

    2012-05-01

    Welding is pivotal in shipbuilding. The fumes and gases involved in welding may cause respiratory morbidity. To study the prevalence of respiratory morbidity (RM) among welders vis à vis among nonwelders and its association with certain relevant factors. A cross-sectional study of 276 welders and 276 nonwelders was conducted in the shipbuilding industry. An interviewer-administered questionnaire was followed by spirometric examination. Odds ratio and its 95% CI and two-way ANOVA. Prevalence of RM was found to be significantly higher among welders compared to nonwelders (who were comparable in age, duration of employment (DOE) and smoking habits,) with odds ratio (OR) of 1.78 (95% confidence interval (CI):1.20-2.63). Obstructive type of RM was predominant in both welders (26% (n = 73)) and nonwelders (17% (n = 49)) with welders being at a significantly higher risk (OR = 1.66 (95%: 1.10-2.49)). RM was commoner after the 40 years of age or after 20 years of employment in both groups. Smoking was associated with RM among welders (OR = 1.48, 95% CI: 1.24-1.75) as well as nonwelders (OR = 2.83, 95% CI: 2.26-3.54). Work-related respiratory symptoms (WRRS) was not found to be related to RM (OR = 1.69, 95% CI: 1.00-2.84). Consistent use of personal protective equipment (PPE) was protective against RM in welders (OR = 0.33, 95% CI: 0.28-0.37). Welders had a greater burden of RM and this was related to increasing age, DOE, smoking and inconsistent use of PPE. WRRS were not indicative of RM.

  1. Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men.

    PubMed

    Shimano, Tomoko; Kraemer, William J; Spiering, Barry A; Volek, Jeff S; Hatfield, Disa L; Silvestre, Ricardo; Vingren, Jakob L; Fragala, Maren S; Maresh, Carl M; Fleck, Steven J; Newton, Robert U; Spreuwenberg, Luuk P B; Häkkinen, Keijo

    2006-11-01

    Resistance exercise intensity is commonly prescribed as a percent of 1 repetition maximum (1RM). However, the relationship between percent 1RM and the number of repetitions allowed remains poorly studied, especially using free weight exercises. The purpose of this study was to determine the maximal number of repetitions that trained (T) and untrained (UT) men can perform during free weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of 1RM in the back squat, bench press, and arm curl in a randomized, balanced design. There was a significant (p < 0.05) intensity x exercise interaction. More repetitions were performed during the back squat than the bench press or arm curl at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences between the back squat and other exercises; however, differences were much less pronounced. No differences in number of repetitions performed at a given exercise intensity were noted between T and UT (except during bench press at 90% 1RM). In conclusion, the number of repetitions performed at a given percent of 1RM is influenced by the amount of muscle mass used during the exercise, as more repetitions can be performed during the back squat than either the bench press or arm curl. Training status of the individual has a minimal impact on the number of repetitions performed at relative exercise intensity.

  2. Time until diagnosis of clinical events with different remote monitoring systems in Implantable Cardioverter-Defibrillator patients.

    PubMed

    Söth-Hansen, Malene; Witt, Christoffer Tobias; Rasmussen, Mathis; Kristensen, Jens; Gerdes, Christian; Nielsen, Jens Cosedis

    2018-05-24

    Remote monitoring (RM) is an established technology integrated into routine follow-up of patients with implantable cardioverter-defibrillator (ICD). Current RM systems differ according to transmission frequency and alert definition. We aimed to compare time difference between detection and acknowledgement of clinically relevant events between four RM systems. We analyzed time delay between detection of ventricular arrhythmic and technical events by the ICD and acknowledgement by hospital staff in 1.802 consecutive patients followed with RM during September 2014 - August 2016. Devices from Biotronik (BIO, n=374), Boston Scientific (BSC, n=196), Medtronic (MDT, n=468) and St Jude Medical (SJM, n=764) were included. We identified all events from RM webpages and their acknowledgement with RM or at in-clinic follow-up. Events occurring during weekends were excluded. We included 3.472 events. Proportion of events acknowledged within 24 hours was 72%, 23%, 18% and 65% with BIO, BSC, MDT and SJM, respectively, with median times of 13, 222, 163 and 18 hours from detection to acknowledgement (p<0.001 for both comparisons between manufacturers). Including only events transmitted as alerts by RM, 72%, 68%, 61% and 65% for BIO, BSC, MDT and SJM, respectively were acknowledged within 24 hours. Variation in time to acknowledgement of ventricular tachyarrhythmia episodes not treated with shock therapy was the primary cause for the difference between manufacturers. Significant and clinically relevant differences in time delay from event detection to acknowledgement exist between RM systems. Varying definitions of which events RM transmits as alerts are important for the differences observed. Copyright © 2018. Published by Elsevier Inc.

  3. Intestinal microbiota reduces genotoxic endpoints induced by high-energy protons.

    PubMed

    Maier, Irene; Berry, David M; Schiestl, Robert H

    2014-01-01

    Ionizing space radiation causes oxidative DNA damage and triggers oxidative stress responses, and compromised DNA repair mechanisms can lead to increased risk of carcinogenesis. Young adult mice with developed innate and adaptive immune systems that harbored either a conventional intestinal microbiota (CM) or an intestinal microbiota with a restricted microbial composition (RM) were irradiated with a total dose of 1 Gy delivered by high-energy protons (2.5 GeV/n, LET = 0.2-2 keV/μm) or silicon or iron ions (850 MeV/n, LET ≈ 50 keV/μm and 1 GeV/n, LET = 150 keV/μm, respectively). Six hours after whole-body irradiation, acute chromosomal DNA lesions were observed for RM mice but not CM mice. High-throughput rRNA gene sequencing of intestinal mucosal bacteria showed that Barnesiella intestinihominis and unclassified Bacterodiales were significantly more abundant in male RM mice than CM mice, and phylotype densities changed in irradiated mice. In addition, Helicobacter hepaticus and Bacteroides stercoris were higher in CM than RM mice. Elevated levels of persistently phosphorylated γ-H2AX were observed in RM mice exposed to high-energy protons compared to nonirradiated RM mice, and they also were associated with a decrease of the antioxidant glutathione in peripheral blood measured at four weeks after irradiation. After radiation exposure, CM mice showed lower levels of γ-H2AX phosphorylation than RM mice and an increase in specific RM-associated phylotypes, indicating a down-regulating force on DNA repair by differentially abundant phylotypes in RM versus a radiation-sensitive complex CM.

  4. The rat cochlea in the absence of circulating adrenal hormones: an electrophysiological and morphological study.

    PubMed

    Lohuis, P J; Börjesson, P K; Klis, S F; Smoorenburg, G F

    2000-05-01

    Circulating adrenal hormones affect strial function. Removal of endogenous levels of adrenal steroids by bilateral adrenalectomy (ADX) in rats causes a decrease of Na(+)/K(+)-ATPase activity in the cochlear lateral wall [Rarey et al., 1989. Arch. Otolaryngol. Head Neck Surg. 115, 817-821] and a decrease of the volume of the marginal cells in the stria vascularis [Lohuis et al., 1990. Acta Otolaryngol. (Stockh.) 110, 348-356]. To study further the effect of absence of circulating adrenocorticosteroids on cochlear function, 18 male Long Evans rats underwent either an ADX or a SHAM operation. Electrocochleography was performed 1 week after surgery for tone bursts in a frequency range of 1-16 kHz. Thereafter, the cochleas were harvested and examined histologically. No significant changes in the amplitude growth curves of the summating potential (SP), the compound action potential (CAP) and the cochlear microphonics (CM) were detected after ADX. However, visually, there appeared to be a decrease of endolymphatic volume (tentatively called imdrops). Reissner's membrane (RM) extended less into scala vestibuli in ADX animals than in SHAM-operated animals. The ratio between the length of RM and the straight distance between the medial and lateral attachment points of RM were used as an objective measure to quantify this effect in each sub-apical half turn of the cochlea. The decrease in length of RM was statistically significant. Thus, circulating adrenal hormones appear to be necessary for normal cochlear fluid homeostasis. Absence of one or more of these hormones leads to shrinkage of the scala media (imdrops). However, the absence of adrenal hormones does not affect the gross cochlear potentials. Apparently, the cochlea is capable of compensating for the absence of circulating adrenal hormones to sustain the conditions necessary for proper cochlear transduction.

  5. Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26

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

    Gudmundsson, Sanna; Wilbe, Maria; Ekvall, Sara

    Revertant mosaicism (RM) is a naturally occurring phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event. Development of healthy-looking skin due to RM has been observed in patients with various inherited skin disorders, but not in connexin-related disease. We aimed to clarify the underlying molecular mechanisms of suspected RM in the skin of a patient with keratitis-ichthyosis-deafness (KID) syndrome. The patient was diagnosed with KID syndrome due to characteristic skin lesions, hearing deficiency and keratitis. Investigation of GJB2 encoding connexin (Cx) 26 revealed heterozygosity for the recurrent de novo germline mutation, c.148G >more » A, p.Asp50Asn. At age 20, the patient developed spots of healthy-looking skin that grew in size and number within widespread erythrokeratodermic lesions. Ultra-deep sequencing of two healthy-looking skin biopsies identified five somatic nonsynonymous mutations, independently present in cis with the p.Asp50Asn mutation. Functional studies of Cx26 in HeLa cells revealed co-expression of Cx26-Asp50Asn and wild-type Cx26 in gap junction channel plaques. However, Cx26-Asp50Asn with the second-site mutations identified in the patient displayed no formation of gap junction channel plaques. We argue that the second-site mutations independently inhibit Cx26-Asp50Asn expression in gap junction channels, reverting the dominant negative effect of the p.Asp50Asn mutation. Finally to our knowledge, this is the first time RM has been reported to result in the development of healthy-looking skin in a patient with KID syndrome.« less

  6. Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26

    DOE PAGES

    Gudmundsson, Sanna; Wilbe, Maria; Ekvall, Sara; ...

    2017-02-01

    Revertant mosaicism (RM) is a naturally occurring phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event. Development of healthy-looking skin due to RM has been observed in patients with various inherited skin disorders, but not in connexin-related disease. We aimed to clarify the underlying molecular mechanisms of suspected RM in the skin of a patient with keratitis-ichthyosis-deafness (KID) syndrome. The patient was diagnosed with KID syndrome due to characteristic skin lesions, hearing deficiency and keratitis. Investigation of GJB2 encoding connexin (Cx) 26 revealed heterozygosity for the recurrent de novo germline mutation, c.148G >more » A, p.Asp50Asn. At age 20, the patient developed spots of healthy-looking skin that grew in size and number within widespread erythrokeratodermic lesions. Ultra-deep sequencing of two healthy-looking skin biopsies identified five somatic nonsynonymous mutations, independently present in cis with the p.Asp50Asn mutation. Functional studies of Cx26 in HeLa cells revealed co-expression of Cx26-Asp50Asn and wild-type Cx26 in gap junction channel plaques. However, Cx26-Asp50Asn with the second-site mutations identified in the patient displayed no formation of gap junction channel plaques. We argue that the second-site mutations independently inhibit Cx26-Asp50Asn expression in gap junction channels, reverting the dominant negative effect of the p.Asp50Asn mutation. Finally to our knowledge, this is the first time RM has been reported to result in the development of healthy-looking skin in a patient with KID syndrome.« less

  7. Kinematic dynamo action in a network of screw motions; application to the core of a fast breeder reactor

    NASA Astrophysics Data System (ADS)

    Plunian, F.; Marty, P.; Alemany, A.

    1999-03-01

    Most of the studies concerning the dynamo effect are motivated by astrophysical and geophysical applications. The dynamo effect is also the subject of some experimental studies in fast breeder reactors (FBR) for they contain liquid sodium in motion with magnetic Reynolds numbers larger than unity. In this paper, we are concerned with the flow of sodium inside the core of an FBR, characterized by a strong helicity. The sodium in the core flows through a network of vertical cylinders. In each cylinder assembly, the flow can be approximated by a smooth upwards helical motion with no-slip conditions at the boundary. As the core contains a large number of assemblies, the global flow is considered to be two-dimensionally periodic. We investigate the self-excitation of a two-dimensionally periodic magnetic field using an instability analysis of the induction equation which leads to an eigenvalue problem. Advantage is taken of the flow symmetries to reduce the size of the problem. The growth rate of the magnetic field is found as a function of the flow pitch, the magnetic Reynolds number (Rm) and the vertical magnetic wavenumber (k). An [alpha]-effect is shown to operate for moderate values of Rm, supporting a mean magnetic field. The large-Rm limit is investigated numerically. It is found that [alpha]=O(Rm[minus sign]2/3), which can be explained through appropriate dynamo mechanisms. Either a smooth Ponomarenko or a Roberts type of dynamo is operating in each periodic cell, depending on k. The standard power regime of an industrial FPBR is found to be subcritical.

  8. RM2: rms error comparisons

    NASA Technical Reports Server (NTRS)

    Rice, R. F.

    1976-01-01

    The root-mean-square error performance measure is used to compare the relative performance of several widely known source coding algorithms with the RM2 image data compression system. The results demonstrate that RM2 has a uniformly significant performance advantage.

  9. Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

    PubMed

    Marshall-Gradisnik, Sonya; Johnston, Samantha; Chacko, Anu; Nguyen, Thao; Smith, Peter; Staines, Donald

    2016-12-01

    Objective The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca 2+ ) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients. Methods A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software. Results Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3' untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group. Conclusion This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca 2+ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.

  10. Performance of health product risk management and surveillance conducted by health personnel at sub-district health promotion hospitals in the northeast region of Thailand.

    PubMed

    Kanjanarach, Tipaporn; Jaisa-Ard, Raksaworn; Poonaovarat, Nantawan

    2014-01-01

    Health personnel at sub-district health promotion hospitals (SD-HPHs) are assigned to take responsibility for 15 activities related to health product risk management and surveillance (HP-RM&S). This cross-sectional survey aimed to identify factors that determined their job performance and to record their expressed needs to support HP-RM&S operation. In this study, job performance was defined as completion of all 15 activities. Self-administered postal questionnaires were used to collect data from 380 randomly selected health personnel who were in charge of HP-RM&S at SD-HPHs in the northeast of Thailand. Thirty-six point one percent (n=137) of the respondents were able to perform all 15 of the HP-RM&S activities assigned to SD-HPHs. A logistic regression model identified three factors that statistically significantly determined the completion of all 15 HP-RM&S activities. These were: receiving a high or very high level of support from the community (adjusted odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.5, 4.1), the responsible persons for HP-RM&S did not hold an administrative position (adjusted OR: 1.7; 95% CI: 1.1, 2.7), and having at least one training session related to HP-RM&S per year (adjusted OR: 1.7; 95% CI 1.1, 2.6). There were 1,536 expressed needs which can be classified into four major categories, ie, training needs (41.6%, n=639), resource support (28.3%, n=435), mechanisms that facilitate HP-RM&S operation (24.1%, n=370) and adjusting of the scope of HP-RM&S (6.0%, n=92). The topics most frequently referred to in training needs were drug law, food law, and cosmetics law. A strategy for improvement of the job performance in HP-RM&S of health personnel in SD-HPHs should target identifying schemes to encourage the community to proactively participate in HP-RM&S. The district health office as the organization directly controlling and supervising SD-HPHs should also regularly update knowledge base and skills necessary for HP-RM&S operation through training of the responsible health personnel.

  11. Effect of Fatigue Upon Performance and Electromyographic Activity in 6-RM Bench Press

    PubMed Central

    van den Tillaar, Roland; Saeterbakken, Atle

    2014-01-01

    The aim of this study was to examine the effect of fatigue during one set of 6-RM bench pressing upon the muscle patterning and performance. Fourteen resistance-trained males (age 22.5±2.0 years, stature 1.82±0.07 m, body mass 82.0±7.8 kg) conducted a 6-RM bench press protocol. Barbell kinematics and EMG activity of pectoralis major, deltoid anterior, biceps brachii, triceps brachii, rectus abdominis, oblique external and erector spinae were measured in each repetition during the 6-RM bench press. Total lifting time increased and the velocity in the ascending movement decreased (p≤0.001). However, the kinematics in the descending phase deferred: the time decreased and velocity increased during the 6-RM (p≤0.001). Generally, muscles increased their EMG amplitude during the six repetitions in the ascending movement, while only three of the seven measured muscles showed an increase over the six repetitions in the descending part in 6-RM bench pressing. It was concluded that the bench pressing performance decreased (lower barbell velocities and longer lifting times) with increasing fatigue in the 6-RM execution. Furthermore EMG increased in the prime movers and the trunk stabilizers (abdominal and spine), while the antagonist muscle (biceps) activity was not affected by fatigue during the lifting phase in a single set of 6-RM bench pressing PMID:25031673

  12. Effect of Fatigue Upon Performance and Electromyographic Activity in 6-RM Bench Press.

    PubMed

    van den Tillaar, Roland; Saeterbakken, Atle

    2014-03-27

    The aim of this study was to examine the effect of fatigue during one set of 6-RM bench pressing upon the muscle patterning and performance. Fourteen resistance-trained males (age 22.5±2.0 years, stature 1.82±0.07 m, body mass 82.0±7.8 kg) conducted a 6-RM bench press protocol. Barbell kinematics and EMG activity of pectoralis major, deltoid anterior, biceps brachii, triceps brachii, rectus abdominis, oblique external and erector spinae were measured in each repetition during the 6-RM bench press. Total lifting time increased and the velocity in the ascending movement decreased (p≤0.001). However, the kinematics in the descending phase deferred: the time decreased and velocity increased during the 6-RM (p≤0.001). Generally, muscles increased their EMG amplitude during the six repetitions in the ascending movement, while only three of the seven measured muscles showed an increase over the six repetitions in the descending part in 6-RM bench pressing. It was concluded that the bench pressing performance decreased (lower barbell velocities and longer lifting times) with increasing fatigue in the 6-RM execution. Furthermore EMG increased in the prime movers and the trunk stabilizers (abdominal and spine), while the antagonist muscle (biceps) activity was not affected by fatigue during the lifting phase in a single set of 6-RM bench pressing.

  13. Signatures of Relativistic Helical Motion in the Rotation Measures of Active Galactic Nucleus Jets

    NASA Astrophysics Data System (ADS)

    Broderick, Avery E.; Loeb, Abraham

    2009-10-01

    Polarization has proven to be an invaluable tool for probing magnetic fields in relativistic jets. Maps of the intrinsic polarization vectors have provided the best evidence to date for uniform, toroidally dominated magnetic fields within jets. More recently, maps of the rotation measure (RM) in jets have for the first time probed the field geometry of the cool, moderately relativistic surrounding material. In most cases, clear signatures of the toroidal magnetic field are detected, corresponding to gradients in RM profiles transverse to the jet. However, in many objects, these profiles also display marked asymmetries that are difficult to explain in simple helical jet models. Furthermore, in some cases, the RM profiles are strongly frequency and/or time dependent. Here we show that these features may be naturally accounted for by including relativistic helical motion in the jet model. In particular, we are able to reproduce bent RM profiles observed in a variety of jets, frequency-dependent RM profile morphologies, and even the time dependence of the RM profiles of knots in 3C 273. Finally, we predict that some sources may show reversals in their RM profiles at sufficiently high frequencies, depending upon the ratio of the components of jet sheath velocity transverse and parallel to the jet. Thus, multi-frequency RM maps promise a novel way in which to probe the velocity structure of relativistic outflows.

  14. Establishing a proactive safety and health risk management system in the fire service.

    PubMed

    Poplin, Gerald S; Pollack, Keshia M; Griffin, Stephanie; Day-Nash, Virginia; Peate, Wayne F; Nied, Ed; Gulotta, John; Burgess, Jefferey L

    2015-04-19

    Formalized risk management (RM) is an internationally accepted process for reducing hazards in the workplace, with defined steps including hazard scoping, risk assessment, and implementation of controls, all within an iterative process. While required for all industry in the European Union and widely used elsewhere, the United States maintains a compliance-based regulatory structure, rather than one based on systematic, risk-based methodologies. Firefighting is a hazardous profession, with high injury, illness, and fatality rates compared with other occupations, and implementation of RM programs has the potential to greatly improve firefighter safety and health; however, no descriptions of RM implementation are in the peer-reviewed literature for the North American fire service. In this paper we describe the steps used to design and implement the RM process in a moderately-sized fire department, with particular focus on prioritizing and managing injury hazards during patient transport, fireground, and physical exercise procedures. Hazard scoping and formalized risk assessments are described, in addition to the identification of participatory-led injury control strategies. Process evaluation methods were conducted to primarily assess the feasibility of voluntarily instituting the RM approach within the fire service setting. The RM process was well accepted by the fire department and led to development of 45 hazard specific-interventions. Qualitative data documenting the implementation of the RM process revealed that participants emphasized the: value of the RM process, especially the participatory bottom-up approach; usefulness of the RM process for breaking down tasks to identify potential risks; and potential of RM for reducing firefighter injury. As implemented, this risk-based approach used to identify and manage occupational hazards and risks was successful and is deemed feasible for U.S. (and other) fire services. While several barriers and challenges do exist in the implementation of any intervention such as this, recommendations for adopting the process are provided. Additional work will be performed to determine the effectiveness of select controls strategies that were implemented; however participants throughout the organizational structure perceived the RM process to be of high utility while researchers also found the process improved the awareness and engagement in actively enhancing worker safety and health.

  15. The Formation of Supermassive Black Holes from Population III.1 Seeds. I. Cosmic Formation Histories and Clustering Properties

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

    Banik, Nilanjan; Tan, Jonathan C.; Monaco, Pierluigi

    We calculate the cosmic distributions in space and time of the formation sites of the first, "Pop III.1" stars, exploring a model in which these are the progenitors of all supermassive black holes (SMBHs). Pop III.1 stars are defined to form from primordial composition gas in dark matter minihalos withmore » $$\\sim10^6\\:M_\\odot$$ that are isolated from neighboring astrophysical sources by a given isolation distance, $$d_{\\rm{iso}}$$. We assume Pop III.1 sources are seeds of SMBHs, based on protostellar support by dark matter annihilation heating that allows them to accrete a large fraction of their minihalo gas, i.e., $$\\sim 10^5\\:M_\\odot$$. Exploring $$d_{\\rm{iso}}$$ from 10--$$100\\:\\rm{kpc}$$ (proper distances), we predict the redshift evolution of Pop III.1 source and SMBH remnant number densities. The local, $z=0$ density of SMBHs constrains $$d_{\\rm{iso}}\\lesssim 100\\:\\rm{kpc}$$ (i.e., $$3\\:\\rm{Mpc}$$ comoving distance at $$z\\simeq30$$). In our simulated ($$\\sim60\\:\\rm{Mpc}$$)$^3$ comoving volume, Pop III.1 stars start forming just after $z=40$. Their formation is largely complete by $$z\\simeq25$$ to 20 for $$d_{\\rm{iso}}=100$$ to $$50\\:\\rm{kpc}$$. We follow source evolution to $z=10$, by which point most SMBHs reside in halos with $$\\gtrsim10^8\\:M_\\odot$$. Over this period, there is relatively limited merging of SMBHs for these values of $$d_{\\rm{iso}}$$. We also predict SMBH clustering properties at $z=10$$: feedback suppression of neighboring sources leads to relatively flat angular correlation functions. Finally, we consider a simple "Str\\"omgren" model for $$d_{\\rm iso}$, based on ionizing feedback from zero age main sequence supermassive Pop III.1 stars that may be the direct progenitors of SMBHs in this scenario. Such models naturally produce feedback effects on scales of $$\\sim100\\:$$kpc and thus self-consistently generate a SMBH number density similar to the observed value.« less

  16. Validity of a Commercial Linear Encoder to Estimate Bench Press 1 RM from the Force-Velocity Relationship.

    PubMed

    Bosquet, Laurent; Porta-Benache, Jeremy; Blais, Jérôme

    2010-01-01

    The aim of this study was to assess the validity and accuracy of a commercial linear encoder (Musclelab, Ergotest, Norway) to estimate Bench press 1 repetition maximum (1RM) from the force - velocity relationship. Twenty seven physical education students and teachers (5 women and 22 men) with a heterogeneous history of strength training participated in this study. They performed a 1 RM test and a force - velocity test using a Bench press lifting task in a random order. Mean 1 RM was 61.8 ± 15.3 kg (range: 34 to 100 kg), while 1 RM estimated by the Musclelab's software from the force-velocity relationship was 56.4 ± 14.0 kg (range: 33 to 91 kg). Actual and estimated 1 RM were very highly correlated (r = 0.93, p<0.001) but largely different (Bias: 5.4 ± 5.7 kg, p < 0.001, ES = 1.37). The 95% limits of agreement were ±11.2 kg, which represented ±18% of actual 1 RM. It was concluded that 1 RM estimated from the force-velocity relationship was a good measure for monitoring training induced adaptations, but also that it was not accurate enough to prescribe training intensities. Additional studies are required to determine whether accuracy is affected by age, sex or initial level. Key pointsSome commercial devices allow to estimate 1 RM from the force-velocity relationship.These estimations are valid. However, their accuracy is not high enough to be of practical help for training intensity prescription.Day-to-day reliability of force and velocity measured by the linear encoder has been shown to be very high, but the specific reliability of 1 RM estimated from the force-velocity relationship has to be determined before concluding to the usefulness of this approach in the monitoring of training induced adaptations.

  17. Validity of a Commercial Linear Encoder to Estimate Bench Press 1 RM from the Force-Velocity Relationship

    PubMed Central

    Bosquet, Laurent; Porta-Benache, Jeremy; Blais, Jérôme

    2010-01-01

    The aim of this study was to assess the validity and accuracy of a commercial linear encoder (Musclelab, Ergotest, Norway) to estimate Bench press 1 repetition maximum (1RM) from the force - velocity relationship. Twenty seven physical education students and teachers (5 women and 22 men) with a heterogeneous history of strength training participated in this study. They performed a 1 RM test and a force - velocity test using a Bench press lifting task in a random order. Mean 1 RM was 61.8 ± 15.3 kg (range: 34 to 100 kg), while 1 RM estimated by the Musclelab’s software from the force-velocity relationship was 56.4 ± 14.0 kg (range: 33 to 91 kg). Actual and estimated 1 RM were very highly correlated (r = 0.93, p<0.001) but largely different (Bias: 5.4 ± 5.7 kg, p < 0.001, ES = 1.37). The 95% limits of agreement were ±11.2 kg, which represented ±18% of actual 1 RM. It was concluded that 1 RM estimated from the force-velocity relationship was a good measure for monitoring training induced adaptations, but also that it was not accurate enough to prescribe training intensities. Additional studies are required to determine whether accuracy is affected by age, sex or initial level. Key points Some commercial devices allow to estimate 1 RM from the force-velocity relationship. These estimations are valid. However, their accuracy is not high enough to be of practical help for training intensity prescription. Day-to-day reliability of force and velocity measured by the linear encoder has been shown to be very high, but the specific reliability of 1 RM estimated from the force-velocity relationship has to be determined before concluding to the usefulness of this approach in the monitoring of training induced adaptations. PMID:24149641

  18. Effect of a mixture of iprobenfos and malathion on the development of malathion resistance in the mosquito Culex pipiens pallens Coq.

    PubMed

    Tao, Li-Ming; Yang, Jian-Zhong; Zhuang, Pei-Jun; Tang, Zhen-Hua

    2006-01-01

    A malathion-resistant (RM) strain of Culex pipiens pallens Coq was obtained by successively selecting a field population with malathion in the laboratory. The synergistic effect of iprobenfos on malathion toxicity and alpha-naphthyl acetate (alpha-NA) esterase assay revealed that malathion resistance in the RM strain was associated with increased alpha-NA esterase activity and the synergism was mainly due to the inhibition by iprobenfos of this activity. There was no difference in alpha-NA esterase activity between the larvae and female adults in the susceptible (S) strain, but the activity in the adults was 13-fold higher than in the larvae of the RM strain. To understand the effect of the application of a mixture of iprobenfos and malathion on the evolution of malathion resistance, an artificial strain (Syn) was generated by mixing the RM and S strains with 0.1 frequency of the malathion-resistant individuals. The offspring of the Syn strain were divided into two sub-strains, Rm and Rm+ibp, which were successively treated with, respectively, malathion alone and malathion + iprobenfos (1:2) at LC70. In the mixture, the fungicide iprobenfos acted as a synergist of malathion. After treatment for 10 generations, the resistance level to malathion was 317.4-fold for the Rm sub-strain, whereas for the Rm+ibp sub-strain it was only 38.9-fold, compared with the Syn strain. Similar results were obtained by measurement of alpha-NA esterase activity from both larvae and female adults. The alpha-NA esterase activities in larvae and female adults at F10 generation were 2.6- and 10.9-fold from the Rm+ibp sub-strain and 5.7- and 98.5-fold from the Rm sub-strain, respectively, compared with the Syn strain. The above results suggested that iprobenfos, although it cannot completely stop or prevent the onset of malathion resistance, could dramatically delay its evolution. Copyright 2005 Society of Chemical Industry.

  19. Improvement of FK506 Production in the High-Yielding Strain Streptomyces sp. RM7011 by Engineering the Supply of Allylmalonyl-CoA Through a Combination of Genetic and Chemical Approach.

    PubMed

    Mo, SangJoon; Lee, Sung-Kwon; Jin, Ying-Yu; Suh, Joo-Won

    2016-02-01

    FK506, a widely used immunosuppressant, is a 23-membered polyketide macrolide that is produced by several Streptomyces species. FK506 high-yielding strain Streptomyces sp. RM7011 was developed from the discovered Streptomyces sp. KCCM 11116P by random mutagenesis in our previous study. The results of transcript expression analysis showed that the transcription levels of tcsA, B, C, and D were increased in Streptomyces sp. RM7011 by 2.1-, 3.1-, 3.3-, and 4.1- fold, respectively, compared with Streptomyces sp. KCCM 11116P. The overexpression of tcsABCD genes in Streptomyces sp. RM7011 gave rise to approximately 2.5-fold (238.1 μg/ml) increase in the level of FK506 production compared with that of Streptomyces sp. RM7011. When vinyl pentanoate was added into the culture broth of Streptomyces sp. RM7011, the level of FK506 production was approximately 2.2-fold (207.7 μg/ml) higher than that of the unsupplemented fermentation. Furthermore, supplementing the culture broth of Streptomyces sp. RM7011 expressing tcsABCD genes with vinyl pentanoate resulted in an additional 1.7-fold improvement in the FK506 titer (498.1 μg/ml) compared with that observed under nonsupplemented condition. Overall, the level of FK506 production was increased approximately 5.2-fold by engineering the supply of allylmalonyl-CoA in the high-yielding strain Streptomyces sp. RM7011, using a combination of overexpressing tcsABCD genes and adding vinyl pentanoate, as compared with Streptomyces sp. RM7011 (95.3 μg/ml). Moreover, among the three precursors analyzed, pentanoate was the most effective precursor, supporting the highest titer of FK506 in the FK506 high-yielding strain Streptomyces sp. RM7011.

  20. Restoration of red mud deposits by naturally growing vegetation.

    PubMed

    Mishra, Tripti; Singh, N B; Singh, Nandita

    2017-05-04

    Disposal of red mud (RM) poses serious environmental problems such as wind erosion, air and water pollution. To overcome these problems, effective restoration of the disposal land through naturally growing vegetation is a sustainable and economical approach. The present study involved estimation of frequency (F), density (D), abundance (Ab), and important value index (IVI) of natural flora on abandoned RM sites in order to assess their metal toxicity tolerance capacity. Based on visual observations and highest IVI, S. Asper and S. punicea were identified as effective ecological tools for the restoration of barren RM sites. From the study, remarkable differences were observed between non-rhizospheric and rhizospheric RM of both species. These rhizospheric RM analyses confirm the ability of S. asper and S. punicea for enhancing the biological activities of abandoned RM. Translocation factor (TF) of iron was maximum (2.58) in S. asper, and bioconcentration factor (BCF) was found maximum (1.25) in S. punicea, but both TF (2.58) and BCF (1.35) were high in S. asper. Therefore, this plant could be reported as an iron hyperaccumulator plant. These results suggest that these plant species can be exploited for effective restoration of RM deposited land without any inputs or maintenance.

  1. Graphic methods for interpreting longitudinal dyadic patterns from repeated-measures actor-partner interdependence models.

    PubMed

    Perry, Nicholas S; Baucom, Katherine J W; Bourne, Stacia; Butner, Jonathan; Crenshaw, Alexander O; Hogan, Jasara N; Imel, Zac E; Wiltshire, Travis J; Baucom, Brian R W

    2017-08-01

    Researchers commonly use repeated-measures actor-partner interdependence models (RM-APIM) to understand how romantic partners change in relation to one another over time. However, traditional interpretations of the results of these models do not fully or correctly capture the dyadic temporal patterns estimated in RM-APIM. Interpretation of results from these models largely focuses on the meaning of single-parameter estimates in isolation from all the others. However, considering individual coefficients separately impedes the understanding of how these associations combine to produce an interdependent pattern that emerges over time. Additionally, positive within-person, or actor, effects are commonly misinterpreted as indicating growth from one time point to the next when they actually represent decline. We suggest that change-as-outcome RM-APIMs and vector field diagrams (VFDs) can be used to improve the understanding and presentation of dyadic patterns of association described by standard RM-APIMs. The current article briefly reviews the conceptual foundations of RM-APIMs, demonstrates how change-as-outcome RM-APIMs and VFDs can aid interpretation of standard RM-APIMs, and provides a tutorial in making VFDs using multilevel modeling. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Yersinia ruckeri sp. nov., the redmouth (RM) bacterium

    USGS Publications Warehouse

    Ewing, W.H.; Ross, A.J.; Brenner, Don J.; Fanning, G. R.

    1978-01-01

    Cultures of the redmouth (RM) bacterium, one of the etiological agents of redmouth disease in rainbow trout (Salmo gairdneri) and certain other fishes, were characterized by means of their biochemical reactions, by deoxyribonucleic acid (DNA) hybridization, and by determination of guanine-plus-cytosine (G+C) ratios in DNA. The DNA relatedness studies confirmed the fact that the RM bacteria are members of the family Enterobacteriaceae and that they comprise a single species that is not closely related to any other species of Enterobacteriaceae. They are about 30% related to species of both Serratia and Yersinia. A comparison of the biochemical reactions of RM bacteria and serratiae indicated that there are many differences between these organisms and that biochemically the RM bacteria are most closely related to yersiniae. The G+C ratios of RM bacteria were approximated to be between 47.5 and 48.5% These values are similar to those of yersiniae but markedly different from those of serratiae. On the basis of their biochemical reactions and their G+C ratios, the RM bacteria are considered to be a new species of Yersinia, for which the name Yersinia ruckeri is proposed. Strain 2396-61 (= ATCC 29473) is designated the type strain of the species.

  3. Reliability of Strength Testing using the Advanced Resistive Exercise Device and Free Weights

    NASA Technical Reports Server (NTRS)

    English, Kirk L.; Loehr, James A.; Laughlin, Mitzi A.; Lee, Stuart M. C.; Hagan, R. Donald

    2008-01-01

    The Advanced Resistive Exercise Device (ARED) was developed for use on the International Space Station as a countermeasure against muscle atrophy and decreased strength. This investigation examined the reliability of one-repetition maximum (1RM) strength testing using ARED and traditional free weight (FW) exercise. Methods: Six males (180.8 +/- 4.3 cm, 83.6 +/- 6.4 kg, 36 +/- 8 y, mean +/- SD) who had not engaged in resistive exercise for at least six months volunteered to participate in this project. Subjects completed four 1RM testing sessions each for FW and ARED (eight total sessions) using a balanced, randomized, crossover design. All testing using one device was completed before progressing to the other. During each session, 1RM was measured for the squat, heel raise, and deadlift exercises. Generalizability (G) and intraclass correlation coefficients (ICC) were calculated for each exercise on each device and were used to predict the number of sessions needed to obtain a reliable 1RM measurement (G . 0.90). Interclass reliability coefficients and Pearson's correlation coefficients (R) also were calculated for the highest 1RM value (1RM9sub peak)) obtained for each exercise on each device to quantify 1RM relationships between devices.

  4. Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

    PubMed

    Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

    2015-04-01

    Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P < 0.05). Cadmium chloride appeared to counteract the slow development caused by the TF constructs in two TF treatments (P < 0.05). The 4 ppt sodium chloride treatment for the RM system decreased % hatch (P < 0.05) and slowed development. In the case of nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

  5. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    PubMed

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P<0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. LANDSAT-D data format control book. Volume 6, appendix K: Unprocessed multispectral scanner high density tape (HDT-RM/HDT-GM)

    NASA Technical Reports Server (NTRS)

    Andersen, K. E.

    1981-01-01

    Unprocessed MSS data which is recorded on HDT-RM (a 28 track, high density tape) and on HDT-GM (a 14 track, nonbias recorded, high density tape) are inputs for the LANDSAT 4 data management system. All MSS data initially recorded on HDT-GM are copied to HDT-RM prior to processing. This specification establishes the requirements for the format of the LANDSAT D HDT-RM/HDT-GM.

  7. Crystal structure and characterization of a novel L-serine ammonia-lyase from Rhizomucor miehei

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

    Qin, Zhen; Yan, Qiaojuan; Ma, Qingjun

    L-serine ammonia-lyase, as a member of the β-family of pyridoxal-5′-phosphate (PLP) dependent enzymes, catalyzes the conversion of L-serine (L-threonine) to pyruvate (α-ketobutyrate) and ammonia. The crystal structure of L-serine ammonia-lyase from Rhizomucor miehei (RmSDH) was solved at 1.76 Å resolution by X-ray diffraction method. The overall structure of RmSDH had the characteristic β-family PLP dependent enzyme fold. It consisted of two distinct domains, both of which show the typical open twisted α/β structure. A PLP cofactor was located in the crevice between the two domains, which was attached to Lys52 by a Schiff-base linkage. Unique residue substitutions (Gly78, Pro79, Ser146, Ser147more » and Thr312) were discovered at the catalytic site of RmSDH by comparison of structures of RmSDH and other reported eukaryotic L-serine ammonia-lyases. Optimal pH and temperature of the purified RmSDH were 7.5 and 40 °C, respectively. It was stable in the pH range of 7.0–9.0 and at temperatures below 40 °C. This is the first crystal structure of a fungal L-serine ammonia-lyase. It will be useful to study the catalytic mechanism of β-elimination enzymes and will provide a basis for further enzyme engineering. - Highlights: • The crystal structure of a fungal L-serine ammonia-lyase (RmSDH) was solved. • Five unique residue substitutions are found at the catalytic site of RmSDH. • RmSDH was expressed in Pichia. pastoris and biochemically characterized. • RmSDH has potential application in splitting D/L-serine.« less

  8. Reticulate melanism in western painted turtles (Chrysemys picta bellii): Exploring linkages with habitat and heating rates

    USGS Publications Warehouse

    Gronke, W.K.; Chipps, S.R.; Bandas, S.J.; Higgins, K.F.

    2006-01-01

    In western painted turtles (Chrysemys picta bellii), males often exhibit one of two morphs: (1) a reticulated form, characterized by an intricate network of dark markings on the carapace or (2) a non-reticulated form. Although several hypotheses have been proposed to explain the adaptive significance of reticulate melanism (RM) on western painted turtles, no attempts have been made to document whether RM is linked to habitat conditions or if the presence of melanism affects heating rates. To evaluate these questions, we compared the frequency of adult male turtles with RM across three different habitats: riverine (rivers), lacustrine (lakes) and palustrine (wetland) habitats. Using manipulative experiments, we also tested the hypothesis that body heating rates are higher in turtles with RM. Reticulate melanism occurred on 99 (31%) of 320 male turtles captured in South Dakota from 2002 to 2003. Turtles with reticulate melanism were significantly larger than non-reticulated turtles; RM was not observed on male turtles with carapace lengths 15 cm carapace length) with RM was similar among river (0.54), lake (0.50) and wetland (0.64) habitats, implying that RM is not a habitat-linked trait. Heating rates for turtles with RM were similar to those measured for non-reticulated individuals. Body size, however, influenced heating rates; larger-bodied turtles with lower surface area-to-volume ratio heated more slowly than smaller turtles. Whether RM is a by-product of hormonal regulation or serves an adaptive purpose remains unclear. However, other hypotheses, especially those involving communication (e.g., courtship behavior) and/or gamete protection remain untested for western painted turtles and warrant further investigation.

  9. Relationships between Mechanical Variables in the Traditional and Close-Grip Bench Press.

    PubMed

    Lockie, Robert G; Callaghan, Samuel J; Moreno, Matthew R; Risso, Fabrice G; Liu, Tricia M; Stage, Alyssa A; Birmingham-Babauta, Samantha A; Stokes, John J; Giuliano, Dominic V; Lazar, Adrina; Davis, DeShaun L; Orjalo, Ashley J

    2017-12-01

    The study aim was to determine relationships between mechanical variables in the one-repetition maximum (1RM) traditional bench press (TBP) and close-grip bench press (CGBP). Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP was performed with the preferred grip; the CGBP with a grip width of 95% biacromial distance. A linear position transducer measured: lift distance and duration; work; and peak and mean power, velocity, and force. Paired samples t-tests (p < 0.05) compared the 1RM and mechanical variables for the TBP and CGBP; effect sizes (d) were also calculated. Pearson's correlations (r; p < 0.05) computed relationships between the TBP and CGBP. 1RM, lift duration, and mean force were greater in the TBP (d = 0.30-3.20). Peak power and velocity was greater for the CGBP (d = 0.50-1.29). The 1RM TBP correlated with CGBP 1RM, power, and force (r = 0.685-0.982). TBP work correlated with CGBP 1RM, lift distance, power, force, and work (r = 0.542-0.931). TBP power correlated with CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704). TBP peak and mean force related to CGBP 1RM, power, and force (r = 0.596-0.980). Due to relationships between the load, work, power, and force for the TBP and CGBP, the CGBP could provide similar strength adaptations to the TBP with long-term use. The velocity profile for the CGBP was different to that of the TBP. The CGBP could be used specifically to improve high-velocity, upper-body pushing movements.

  10. Effect of processed and red meat on endogenous nitrosation and DNA damage.

    PubMed

    Joosen, Annemiek M C P; Kuhnle, Gunter G C; Aspinall, Sue M; Barrow, Timothy M; Lecommandeur, Emmanuelle; Azqueta, Amaya; Collins, Andrew R; Bingham, Sheila A

    2009-08-01

    Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and associated supernatants for genotoxicity. Means are adjusted for differences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 +/- 19 nmol/g versus RM 185 +/- 22 nmol/g; P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% versus PM 54%; P < 0.0001) and less nitrosothiols (RM 12% versus PM 19%; P < 0.01) and other NOC (RM 10% versus PM 27%; P < 0.0001). There was no statistically significant difference in DNA breaks induced by faecal water (FW) following PM and RM diets (P = 0.80). However, PM resulted in higher levels of oxidized pyrimidines (P < 0.05). Surprisingly, VEG diets resulted in significantly more FW-induced DNA strand breaks than the meat diets (P < 0.05), which needs to be clarified in further studies. Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage.

  11. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

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

    Leone, Angelique; Nie, Alex; Brandon Parker, J.

    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit tomore » the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.« less

  12. The development of a repetition-load scheme for the eccentric-only bench press exercise.

    PubMed

    Moir, Gavin L; Erny, Kyle F; Davis, Shala E; Guers, John J; Witmer, Chad A

    2013-01-01

    The purpose of the present study was to develop a repetition-load scheme for the eccentric-only bench press exercise. Nine resistance trained men (age: 21.6 ± 1.0 years; 1-repetition maximum [RM] bench press: 137.7 ± 30.4 kg) attended four testing sessions during a four week period. During the first session each subject's 1-RM bench press load utilizing the stretch-shortening cycle was determined. During the remaining sessions they performed eccentric-only repetitions to failure using supra-maximal loads equivalent to 110%, 120% and 130% of their 1-RM value with a constant cadence (30 reps·min(-1)). Force plates and a three dimensional motion analysis system were used during these final three sessions in order to evaluate kinematic and kinetic variables. More repetitions were completed during the 110% 1-RM condition compared to the 130% 1-RM condition (p=0.01). Mean total work (p=0.046) as well as vertical force (p=0.049), vertical work (p=0.017), and vertical power output (p=0.05) were significantly greater during the 130% 1-RM condition compared to the 110% 1-RM condition. A linear function was fitted to the number of repetitions completed under each load condition that allowed the determination of the maximum number of repetitions that could be completed under other supra-maximal loads. This linear function predicted an eccentric-only 1-RM in the bench press with a load equivalent to 164.8% 1-RM, producing a load of 227.0 ± 50.0 kg. The repetition-load scheme presented here should provide a starting point for researchers to investigate the kinematic, kinetic and metabolic responses to eccentric-only bench press workouts.

  13. Respiratory morbidity among welders in the shipbuilding industry, Goa

    PubMed Central

    Bhumika, Nateshan; Prabhu, Ganapati Vasant; Ferreira, Agnelo Menino; Kulkarni, Manoj Kumar; Vaz, Frederick Satiro; Singh, Zile

    2012-01-01

    Context: Welding is pivotal in shipbuilding. The fumes and gases involved in welding may cause respiratory morbidity. Aim: To study the prevalence of respiratory morbidity (RM) among welders vis à vis among nonwelders and its association with certain relevant factors. Settings and Design: A cross-sectional study of 276 welders and 276 nonwelders was conducted in the shipbuilding industry. Materials and Methods: An interviewer-administered questionnaire was followed by spirometric examination. Statistical Analysis: Odds ratio and its 95% CI and two-way ANOVA. Results: Prevalence of RM was found to be significantly higher among welders compared to nonwelders (who were comparable in age, duration of employment (DOE) and smoking habits,) with odds ratio (OR) of 1.78 (95% confidence interval (CI):1.20-2.63). Obstructive type of RM was predominant in both welders (26% (n = 73)) and nonwelders (17% (n = 49)) with welders being at a significantly higher risk (OR = 1.66 (95%: 1.10-2.49)). RM was commoner after the 40 years of age or after 20 years of employment in both groups. Smoking was associated with RM among welders (OR = 1.48, 95% CI: 1.24-1.75) as well as nonwelders (OR = 2.83, 95% CI: 2.26-3.54). Work-related respiratory symptoms (WRRS) was not found to be related to RM (OR = 1.69, 95% CI: 1.00-2.84). Consistent use of personal protective equipment (PPE) was protective against RM in welders (OR = 0.33, 95% CI: 0.28-0.37). Conclusion: Welders had a greater burden of RM and this was related to increasing age, DOE, smoking and inconsistent use of PPE. WRRS were not indicative of RM. PMID:23580835

  14. Relationships between Mechanical Variables in the Traditional and Close-Grip Bench Press

    PubMed Central

    Callaghan, Samuel J.; Moreno, Matthew R.; Risso, Fabrice G.; Liu, Tricia M.; Stage, Alyssa A.; Birmingham-Babauta, Samantha A.; Stokes, John J.; Giuliano, Dominic V.; Lazar, Adrina; Davis, DeShaun L.; Orjalo, Ashley J.

    2017-01-01

    Abstract The study aim was to determine relationships between mechanical variables in the one-repetition maximum (1RM) traditional bench press (TBP) and close-grip bench press (CGBP). Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP was performed with the preferred grip; the CGBP with a grip width of 95% biacromial distance. A linear position transducer measured: lift distance and duration; work; and peak and mean power, velocity, and force. Paired samples t-tests (p < 0.05) compared the 1RM and mechanical variables for the TBP and CGBP; effect sizes (d) were also calculated. Pearson’s correlations (r; p < 0.05) computed relationships between the TBP and CGBP. 1RM, lift duration, and mean force were greater in the TBP (d = 0.30-3.20). Peak power and velocity was greater for the CGBP (d = 0.50-1.29). The 1RM TBP correlated with CGBP 1RM, power, and force (r = 0.685-0.982). TBP work correlated with CGBP 1RM, lift distance, power, force, and work (r = 0.542-0.931). TBP power correlated with CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704). TBP peak and mean force related to CGBP 1RM, power, and force (r = 0.596-0.980). Due to relationships between the load, work, power, and force for the TBP and CGBP, the CGBP could provide similar strength adaptations to the TBP with long-term use. The velocity profile for the CGBP was different to that of the TBP. The CGBP could be used specifically to improve high-velocity, upper-body pushing movements. PMID:29339982

  15. The Development of a Repetition-Load Scheme for the Eccentric-Only Bench Press Exercise

    PubMed Central

    Moir, Gavin L.; Erny, Kyle F.; Davis, Shala E.; Guers, John J.; Witmer, Chad A.

    2013-01-01

    The purpose of the present study was to develop a repetition-load scheme for the eccentric-only bench press exercise. Nine resistance trained men (age: 21.6 ± 1.0 years; 1-repetition maximum [RM] bench press: 137.7 ± 30.4 kg) attended four testing sessions during a four week period. During the first session each subject’s 1-RM bench press load utilizing the stretch-shortening cycle was determined. During the remaining sessions they performed eccentric-only repetitions to failure using supra-maximal loads equivalent to 110%, 120% and 130% of their 1-RM value with a constant cadence (30 reps·min−1). Force plates and a three dimensional motion analysis system were used during these final three sessions in order to evaluate kinematic and kinetic variables. More repetitions were completed during the 110% 1-RM condition compared to the 130% 1-RM condition (p=0.01). Mean total work (p=0.046) as well as vertical force (p=0.049), vertical work (p=0.017), and vertical power output (p=0.05) were significantly greater during the 130% 1-RM condition compared to the 110% 1-RM condition. A linear function was fitted to the number of repetitions completed under each load condition that allowed the determination of the maximum number of repetitions that could be completed under other supra-maximal loads. This linear function predicted an eccentric-only 1-RM in the bench press with a load equivalent to 164.8% 1-RM, producing a load of 227.0 ± 50.0 kg. The repetition-load scheme presented here should provide a starting point for researchers to investigate the kinematic, kinetic and metabolic responses to eccentric-only bench press workouts. PMID:24235981

  16. In vitro characterization of the effects of rat/mouse hemokinin-1 on mouse colonic contractile activity: a comparison with substance P.

    PubMed

    Kong, Zi-Qing; Han, Min; Yang, Wen-Le; Zhao, You-Li; Fu, Cai-Yun; Tao, Yan; Chen, Qiang; Wang, Rui

    2009-06-01

    Rat/mouse hemokinin-1 (r/m HK-1) has been identified as a member of the tachykinin family and its effect in colonic contractile activity remains unknown. We investigated the effects and mechanisms of actions of r/m HK-1 on the mouse colonic contractile activity in vitro by comparing it with that of substance P (SP). R/m HK-1 induced substantial contractions on the circular muscle of mouse colon. The maximal contractile responses to r/m HK-1 varied significantly among proximal-, mid- and distal-colon, suggesting that the action of r/m HK-1 was region-specific in mouse colon. The contractile response induced by r/m HK-1 is primarily via activation of tachykinin NK(1) receptors leading to activation of cholinergic excitatory pathways and with a minor contribution of NK(2) receptors, which may be on the smooth muscle itself. A direct action on colonic smooth muscles may be also involved. In contrast, SP induced biphasic colonic responses (contractile and relaxant responses) on the circular muscle, in which the contractile action of SP was equieffective with r/m HK-1. SP exerted its contractile effect predominantly through neural and muscular tachykinin NK(1) receptors, but unlike r/m HK-1 did not appear to act via NK(2) receptors. The relaxation induced by SP was largely due to release of nitric oxide (NO) produced via an action on neural NK(1) receptors. These results indicate that the receptors and the activation properties involved in r/m HK-1-induced mouse colonic contractile activity are different from those of SP.

  17. Parental Restriction of Mature-rated Media and Its Association with Substance Use among Argentinian Adolescents

    PubMed Central

    Mejia, Raul; Pérez, Adriana; Peña, Lorena; Morello, Paola; Kollath-Cattano, Christy; Braun, Sandra; Thrashe, James F.; Sargent, James D.

    2016-01-01

    Objective To assess the independent relation between parental restrictions on mature-rated media (M-RM) and substance use among South American adolescents. Methods Cross-sectional school-based youth survey of n=3,172 students (mean age 12.8 years; 57.6% boys) in three large Argentinian cities. The anonymous survey queried tobacco, alcohol, and drug use using items adapted from global youth surveys. Adolescents reported M-RM restriction for internet and videogames use, television programming and movies rated for adults. Multivariate logistic regression models assessed the association between parental M-RM restriction and substance use after adjusting for hourly media use, measures of authoritative parenting style, sociodemographics, and sensation seeking. Results Substance use rates were 10% for current smoking, 32% for current drinking alcohol, 17% for past 30-day binge drinking, and 8% for illicit drug use (marijuana or cocaine). Half of respondents reported parental M-RM restriction (internet 52%, TV 43%, adult movies 34%, videogame 25%). Parental M-RM restriction was only modestly correlated with authoritative parenting measures. In multivariate analyses M-RM restriction on all four venues was strongly protective for all substance use outcomes. Compared with no restriction, odds ratios for substance use for full restrictions were 0.32 (0.18–0.59), 0.53 (0.38–0.07), 0.36 (0.22–0.59), and 0.49 (0.26–0.92) for current smoking, drinking, binge drinking, and illicit drug use respectively. The most important single M-RM venue was movies. Conclusion This study confirms the protective association between parental M-RM restriction during adolescence and multiple substance use outcomes, including illicit drugs. M-RM restriction is independent of traditional parenting measures. The preponderance of the evidence supports intervention development. PMID:26615087

  18. Evolution of shuttle avionics redundancy management/fault tolerance

    NASA Technical Reports Server (NTRS)

    Boykin, J. C.; Thibodeau, J. R.; Schneider, H. E.

    1985-01-01

    The challenge of providing redundancy management (RM) and fault tolerance to meet the Shuttle Program requirements of fail operational/fail safe for the avionics systems was complicated by the critical program constraints of weight, cost, and schedule. The basic and sometimes false effectivity of less than pure RM designs is addressed. Evolution of the multiple input selection filter (the heart of the RM function) is discussed with emphasis on the subtle interactions of the flight control system that were found to be potentially catastrophic. Several other general RM development problems are discussed, with particular emphasis on the inertial measurement unit RM, indicative of the complexity of managing that three string system and its critical interfaces with the guidance and control systems.

  19. Using the load-velocity relationship for 1RM prediction.

    PubMed

    Jidovtseff, Boris; Harris, Nigel K; Crielaard, Jean-Michel; Cronin, John B

    2011-01-01

    The purpose of this study was to investigate the ability of the load-velocity relationship to accurately predict a bench press 1 repetition maximum (1RM). Data from 3 different bench press studies (n = 112) that incorporated both 1RM assessment and submaximal load-velocity profiling were analyzed. Individual regression analysis was performed to determine the theoretical load at zero velocity (LD0). Data from each of the 3 studies were analyzed separately and also presented as overall group mean. Thereafter, correlation analysis provided quantification of the relationships between 1RM and LD0. Practically perfect correlations (r = ∼0.95) were observed in our samples, confirming the ability of the load-velocity profile to accurately predict bench press 1RM.

  20. Restoration of Tumor Immune Surveillance via Targeting of IL-13Receptor-α2

    PubMed Central

    Fichtner-Feigl, Stefan; Terabe, Masaki; Kitani, Atsushi; Young, Cheryl A.; Fuss, Ivan; Geissler, Edward K.; Schlitt, Hans-Jürgen; Berzofsky, Jay A.; Strober, Warren

    2009-01-01

    In previous studies we described a “counter-immunosurveillance” mechanism initiated by tumor-activated, IL-13-producing NKT cells that signal Gr-1+ cells to produce TGF-β1, a cytokine that suppresses the activity of tumor-inhibiting cytolytic CD8+ T cells. Here we show that in two tumor models (the CT-26 metastatic colon cancer and the 15-12RM fibrosarcoma regressor models) this counter-surveillance mechanism requires the expression of a novel IL-13 receptor, IL-13Rα2, on Gr-1intermediate cells, since down-regulation of IL-13Rα2 expression or the AP-1 signal generated by the receptor via in vivo administration of specific siRNA or decoy oligonucleotides leads to loss of TGF-β1 production. Furthermore, acting on prior studies showing that IL-13Rα2 expression is induced (in part) by TNF-α, we show that receptor expression and TGF-β1 production is inhibited by administration of a TNF-α neutralizing substance, TNF-αR-Fc (etanercept). Taking advantage of this latter fact, we then demonstrate in the CT-26 model that counter-immunosurveillance could be inhibited, anti-CT-26-specific CD8+ cytolytic activity restored, and CT-26 metastatic tumor nodules greatly decreased by administration of TNF-αR-Fc. Corroborative data was obtained using the 15-12RM fibrosarcoma model. These studies point to the prevention of metastatic cancer with an available agent with already known clinically acceptable adverse effects and toxicity. PMID:18451175

  1. A 2500 deg 2 CMB Lensing Map from Combined South Pole Telescope and Planck Data

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

    Omori, Y.; Chown, R.; Simard, G.

    We present a cosmic microwave background (CMB) lensing map produced from a linear combination of South Pole Telescope (SPT) and \\emph{Planck} temperature data. The 150 GHz temperature data from themore » $$2500\\ {\\rm deg}^{2}$$ SPT-SZ survey is combined with the \\emph{Planck} 143 GHz data in harmonic space, to obtain a temperature map that has a broader $$\\ell$$ coverage and less noise than either individual map. Using a quadratic estimator technique on this combined temperature map, we produce a map of the gravitational lensing potential projected along the line of sight. We measure the auto-spectrum of the lensing potential $$C_{L}^{\\phi\\phi}$$, and compare it to the theoretical prediction for a $$\\Lambda$$CDM cosmology consistent with the \\emph{Planck} 2015 data set, finding a best-fit amplitude of $$0.95_{-0.06}^{+0.06}({\\rm Stat.})\\! _{-0.01}^{+0.01}({\\rm Sys.})$$. The null hypothesis of no lensing is rejected at a significance of $$24\\,\\sigma$$. One important use of such a lensing potential map is in cross-correlations with other dark matter tracers. We demonstrate this cross-correlation in practice by calculating the cross-spectrum, $$C_{L}^{\\phi G}$$, between the SPT+\\emph{Planck} lensing map and Wide-field Infrared Survey Explorer (\\emph{WISE}) galaxies. We fit $$C_{L}^{\\phi G}$$ to a power law of the form $$p_{L}=a(L/L_{0})^{-b}$$ with $$a=2.15 \\times 10^{-8}$$, $b=1.35$, $$L_{0}=490$$, and find $$\\eta^{\\phi G}=0.94^{+0.04}_{-0.04}$$, which is marginally lower, but in good agreement with $$\\eta^{\\phi G}=1.00^{+0.02}_{-0.01}$$, the best-fit amplitude for the cross-correlation of \\emph{Planck}-2015 CMB lensing and \\emph{WISE} galaxies over $$\\sim67\\%$$ of the sky. The lensing potential map presented here will be used for cross-correlation studies with the Dark Energy Survey (DES), whose footprint nearly completely covers the SPT $$2500\\ {\\rm deg}^2$$ field.« less

  2. A 2500 deg 2 CMB Lensing Map from Combined South Pole Telescope and Planck Data

    DOE PAGES

    Omori, Y.; Chown, R.; Simard, G.; ...

    2017-11-07

    We present a cosmic microwave background (CMB) lensing map produced from a linear combination of South Pole Telescope (SPT) and \\emph{Planck} temperature data. The 150 GHz temperature data from themore » $$2500\\ {\\rm deg}^{2}$$ SPT-SZ survey is combined with the \\emph{Planck} 143 GHz data in harmonic space, to obtain a temperature map that has a broader $$\\ell$$ coverage and less noise than either individual map. Using a quadratic estimator technique on this combined temperature map, we produce a map of the gravitational lensing potential projected along the line of sight. We measure the auto-spectrum of the lensing potential $$C_{L}^{\\phi\\phi}$$, and compare it to the theoretical prediction for a $$\\Lambda$$CDM cosmology consistent with the \\emph{Planck} 2015 data set, finding a best-fit amplitude of $$0.95_{-0.06}^{+0.06}({\\rm Stat.})\\! _{-0.01}^{+0.01}({\\rm Sys.})$$. The null hypothesis of no lensing is rejected at a significance of $$24\\,\\sigma$$. One important use of such a lensing potential map is in cross-correlations with other dark matter tracers. We demonstrate this cross-correlation in practice by calculating the cross-spectrum, $$C_{L}^{\\phi G}$$, between the SPT+\\emph{Planck} lensing map and Wide-field Infrared Survey Explorer (\\emph{WISE}) galaxies. We fit $$C_{L}^{\\phi G}$$ to a power law of the form $$p_{L}=a(L/L_{0})^{-b}$$ with $$a=2.15 \\times 10^{-8}$$, $b=1.35$, $$L_{0}=490$$, and find $$\\eta^{\\phi G}=0.94^{+0.04}_{-0.04}$$, which is marginally lower, but in good agreement with $$\\eta^{\\phi G}=1.00^{+0.02}_{-0.01}$$, the best-fit amplitude for the cross-correlation of \\emph{Planck}-2015 CMB lensing and \\emph{WISE} galaxies over $$\\sim67\\%$$ of the sky. The lensing potential map presented here will be used for cross-correlation studies with the Dark Energy Survey (DES), whose footprint nearly completely covers the SPT $$2500\\ {\\rm deg}^2$$ field.« less

  3. Farthest Neighbor: The Distant Milky Way Satellite Eridanus II

    DOE PAGES

    Li, T. S.; Simon, J. D.; Drlica-Wagner, A.; ...

    2017-03-17

    We present Magellan/IMACS spectroscopy of the recently-discovered Milky Way satellite Eridanus II (Eri II). We identify 28 member stars in Eri II, from which we measure a systemic radial velocity ofmore » $$v_{\\rm hel} = 75.6 \\pm 1.3~\\mbox{(stat.)} \\pm 2.0~\\mbox{(sys.)}~\\mathrm{km\\,s^{-1}}$$ and a velocity dispersion of $$6.9^{+1.2}_{-0.9}~\\mathrm{km\\,s^{-1}}$$. Assuming that Eri~II is a dispersion-supported system in dynamical equilibrium, we derive a mass within the half-light radius of Eri II is $$1.2^{+0.4}_{-0.3} \\times 10^{7}~\\mathrm{M_\\odot}$$, indicating a mass-to-light ratio of $$420^{+210}_{-140}~\\mathrm{M_\\odot}/\\mathrm{L_\\odot}$$ and confirming that it is a dark matter-dominated dwarf galaxy. From the equivalent width measurements of the CaT lines of 16 red giant member stars, we derive a mean metallicity of $${\\rm [Fe/H]} = -2.38 \\pm 0.13$$ and a metallicity dispersion of $$\\sigma_{\\rm [Fe/H]} = 0.47 ^{+0.12}_{-0.09}$$. The velocity of Eri II in the Galactic Standard of Rest frame is $$v_{\\rm GSR} = -66.6~\\mathrm{km\\,s^{-1}}$$, indicating that either Eri II is falling into the Milky Way potential for the first time or it has passed the apocenter of its orbit on a subsequent passage. At a Galactocentric distance of $$\\sim$$370 kpc, Eri II is one of the Milky Way's most distant satellites known. Additionally, we show that the bright blue stars previously suggested to be a young stellar population are not associated with Eri II. The lack of gas and recent star formation in Eri II is surprising given its mass and distance from the Milky Way, and may place constraints on models of quenching in dwarf galaxies and on the distribution of hot gas in the Milky Way halo. Furthermore, the large velocity dispersion of Eri II can be combined with the existence of a central star cluster to constrain MACHO dark matter with mass $$\\gtrsim10~\\mathrm{M_\\odot}$$.« less

  4. Farthest Neighbor: The Distant Milky Way Satellite Eridanus II

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

    Li, T. S.; Simon, J. D.; Drlica-Wagner, A.

    We present Magellan/IMACS spectroscopy of the recently-discovered Milky Way satellite Eridanus II (Eri II). We identify 28 member stars in Eri II, from which we measure a systemic radial velocity ofmore » $$v_{\\rm hel} = 75.6 \\pm 1.3~\\mbox{(stat.)} \\pm 2.0~\\mbox{(sys.)}~\\mathrm{km\\,s^{-1}}$$ and a velocity dispersion of $$6.9^{+1.2}_{-0.9}~\\mathrm{km\\,s^{-1}}$$. Assuming that Eri~II is a dispersion-supported system in dynamical equilibrium, we derive a mass within the half-light radius of Eri II is $$1.2^{+0.4}_{-0.3} \\times 10^{7}~\\mathrm{M_\\odot}$$, indicating a mass-to-light ratio of $$420^{+210}_{-140}~\\mathrm{M_\\odot}/\\mathrm{L_\\odot}$$ and confirming that it is a dark matter-dominated dwarf galaxy. From the equivalent width measurements of the CaT lines of 16 red giant member stars, we derive a mean metallicity of $${\\rm [Fe/H]} = -2.38 \\pm 0.13$$ and a metallicity dispersion of $$\\sigma_{\\rm [Fe/H]} = 0.47 ^{+0.12}_{-0.09}$$. The velocity of Eri II in the Galactic Standard of Rest frame is $$v_{\\rm GSR} = -66.6~\\mathrm{km\\,s^{-1}}$$, indicating that either Eri II is falling into the Milky Way potential for the first time or it has passed the apocenter of its orbit on a subsequent passage. At a Galactocentric distance of $$\\sim$$370 kpc, Eri II is one of the Milky Way's most distant satellites known. Additionally, we show that the bright blue stars previously suggested to be a young stellar population are not associated with Eri II. The lack of gas and recent star formation in Eri II is surprising given its mass and distance from the Milky Way, and may place constraints on models of quenching in dwarf galaxies and on the distribution of hot gas in the Milky Way halo. Furthermore, the large velocity dispersion of Eri II can be combined with the existence of a central star cluster to constrain MACHO dark matter with mass $$\\gtrsim10~\\mathrm{M_\\odot}$$.« less

  5. Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

    PubMed

    Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

    2012-05-01

    Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. © 2011 Blackwell Verlag GmbH.

  6. Light in condensed matter in the upper atmosphere as the origin of homochirality: circularly polarized light from Rydberg matter.

    PubMed

    Holmlid, Leif

    2009-01-01

    Clouds of the condensed excited Rydberg matter (RM) exist in the atmospheres of comets and planetary bodies (most easily observed at Mercury and the Moon), where they surround the entire bodies. Vast such clouds are recently proposed to exist in the upper atmosphere of Earth (giving rise to the enormous features called noctilucent clouds, polar mesospheric clouds, and polar mesospheric summer radar echoes). It has been shown in experiments with RM that linearly polarized visible light scattered from an RM layer is transformed to circularly polarized light with a probability of approximately 50%. The circular Rydberg electrons in the magnetic field in the RM may be chiral scatterers. The magnetic and anisotropic RM medium acts as a circular polarizer probably by delaying one of the perpendicular components of the light wave. The delay process involved is called Rabi-flopping and gives delays of the order of femtoseconds. This strong effect thus gives intense circularly polarized visible and UV light within RM clouds. Amino acids and other chiral molecules will experience a strong interaction with this light field in the upper atmospheres of planets. The interaction will vary with the stereogenic conformation of the molecules and in all probability promote the survival of one enantiomer. Here, this strong effect is proposed to be the origin of homochirality. The formation of amino acids in the RM clouds is probably facilitated by the catalytic effect of RM.

  7. Light in Condensed Matter in the Upper Atmosphere as the Origin of Homochirality: Circularly Polarized Light from Rydberg Matter

    NASA Astrophysics Data System (ADS)

    Holmlid, Leif

    2009-08-01

    Clouds of the condensed excited Rydberg matter (RM) exist in the atmospheres of comets and planetary bodies (most easily observed at Mercury and the Moon), where they surround the entire bodies. Vast such clouds are recently proposed to exist in the upper atmosphere of Earth (giving rise to the enormous features called noctilucent clouds, polar mesospheric clouds, and polar mesospheric summer radar echoes). It has been shown in experiments with RM that linearly polarized visible light scattered from an RM layer is transformed to circularly polarized light with a probability of approximately 50%. The circular Rydberg electrons in the magnetic field in the RM may be chiral scatterers. The magnetic and anisotropic RM medium acts as a circular polarizer probably by delaying one of the perpendicular components of the light wave. The delay process involved is called Rabi-flopping and gives delays of the order of femtoseconds. This strong effect thus gives intense circularly polarized visible and UV light within RM clouds. Amino acids and other chiral molecules will experience a strong interaction with this light field in the upper atmospheres of planets. The interaction will vary with the stereogenic conformation of the molecules and in all probability promote the survival of one enantiomer. Here, this strong effect is proposed to be the origin of homochirality. The formation of amino acids in the RM clouds is probably facilitated by the catalytic effect of RM.

  8. Immunodetection of the Bacteriocin Lacticin RM: Analysis of the Influence of Temperature and Tween 80 on Its Expression and Activity

    PubMed Central

    Keren, Tomer; Yarmus, Merav; Halevy, Galia; Shapira, Roni

    2004-01-01

    Immunoassays with specific antibodies offer higher sensitivity than do bioassays with indicator strains in the detection and quantification of several bacteriocins. Here we present the purification of lacticin RM and the production of specific polyclonal antibodies to a synthetic peptide resembling an internal fragment of the mature bacteriocin. The specificity and sensitivity of the generated polyclonal antibodies were evaluated in various immunoassays. The detection limits of lacticin RM were found to be 1.9, 0.16, and 0.18 μg ml−1 for Western blot, immuno-dot blot, and noncompetitive indirect enzyme-linked immunosorbent assays, respectively. Immunoassay sensitivities were 12.5-fold higher than that of the agar diffusion test (ADT). The production of lacticin RM showed temperature dependency, with 3, 4.2, 12.7, 28.9, 37.8, and 12 μg ml−1 at 37, 30, 20, 15, 10, and 4°C, respectively. Temperature-stability analysis demonstrated that lacticin RM is sensitive to mild temperature, but the loss of activity does not seem to result from protein degradation. Tween 80 increased the concentration of lacticin RM eightfold and probably affected the results of the ADT either by enhancing the activity of lacticin RM or by increasing the sensitivity of the indicator strain. The use of antibodies for the specific detection and quantification of lacticin RM can expand our knowledge of its production and stability, with important implications for further investigation and future application. PMID:15066801

  9. Reliability of Maximal Strength Testing in Novice Weightlifters

    NASA Technical Reports Server (NTRS)

    Loehr, James A.; Lee, Stuart M. C.; Feiveson, Alan H.; Ploutz-Snyder, Lori L.

    2009-01-01

    The one repetition maximum (1RM) is a criterion measure of muscle strength. However, the reliability of 1RM testing in novice subjects has received little attention. Understanding this information is crucial to accurately interpret changes in muscle strength. To evaluate the test-retest reliability of a squat (SQ), heel raise (HR), and deadlift (DL) 1RM in novice subjects. Twenty healthy males (31 plus or minus 5 y, 179.1 plus or minus 6.1 cm, 81.4 plus or minus 10.6 kg) with no weight training experience in the previous six months participated in four 1RM testing sessions, with each session separated by 5-7 days. SQ and HR 1RM were conducted using a smith machine; DL 1RM was assessed using free weights. Session 1 was considered a familiarization and was not included in the statistical analyses. Repeated measures analysis of variance with Tukey fs post-hoc tests were used to detect between-session differences in 1RM (p.0.05). Test-retest reliability was evaluated by intraclass correlation coefficients (ICC). During Session 2, the SQ and DL 1RM (SQ: 90.2 }4.3, DL: 75.9 }3.3 kg) were less than Session 3 (SQ: 95.3 }4.1, DL: 81.5 plus or minus 3.5 kg) and Session 4 (SQ: 96.6 }4.0, DL: 82.4 }3.9 kg), but there were no differences between Session 3 and Session 4. HR 1RM measured during Session 2 (150.1 }3.7 kg) and Session 3 (152.5 }3.9 kg) were not different from one another, but both were less than Session 4 (157.5 }3.8 kg). The reliability (ICC) of 1RM measures for Sessions 2-4 were 0.88, 0.83, and 0.87, for SQ, HR, and DL, respectively. When considering only Sessions 3 and 4, the reliability was 0.93, 0.91, and 0.86 for SQ, HR, and DL, respectively. One familiarization session and 2 test sessions (for SQ and DL) were required to obtain excellent reliability (ICC greater than or equal to 0.90) in 1RM values with novice subjects. We were unable to attain this level of reliability following 3 HR testing sessions therefore additional sessions may be required to obtain an ICC of greater than or equal to 0.90. Future resistive exercise studies should consider the reliability of specific measures to ensure that changes in strength with training are attributable to training and not learning effects associated with 1RM testing.

  10. Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

    PubMed Central

    Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

    2008-01-01

    We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

  11. Simulation of Nonlinear Instabilities in an Attachment-Line Boundary Layer

    NASA Technical Reports Server (NTRS)

    Joslin, Ronald D.

    1996-01-01

    The linear and the nonlinear stability of disturbances that propagate along the attachment line of a three-dimensional boundary layer is considered. The spatially evolving disturbances in the boundary layer are computed by direct numerical simulation (DNS) of the unsteady, incompressible Navier-Stokes equations. Disturbances are introduced either by forcing at the in ow or by applying suction and blowing at the wall. Quasi-parallel linear stability theory and a nonparallel theory yield notably different stability characteristics for disturbances near the critical Reynolds number; the DNS results con rm the latter theory. Previously, a weakly nonlinear theory and computations revealed a high wave-number region of subcritical disturbance growth. More recent computations have failed to achieve this subcritical growth. The present computational results indicate the presence of subcritically growing disturbances; the results support the weakly nonlinear theory. Furthermore, an explanation is provided for the previous theoretical and computational discrepancy. In addition, the present results demonstrate that steady suction can be used to stabilize disturbances that otherwise grow subcritically along the attachment line.

  12. Fetal HLA-G alleles and their effect on miscarriage.

    PubMed

    Koc, Altug; Kirbiyik, Ozgur; Kutbay, Yasar B; Ozyilmaz, Berk; Ozdemir, Taha R; Kaya, Ozge Ozer; Kubat, Gozde; Koc, Zeynep Peker

    2018-05-29

    Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels. The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date. The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing. For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation. HLA-G alleles seem to be related with miscarriage and should be considered in RM cases.

  13. Probabilistic Risk Assessment for Bone Fracture - Bone Fracture Risk Module (BFxRM)

    NASA Technical Reports Server (NTRS)

    Licata, Angelo; Myers, Jerry G.; Lewandowski, Beth

    2013-01-01

    This presentation summarizes the concepts, development, and application of NASA's Bone Fracture Risk Module (BFxRM). The overview includes an assessmnet of strenghts and limitations of the BFxRM and proposes a numebr of discussion questions to the panel regarding future development avenues for this simulation system.

  14. 40 CFR 725.60 - Withdrawal of submission by the submitter.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., OPPT Document Control Office (DCO), EPA East Bldg., 1201 Constitution Ave., NW., Rm. 6428, Washington... Control Office (DCO), EPA East Bldg., 1201 Constitution Ave., NW., Rm. 6428, Washington, DC 20004. (ii... Document Control Office (DCO), EPA East Bldg., 1201 Constitution Ave., NW., Rm. 6428, Washington, DC 20004...

  15. Effects of ΛΛ ‑ ΞN mixing in the decay of {}_{{\\rm{\\Lambda }}{\\rm{\\Lambda }}}{}^{6}{\\rm{H}}{\\rm{e}}

    NASA Astrophysics Data System (ADS)

    Maneu, J.; Parreño, A.; Ramos, A.

    2018-05-01

    A one-meson exchange model including the ground state of the pseudoscalar octet is used to describe the weak two-body interactions responsible for the decay of {}{{Λ }{{Λ }}}{}6{{H}}{{e}}. Strong interaction effects are taken into account by a microscopic study based on the solution of G-matrix and T-matrix equations for the initial and final interacting pairs respectively. Results for the decay induced by {{Λ }}{{Λ }}\\to {{Λ }}N({{Σ }}N) transitions are given.

  16. Risk Management Interventions to Reduce Injuries and Maximize Economic Benefits in U.S. Mining.

    PubMed

    Griffin, Stephanie C; Bui, David P; Gowrisankaran, Gautam; Lutz, Eric A; He, Charles; Hu, Chengcheng; Burgess, Jefferey L

    2018-03-01

    Risk management (RM) is a cyclical process of identifying and ranking risks, implementing controls, and evaluating their effectiveness. This study aims to identify effective RM interventions in the U.S. mining industry. RM interventions were identified in four companies representing metal, aggregate, and coal mining sectors. Injury rates were determined using Mine Safety and Health Administration (MSHA) data and changes in injury rates identified through change point analysis. Program implementation costs and associated changes in injury costs were evaluated for select interventions. Six of 20 RM interventions were associated with a decline in all injuries and one with a reduction in lost-time injuries, all with a positive return on investment. Reductions in injuries and associated costs were observed following implementation of a limited number of specific RM interventions.

  17. Differential cross sections for excitation of H 2 by low-energy electron impact

    DOE PAGES

    Hargreaves, Leigh R.; Bhari, S.; Adjari, B.; ...

    2017-10-31

    Experimental and theoretical differential cross sections (DCS) for the electron-impact excitation of molecular hydrogen to themore » $$B{}^{1}{{\\rm{\\Sigma }}}_{u}^{+}$$, $$c{}^{3}{{\\rm{\\Pi }}}_{u}$$, $$a{}^{3}{{\\rm{\\Sigma }}}_{g}^{+}$$, $$C{}^{1}{{\\rm{\\Pi }}}_{u}$$, and the $$E(F){}^{1}{{\\rm{\\Sigma }}}_{g}^{+}$$ states are presented at incident energies near to threshold. The experimental DCSs were taken at incident energies of 14, 15, 16 and 17.5 eV and for scattering angles from 10° to 130°. In conclusion, the theoretical DCSs are from the convergent close-coupling method which has recently successfully modeled differential electron scattering from H 2 when compared with available experiment at energies of 17.5 eV and above.« less

  18. Differential cross sections for excitation of H 2 by low-energy electron impact

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

    Hargreaves, Leigh R.; Bhari, S.; Adjari, B.

    Experimental and theoretical differential cross sections (DCS) for the electron-impact excitation of molecular hydrogen to themore » $$B{}^{1}{{\\rm{\\Sigma }}}_{u}^{+}$$, $$c{}^{3}{{\\rm{\\Pi }}}_{u}$$, $$a{}^{3}{{\\rm{\\Sigma }}}_{g}^{+}$$, $$C{}^{1}{{\\rm{\\Pi }}}_{u}$$, and the $$E(F){}^{1}{{\\rm{\\Sigma }}}_{g}^{+}$$ states are presented at incident energies near to threshold. The experimental DCSs were taken at incident energies of 14, 15, 16 and 17.5 eV and for scattering angles from 10° to 130°. In conclusion, the theoretical DCSs are from the convergent close-coupling method which has recently successfully modeled differential electron scattering from H 2 when compared with available experiment at energies of 17.5 eV and above.« less

  19. Vortex wakes of a flapping foil in a flowing soap film

    NASA Astrophysics Data System (ADS)

    Schnipper, Teis; Andersen, Anders; Bohr, Tomas

    2008-11-01

    We present an experimental study of an oscillating, symmetric foil in a vertically flowing soap film. By varying frequency and amplitude of the oscillation we explore and visualize a variety of wake structures, including von Kármán wake, reverse von Kármán wake, 2P wake, and 2P+2S wake. We characterize the transition from the von Kármán wake (drag) to the reverse von Kármán wake (thrust) and discuss the results in relation to fish swimming. We visualize the time evolution of the vortex shedding in detail, identify the origins of the vortices comprising the wake, and propose a simple model to account for the transition from von Kármán like wakes to more exotic wake structures.

  20. Using the Inflection Points and Rates of Growth and Decay to Predict Levels of Solar Activity

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.; Hathaway, David H.

    2008-01-01

    The ascending and descending inflection points and rates of growth and decay at specific times during the sunspot cycle are examined as predictors for future activity. On average, the ascending inflection point occurs about 1-2 yr after sunspot minimum amplitude (Rm) and the descending inflection point occurs about 6-7 yr after Rm. The ascending inflection point and the inferred slope (including the 12-mo moving average (12-mma) of (Delta)R (the month-to-month change in the smoothed monthly mean sunspot number (R)) at the ascending inflection point provide strong indications as to the expected size of the ongoing cycle s sunspot maximum amplitude (RM), while the descending inflection point appears to provide an indication as to the expected length of the ongoing cycle. The value of the 12-mma of (Delta)R at elapsed time T = 27 mo past the epoch of RM (E(RM)) seems to provide a strong indication as to the expected size of Rm for the following cycle. The expected Rm for cycle 24 is 7.6 +/- 4.4 (the 90-percent prediction interval), occurring before September 2008. Evidence is also presented for secular rises in selected cycle-related parameters and for preferential grouping of sunspot cycles by amplitude and/or period.

  1. Do service users with intellectual disabilities want to be involved in the risk management process? A thematic analysis.

    PubMed

    Kilcommons, Aoiffe M; Withers, Paul; Moreno-Lopez, Águeda

    2012-09-01

    Involving ID service users in risk decision making necessitates consideration of an individual's ability to assess the implications and associated risks and thus make an informed choice. This calls for research on service users' awareness and understanding of risk management (RM). Thirteen people in a residential ID service who were reviewed under the risk management process (RMP) participated in the research. Thematic analysis explored participants' knowledge and understanding of risk management to establish ability to make informed choice. Two main meta-themes (lack of awareness about RM and awareness about RM) and four meta-themes (extent of RM awareness, locus of control, compliance and empowerment) emerged. Nine of 13 participants demonstrated some knowledge and awareness of RM and wanted to contribute to the RMP, despite not being consulted about or given the opportunity to be involved in RM. The majority of service users in this sample had some awareness of the purpose of RM and could make partially informed decisions about whether they would like to be involved in the RMP. The findings highlight the need for professionals to actively attempt to involve ID service users in the management of their own risk. © 2012 Blackwell Publishing Ltd.

  2. Comparative analyses of animal-tracking data reveal ecological significance of endothermy in fishes

    PubMed Central

    Watanabe, Yuuki Y.; Goldman, Kenneth J.; Caselle, Jennifer E.; Chapman, Demian D.; Papastamatiou, Yannis P.

    2015-01-01

    Despite long evolutionary separations, several sharks and tunas share the ability to maintain slow-twitch, aerobic red muscle (RM) warmer than ambient water. Proximate causes of RM endothermy are well understood, but ultimate causes are unclear. Two advantages often proposed are thermal niche expansion and elevated cruising speeds. The thermal niche hypothesis is generally supported, because fishes with RM endothermy often exhibit greater tolerance to broad temperature ranges. In contrast, whether fishes with RM endothermy cruise faster, and achieve any ecological benefits from doing so, remains unclear. Here, we compiled data recorded by modern animal-tracking tools for a variety of free-swimming marine vertebrates. Using phylogenetically informed allometry, we show that both cruising speeds and maximum annual migration ranges of fishes with RM endothermy are 2–3 times greater than fishes without it, and comparable to nonfish endotherms (i.e., penguins and marine mammals). The estimated cost of transport of fishes with RM endothermy is twice that of fishes without it. We suggest that the high energetic cost of RM endothermy in fishes is offset by the benefit of elevated cruising speeds, which not only increase prey encounter rates, but also enable larger-scale annual migrations and potentially greater access to seasonally available resources. PMID:25902489

  3. Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

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

    Aad, G.

    2014-11-04

    This article presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy ofmore » $$\\sqrt{s}=7\\;{\\rm Te}{\\rm V}$$ and correspond to an integrated luminosity of $$4.6\\;{\\rm f}{{{\\rm b}}^{-1}}$$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum $${{p}_{{\\rm T}}}\\gt 320\\;{\\rm Ge}{\\rm V}$$ and pseudorapidity $$|\\eta |\\lt 1.9$$, is measured to be $${{\\sigma }_{W+Z}}=8.5\\pm 1.7$$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques.« less

  4. Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice.

    PubMed

    Broussard, John I; Acion, Laura; De Jesús-Cortés, Héctor; Yin, Terry; Britt, Jeremiah K; Salas, Ramiro; Costa-Mattioli, Mauro; Robertson, Claudia; Pieper, Andrew A; Arciniegas, David B; Jorge, Ricardo

    2018-01-01

    Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour. We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group. We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry. RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour. rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

  5. The Growth and Characterization of the Bismuth Strontium-Calcium 2212 Superconductor

    NASA Astrophysics Data System (ADS)

    Moulton, Linda Vidale

    A miniaturized float zone technique, sometimes referred to as the Laser-heated Pedestal Growth (LHPG) method, was used to produce high quality crystals of the incongruently melting rm Bi_2Sr_2CaCu _2O_{8+delta} (2212) superconductor. The main focus of this research was to (1) produce superconducting samples having different compositions, (2) identify the melt compositions and growth temperatures which produced these samples, and (3) determine the variation of their superconducting transition temperature (T _{rm C}) with composition and processing conditions. The rm Bi_2(Sr,Ca) _3Cu_2O_{8+delta} crystallization experiments were supplemented by a series of similar experiments on the incongruently melting compound rm Ca_3Al_2O_6. The phase equilibria in the CaO-rm Al_2O _3 system has been thoroughly studied, and by analyzing the float-zone growth of this simpler and better-characterized material, it was verified that phase equilibria information and solidification behavior could be extracted from and explained by these solidification experiments. Two different types of nonplanar, crystal/melt interface morphologies were observed in the rm Ca_3Al_2O_6 experiments. Each reflected the influence of the phase equilibria in the CaO-rm Al_2O_3 system and component segregation in the melt. The molten zone compositions were found to approach those predicted by the CaO-rm Al_2O_3 phase diagram as the growth rate decreased, in accordance with the Burton-Prim Slichter relationship. Excellent agreement was obtained between actual phases found to coexist at the rm Ca_3Al_2O_6 /melt interface and the predictions of classical crystal growth theory. Based on the results of the rm Ca _3Al_2O_6 crystallization study, the crystal/melt equilibria in the far more complex rm Bi_2O_3-SrO-CaO-CuO system was evaluated by determining the phases formed during the superconductor growth experiments. The melt compositions were found to be rm Bi_2O_3 -rich and SrO-poor relative to the compositions of the 2212 crystals grown from them. The CaO and CuO segregation coefficients, on the other hand, were observed to be near unity. As one would expect for an incongruently -melting compound, segregation at the solidification front generally decreased with increasing crystallization temperature, but all the segregation coefficients were not observed to simultaneously approach unity. The superconducting transition temperatures (T _{rm C}'s) of six as-crystallized samples having homogeneous crystal compositions were also measured. Sample T_{rm C} was observed to increase with increasing growth temperature and, therefore, change with crystal composition. The results of this study suggested that it is desirable to grow crystals at the highest possible crystallization temperature since they will: (1) have the highest as-grown T_{rm C} 's, and (2) solidify with the least component segregation at the growth interface. In addition, the analysis presented here suggests that such growth is not recommended at higher growth rates, since crystals with mid-range solidus compositions (and consequently, moderate growth temperatures) should crystallize most reliably as single-phase samples at higher growth rates.

  6. Association mapping for yield and grain quality traits in rice (Oryza sativa L.)

    PubMed Central

    2010-01-01

    Association analysis was applied to a panel of accessions of Embrapa Rice Core Collection (ERiCC) with 86 SSR and field data from two experiments. A clear subdivision between lowland and upland accessions was apparent, thereby indicating the presence of population structure. Thirty-two accessions with admixed ancestry were identified through structure analysis, these being discarded from association analysis, thus leaving 210 accessions subdivided into two panels. The association of yield and grain-quality traits with SSR was undertaken with a mixed linear model, with markers and subpopulation as fixed factors, and kinship matrix as a random factor. Eight markers from the two appraised panels showed significant association with four different traits, although only one (RM190) maintained the marker-trait association across years and cultivation. The significant association detected between amylose content and RM190 was in agreement with previous QTL analyses in the literature. Herein, the feasibility of undertaking association analysis in conjunction with germplasm characterization was demonstrated, even when considering low marker density. The high linkage disequilibrium expected in rice lines and cultivars facilitates the detection of marker-trait associations for implementing marker assisted selection, and the mining of alleles related to important traits in germplasm. PMID:21637426

  7. Cost-effectiveness of HPV vaccination in the prevention of cervical cancer in Malaysia.

    PubMed

    Ezat, Wan Puteh Sharifa; Aljunid, Syed

    2010-01-01

    Cervical cancers (CC) demonstrate the second highest incidence of female cancers in Malaysia. The costs of chronic management have a high impact on nation's health cost and patient's quality of life that can be avoided by better screening and HPV vaccination. Respondents were interviewed from six public Gynecology-Oncology hospitals. Methods include experts' panel discussions to estimate treatment costs by severity and direct interviews with respondents using costing and SF-36 quality of life (QOL) questionnaires. Three options were compared i.e. screening via Pap smear; quadrivalent HPV Vaccination and combined strategy (screening plus vaccination). Scenario based sensitivity analysis using screening population coverage (40-80%) and costs of vaccine (RM 300-400/dose) were calculated. 502 cervical pre invasive and invasive cervical cancer (ICC) patients participated in the study. Mean age was 53.3 +/- 11.2 years, educated till secondary level (39.4%), Malays (44.2%) and married for 27.73 +/- 12.1 years. Life expectancy gained from vaccination is 13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated. Cost/QALYs for Pap smear at base case is RM 1,214.96/QALYs and RM 1,100.01 at increased screening coverage; for HPV Vaccination base case is at RM 35,346.79 and RM 46,530.08 when vaccination price is higher. In combined strategy, base case is RM 11,289.58; RM 7,712.74 at best case and RM 14,590.37 at worst case scenario. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher is highly cost effective at RM 946.74 per QALYs saved and this is followed by combined strategy at RM 35,346.67 per QALYs saved. Vaccination increase life expectancy with better QOL of women when cancer can be avoided. Cost effective strategies will include increasing the Pap smear coverage to 70% or higher. Since feasibility and long term screening adherence is doubtful among Malaysian women, vaccination of young women is a more cost effective strategy against cervical cancers.

  8. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+ TEM and CD8+ TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.

    PubMed

    Srivastava, Ruchi; Khan, Arif A; Chilukuri, Sravya; Syed, Sabrina A; Tran, Tien T; Furness, Julie; Bahraoui, Elmostafa; BenMohamed, Lbachir

    2017-07-15

    Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 + T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 + T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 + T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 + CD8 + T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 -/- or CXCR3 -/- deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 -/- mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 + T cells (T EM ) and tissue-resident memory CD8 + T cells (T RM ), but not of central memory CD8 + T cells (T CM ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 -/- deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 + T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. IMPORTANCE We determined how the CXCL10/CXCR3 pathway affects CD8 + T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 + T EM and CD8 + T RM cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 + T EM and CD8 + T RM cells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed. Copyright © 2017 American Society for Microbiology.

  9. Multilaboratory trial for determination of ceftiofur residues in bovine and swine kidney and muscle, and bovine milk.

    PubMed

    Hornish, Rex E; Hamlow, Philip J; Brown, Scott A

    2003-01-01

    A multilaboratory trial for determining ceftiofur-related residues in bovine and swine kidney and muscle, and bovine milk was conducted following regulatory guidelines of the U.S. Food and Drug Administration, Center for Veterinary Medicine. The methods convert all desfuroylceftiofur-related residues containing the intact beta-lactam ring to desfuroylceftiofur acetamide to establish ceftiofur residues in tissues. Four laboratories analyzed 5 sets of samples for each tissue. Each sample set consisted of a control/blank sample and 3 control samples fortified with ceftiofur at 0.5 Rm, Rm, and 2 Rm, respectively, where Rm is the U.S. tolerance assigned for ceftiofur residue in each tissue/matrix: 0.100 microg/mL for milk, 8.0 microg/g for kidney (both species), 1.0 microg/g for bovine muscle, and 2.0 microg/g for swine muscle. Each sample set also contained 2 samples of incurred-residue tissues (one > Rm and one < Rm) from animals treated with ceftiofur hydrochloride. All laboratories completed the method trial after a familiarization phase and test of system suitability in which they demonstrated > 80% recovery in pretrial fortified test samples. Results showed that the methods met all acceptable performance criteria for recovery, accuracy, and precision. Although sample preparation was easy, solid-phase extraction cartridge performance must be carefully evaluated before samples are processed. The liquid chromatography detection system was easily set up; however, the elution profile may require slight modifications. The procedures could clearly differentiate between violative (> Rm) and nonviolative (< Rm) ceftiofur residues. Participating laboratories found the procedures suitable for ceftiofur residue determination.

  10. Influence of the pH on the accumulation of phosphate by red mud (a bauxite ore processing waste).

    PubMed

    Castaldi, Paola; Silvetti, Margherita; Garau, Giovanni; Deiana, Salvatore

    2010-10-15

    In the present work we investigated the interactions established between red mud (RM) and phosphate anions (P) at pH 4.0, 7.0 and 10.0. The amount of P sorbed by RM (P-RM) increased as the pH decreased being equal to 4.871 mmol g(-1) at pH 4.0, 0.924 mmol g(-1) at pH 7.0, and 0.266 mmol g(-1) at pH 10.0. Sequential extractions' data of P-RM equilibrated at pH 4.0 and 7.0, suggested that the phosphate sorption at these pH values was mainly regulated by two different mechanisms that gave rise to a chemical adsorption on RM phases, and to the formation of metal phosphate precipitates. By contrast, at pH 10.0 the P-sorption was regulated by a chemisorption mechanism on Fe-Al phases of RM. These findings were supported by FT-IR analysis, which showed a broad band at 1114 and 1105 cm(-1) in P-RM spectra at pH 4.0 and 7.0 respectively, attributable to P-O(H) stretching nu(3)-modes associated to inner-sphere complexes of phosphate on Fe-Al phases, or alternatively to stretching vibrations of PO(4)(3-) tetrahedra, arising from a precipitate of aluminium phosphate. Importantly, the FT-IR spectroscopy showed a phosphate-promoted dissolution of tectosilicates, notably cancrinite and sodalite, in RM exchanged with phosphate at pH 4.0 and 7.0. 2010 Elsevier B.V. All rights reserved.

  11. Association Between Maximal Bench Press Strength and Isometric Handgrip Strength Among Breast Cancer Survivors.

    PubMed

    Rogers, Benjamin H; Brown, Justin C; Gater, David R; Schmitz, Kathryn H

    2017-02-01

    To characterize the relationship between 1-repetition maximum (1-RM) bench press strength and isometric handgrip strength among breast cancer survivors. Cross-sectional study. Laboratory. Community-dwelling breast cancer survivors (N=295). Not applicable. 1-RM bench press strength was measured with a barbell and exercise bench. Isometric handgrip strength was measured using an isometric dynamometer, with 3 maximal contractions of the left and right hands. All measures were conducted by staff with training in clinical exercise testing. Among 295 breast cancer survivors, 1-RM bench press strength was 18.2±6.1kg (range, 2.2-43.0kg), and isometric handgrip strength was 23.5±5.8kg (range, 9.0-43.0kg). The strongest correlate of 1-RM bench press strength was the average isometric handgrip strength of both hands (r=.399; P<.0001). Mean difference analysis suggested that the average isometric handgrip strength of both hands overestimated 1-RM bench press strength by 4.7kg (95% limits of agreement, -8.2 to 17.6kg). In a multivariable linear regression model, the average isometric handgrip strength of both hands (β=.31; P<.0001) and age (β=-.20; P<.0001) were positively correlated with 1-RM bench press strength (R 2 =.23). Isometric handgrip strength is a poor surrogate for 1-RM bench press strength among breast cancer survivors. 1-RM bench press strength and isometric handgrip strength quantify distinct components of muscular strength. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  12. Functional and real-time requirements of a multisensor data fusion (MSDF) situation and threat assessment (STA) resource management (RM) system

    NASA Astrophysics Data System (ADS)

    Duquet, Jean Remi; Bergeron, Pierre; Blodgett, Dale E.; Couture, Jean; Macieszczak, Maciej; Mayrand, Michel; Chalmers, Bruce A.; Paradis, Stephane

    1998-03-01

    The Research and Development group at Lockheed Martin Canada, in collaboration with the Defence Research Establishment Valcartier, has undertaken a research project in order to capture and analyze the real-time and functional requirements of a next generation Command and Control System (CCS) for the Canadian Patrol Frigates, integrating Multi- Sensor Data Fusion (MSDF), Situation and Threat Assessment (STA) and Resource Management (RM). One important aspect of the project is to define how the use of Artificial Intelligence may optimize the performance of an integrated, real-time MSDF/STA/RM system. A closed-loop simulation environment is being developed to facilitate the evaluation of MSDF/STA/RM concepts, algorithms and architectures. This environment comprises (1) a scenario generator, (2) complex sensor, hardkill and softkill weapon models, (3) a real-time monitoring tool, (4) a distributed Knowledge-Base System (KBS) shell. The latter is being completely redesigned and implemented in-house since no commercial KBS shell could adequately satisfy all the project requirements. The closed- loop capability of the simulation environment, together with its `simulated real-time' capability, allows the interaction between the MSDF/STA/RM system and the environment targets during the execution of a scenario. This capability is essential to measure the performance of many STA and RM functionalities. Some benchmark scenarios have been selected to demonstrate quantitatively the capabilities of the selected MSDF/STA/RM algorithms. The paper describes the simulation environment and discusses the MSDF/STA/RM functionalities currently implemented and their performance as an automatic CCS.

  13. Trunk muscle activation during dynamic weight-training exercises and isometric instability activities.

    PubMed

    Hamlyn, Nicolle; Behm, David G; Young, Warren B

    2007-11-01

    The purpose of this study was to examine the extent of activation in various trunk muscles during dynamic weight-training and isometric instability exercises. Sixteen subjects performed squats and deadlifts with 80% 1 repetition maximum (1RM), as well as with body weight as resistance and 2 unstable calisthenic-type exercises (superman and sidebridge). Electromyographic (EMG) activity was measured from the lower abdominals (LA), external obliques (EO), upper lumbar erector spinae (ULES), and lumbar-sacral erector spinae (LSES) muscle groups. Results indicated that the LSES EMG activity during the 80% 1RM squat significantly exceeded 80% 1RM deadlift LSES EMG activity by 34.5%. The LSES EMG activity of the 80% 1RM squat also exceeded the body weight squat, deadlift, superman, and sidebridge by 56, 56.6, 65.5, and 53.1%, respectively. The 80% 1RM deadlift ULES EMG activity significantly exceeded the 80% 1RM squat exercise by 12.9%. In addition, the 80% 1RM deadlift ULES EMG activity also exceeded the body weight squat, deadlift, superman, and sidebridge exercises by 66.7, 65.5, 69.3, and 68.6%, respectively. There were no significant changes in EO or LA activity. Therefore, the augmented activity of the LSES and ULES during 80% 1RM squat and deadlift resistance exercises exceeded the activation levels achieved with the same exercises performed with body weight and selected instability exercises. Individuals performing upright, resisted, dynamic exercises can achieve high trunk muscle activation and thus may not need to add instability device exercises to augment core stability training.

  14. Salivary hormone and immune responses to three resistance exercise schemes in elite female athletes.

    PubMed

    Nunes, João A; Crewther, Blair T; Ugrinowitsch, Carlos; Tricoli, Valmor; Viveiros, Luís; de Rose, Dante; Aoki, Marcelo S

    2011-08-01

    This study examined the salivary hormone and immune responses of elite female athletes to 3 different resistance exercise schemes. Fourteen female basketball players each performed an endurance scheme (ES-4 sets of 12 reps, 60% of 1 repetition maximum (1RM) load, 1-minute rest periods), a strength-hypertrophy scheme (SHS-1 set of 5RM, 1 set of 4RM, 1 set of 3RM, 1 set of 2RM, and 1set of 1RM with 3-minute rest periods, followed by 3 sets of 10RM with 2-minute rest periods) and a power scheme (PS-3 sets of 10 reps, 50% 1RM load, 3-minute rest periods) using the same exercises (bench press, squat, and biceps curl). Saliva samples were collected at 07:30 hours, pre-exercise (Pre) at 09:30 hours, postexercise (Post), and at 17:30 hours. Matching samples were also taken on a nonexercising control day. The samples were analyzed for testosterone, cortisol (C), and immunoglobulin A concentrations. The total volume of load lifted differed among the 3 schemes (SHS > ES > PS, p < 0.05). Postexercise C concentrations increased after all schemes, compared to control values (p < 0.05). In the SHS, the postexercise C response was also greater than pre-exercise data (p < 0.05). The current findings confirm that high-volume resistance exercise schemes can stimulate greater C secretion because of higher metabolic demand. In terms of practical applications, acute changes in C may be used to evaluate the metabolic demands of different resistance exercise schemes, or as a tool for monitoring training strain.

  15. Impact of Different Ventilation Strategies on Driving Pressure, Mechanical Power, and Biological Markers During Open Abdominal Surgery in Rats.

    PubMed

    Maia, Lígia de A; Samary, Cynthia S; Oliveira, Milena V; Santos, Cintia L; Huhle, Robert; Capelozzi, Vera L; Morales, Marcelo M; Schultz, Marcus J; Abreu, Marcelo G; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia Rieken Macedo

    2017-10-01

    Intraoperative mechanical ventilation may yield lung injury. To date, there is no consensus regarding the best ventilator strategy for abdominal surgery. We aimed to investigate the impact of the mechanical ventilation strategies used in 2 recent trials (Intraoperative Protective Ventilation [IMPROVE] trial and Protective Ventilation using High versus Low PEEP [PROVHILO] trial) on driving pressure (ΔPRS), mechanical power, and lung damage in a model of open abdominal surgery. Thirty-five Wistar rats were used, of which 28 were anesthetized, and a laparotomy was performed with standardized bowel manipulation. Postoperatively, animals (n = 7/group) were randomly assigned to 4 hours of ventilation with: (1) tidal volume (VT) = 7 mL/kg and positive end-expiratory pressure (PEEP) = 1 cm H2O without recruitment maneuvers (RMs) (low VT/low PEEP/RM-), mimicking the low-VT/low-PEEP strategy of PROVHILO; (2) VT = 7 mL/kg and PEEP = 3 cm H2O with RMs before laparotomy and hourly thereafter (low VT/moderate PEEP/4 RM+), mimicking the protective ventilation strategy of IMPROVE; (3) VT = 7 mL/kg and PEEP = 6 cm H2O with RMs only before laparotomy (low VT/high PEEP/1 RM+), mimicking the strategy used after intubation and before extubation in PROVHILO; or (4) VT = 14 mL/kg and PEEP = 1 cm H2O without RMs (high VT/low PEEP/RM-), mimicking conventional ventilation used in IMPROVE. Seven rats were not tracheotomized, operated, or mechanically ventilated, and constituted the healthy nonoperated and nonventilated controls. Low VT/moderate PEEP/4 RM+ and low VT/high PEEP/1 RM+, compared to low VT/low PEEP/RM- and high VT/low PEEP/RM-, resulted in lower ΔPRS (7.1 ± 0.8 and 10.2 ± 2.1 cm H2O vs 13.9 ± 0.9 and 16.9 ± 0.8 cm H2O, respectively; P< .001) and less mechanical power (63 ± 7 and 79 ± 20 J/min vs 110 ± 10 and 120 ± 20 J/min, respectively; P = .007). Low VT/high PEEP/1 RM+ was associated with less alveolar collapse than low VT/low PEEP/RM- (P = .03). E-cadherin expression was higher in low VT/moderate PEEP/4 RM+ than in low VT/low PEEP/RM- (P = .013) or high VT/low PEEP/RM- (P = .014). The extent of alveolar collapse, E-cadherin expression, and tumor necrosis factor-alpha correlated with ΔPRS (r = 0.54 [P = .02], r = -0.48 [P = .05], and r = 0.59 [P = .09], respectively) and mechanical power (r = 0.57 [P = .02], r = -0.54 [P = .02], and r = 0.48 [P = .04], respectively). In this model of open abdominal surgery based on the mechanical ventilation strategies used in IMPROVE and PROVHILO trials, lower mechanical power and its surrogate ΔPRS were associated with reduced lung damage.

  16. Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments.

    PubMed Central

    Solomon, Aharon; Bandhakavi, Sricharan; Jabbar, Sean; Shah, Rena; Beitel, Greg J; Morimoto, Richard I

    2004-01-01

    The molecular mechanisms that enable multicellular organisms to sense and modulate their responses to hyperosmotic environments are poorly understood. Here, we employ Caenorhabditis elegans to characterize the response of a multicellular organism to osmotic stress and establish a genetic screen to isolate mutants that are osmotic stress resistant (OSR). In this study, we describe the cloning of a novel gene, osr-1, and demonstrate that it regulates osmosensation, adaptation, and survival in hyperosmotic environments. Whereas wild-type animals exposed to hyperosmotic conditions rapidly lose body volume, motility, and viability, osr-1(rm1) mutant animals maintain normal body volume, motility, and viability even upon chronic exposures to high osmolarity environments. In addition, osr-1(rm1) animals are specifically resistant to osmotic stress and are distinct from previously characterized osmotic avoidance defective (OSM) and general stress resistance age-1(hx546) mutants. OSR-1 is expressed in the hypodermis and intestine, and expression of OSR-1 in hypodermal cells rescues the osr-1(rm1) phenotypes. Genetic epistasis analysis indicates that OSR-1 regulates survival under osmotic stress via CaMKII and a conserved p38 MAP kinase signaling cascade and regulates osmotic avoidance and resistance to acute dehydration likely by distinct mechanisms. We suggest that OSR-1 plays a central role in integrating stress detection and adaptation responses by invoking multiple signaling pathways to promote survival under hyperosmotic environments. PMID:15166144

  17. Complete genome sequence of salmonella enterica subsp. enterica Serovar Thompson Strain RM6836

    USDA-ARS?s Scientific Manuscript database

    Salmonella enterica subsp. enterica serovar Thompson (S. Thompson) strain RM6836 was isolated from lettuce in 2002. We report the complete sequence and annotation of the genome of S. Thompson strain RM6836. This is the first reported complete genome sequence for S. Thompson and will provide a point ...

  18. Using conjoint analysis to measure the acceptability of rectal microbicides among men who have sex with men in four South American cities.

    PubMed

    Kinsler, Janni J; Cunningham, William E; Nureña, César R; Nadjat-Haiem, Carsten; Grinsztejn, Beatriz; Casapia, Martin; Montoya-Herrera, Orlando; Sánchez, Jorge; Galea, Jerome T

    2012-08-01

    Conjoint Analysis (CJA), a statistical market-based technique that assesses the value consumers place on product characteristics, may be used to predict acceptability of hypothetical products. Rectal Microbicides (RM)-substances that would prevent HIV infection during receptive anal intercourse-will require acceptability data from potential users in multiple settings to inform the development process by providing valuable information on desirable product characteristics and issues surrounding potential barriers to product use. This study applied CJA to explore the acceptability of eight different hypothetical RM among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro, Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio. Product effectiveness had the greatest impact on acceptability in all four cities, but the impact of other product characteristics varied by city. This study demonstrates that MSM from the same region but from different cities place different values on RM characteristics that could impact uptake of an actual RM. Understanding specific consumer preferences is crucial during RM product development, clinical trials and eventual product dissemination.

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

    Yan, F.; Zhao, G.; Fosbury, R. A. E.

    Due to stellar rotation, the observed radial velocity of a star varies during the transit of a planet across its surface, a phenomenon known as the Rossiter–McLaughlin (RM) effect. The amplitude of the RM effect is related to the radius of the planet which, because of differential absorption in the planetary atmosphere, depends on wavelength. Therefore, the wavelength-dependent RM effect can be used to probe the planetary atmosphere. We measure for the first time the RM effect of the Earth transiting the Sun using a lunar eclipse observed with the ESO High Accuracy Radial velocity Planet Searcher spectrograph. We analyzemore » the observed RM effect at different wavelengths to obtain the transmission spectrum of the Earth’s atmosphere after the correction of the solar limb-darkening and the convective blueshift. The ozone Chappuis band absorption as well as the Rayleigh scattering features are clearly detectable with this technique. Our observation demonstrates that the RM effect can be an effective technique for exoplanet atmosphere characterization. Its particular asset is that photometric reference stars are not required, circumventing the principal challenge for transmission spectroscopy studies of exoplanet atmospheres using large ground-based telescopes.« less

  20. Remote Monitoring for Follow-up of Patients with Cardiac Implantable Electronic Devices

    PubMed Central

    Morichelli, Loredana; Varma, Niraj

    2014-01-01

    Follow-up of patients with cardiac implantable electronic devices is challenging due to the increasing number and technical complexity of devices coupled to increasing clinical complexity of patients. Remote monitoring (RM) offers the opportunity to optimise clinic workflow and to improve device monitoring and patient management. Several randomised clinical trials and registries have demonstrated that RM may reduce number of hospital visits, time required for patient follow-up, physician and nurse time, hospital and social costs. Furthermore, patient retention and adherence to follow-up schedule are significantly improved by RM. Continuous wireless monitoring of data stored in the device memory with automatic alerts allows early detection of device malfunctions and of events requiring clinical reaction, such as atrial fibrillation, ventricular arrhythmias and heart failure. Early reaction may improve patient outcome. RM is easy to use and patients showed a high level of acceptance and satisfaction. Implementing RM in daily practice may require changes in clinic workflow. To this purpose, new organisational models have been introduced. In spite of a favourable cost:benefit ratio, RM reimbursement still represents an issue in several European countries. PMID:26835079

  1. Reproducibility of tumor motion probability distribution function in stereotactic body radiation therapy of lung cancer.

    PubMed

    Zhang, Fan; Hu, Jing; Kelsey, Chris R; Yoo, David; Yin, Fang-Fang; Cai, Jing

    2012-11-01

    To evaluate the reproducibility of tumor motion probability distribution function (PDF) in stereotactic body radiation therapy (SBRT) of lung cancer using cine megavoltage (MV) images. Cine MV images of 20 patients acquired during three-dimensional conformal (6-11 beams) SBRT treatments were retrospectively analyzed to extract tumor motion trajectories. For each patient, tumor motion PDFs were generated per fraction (PDF(n)) using three selected "usable" beams. Patients without at least three usable beams were excluded from the study. Fractional PDF reproducibility (R(n)) was calculated as the Dice similarity coefficient between PDF(n) to a "ground-truth" PDF (PDF(g)), which was generated using the selected beams of all fractions. The mean of R(n), labeled as R(m), was calculated for each patient and correlated to the patient's mean tumor motion rang (A(m)). Change of R(m) during the course of SBRT treatments was also evaluated. Intra- and intersubject coefficient of variation (CV) of R(m) and A(m) were determined. Thirteen patients had at least three usable beams and were analyzed. The mean of R(m) was 0.87 (range, 0.84-0.95). The mean of A(m) was 3.18 mm (range, 0.46-7.80 mm). R(m) was found to decrease as A(m) increases following an equation of R(m) = 0.17e(-0.9Am) + 0.84. R(m) also decreased slightly throughout the course of treatments. Intersubject CV of R(m) (0.05) was comparable to intrasubject CV of R(m) (range, 0.02-0.09); intersubject CV of A(m) (0.73) was significantly greater than intrasubject CV of A(m) (range, 0.09-0.24). Tumor motion PDF can be determined using cine MV images acquired during the treatments. The reproducibility of lung tumor motion PDF decreased exponentially as the tumor motion range increased and decreased slightly throughout the course of the treatments. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Parental Restriction of Mature-rated Media and Its Association With Substance Use Among Argentinean Adolescents.

    PubMed

    Mejia, Raul; Pérez, Adriana; Peña, Lorena; Morello, Paola; Kollath-Cattano, Christy; Braun, Sandra; Thrasher, James F; Sargent, James D

    2016-04-01

    To assess the independent relation between parental restrictions on mature-rated media (M-RM) and substance use among South American adolescents. Cross-sectional school-based youth survey of 3,172 students (mean age, 12.8 years; 57.6% boys) in 3 large Argentinean cities. The anonymous survey queried tobacco, alcohol, and drug use using items adapted from global youth surveys. Adolescents reported M-RM restriction for internet and video game use, television programming, and movies rated for adults. Multivariate logistic regression models were used to assess the association between parental M-RM restriction and substance use after adjustment for hourly media use, measures of authoritative parenting style, sociodemographic characteristics, and sensation-seeking. Substance use rates were 10% for current smoking, 32% for current drinking alcohol, 17% for past 30-day binge drinking, and 8% for illicit drug use (marijuana or cocaine). Half of the respondents reported parental M-RM restriction (internet 52%, TV 43%, adult movies 34%, video game 25%). Parental M-RM restriction was only modestly correlated with authoritative parenting measures. In multivariate analyses M-RM restriction on all 4 venues was strongly protective for all substance use outcomes. Compared with no restriction, odds ratios for substance use for full restrictions were 0.32 (0.18-0.59), 0.53 (0.38-0.07), 0.36 (0.22-0.59), and 0.49 (0.26-0.92) for current smoking, drinking, binge drinking, and illicit drug use, respectively. The most important single M-RM venue was movies. Results of this study confirmed the protective association between parental M-RM restriction during adolescence and multiple substance use outcomes, including illicit drugs. M-RM restriction is independent of traditional parenting measures. The preponderance of the evidence supports intervention development. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  3. mRM - multiscale Routing Model for Land Surface and Hydrologic Models

    NASA Astrophysics Data System (ADS)

    Cuntz, M.; Thober, S.; Mai, J.; Samaniego, L. E.; Gochis, D. J.; Kumar, R.

    2015-12-01

    Routing streamflow through a river network is a basic step within any distributed hydrologic model. It integrates the generated runoff and allows comparison with observed discharge at the outlet of a catchment. The Muskingum routing is a textbook river routing scheme that has been implemented in Earth System Models (e.g., WRF-HYDRO), stand-alone routing schemes (e.g., RAPID), and hydrologic models (e.g., the mesoscale Hydrologic Model). Most implementations suffer from a high computational demand because the spatial routing resolution is fixed to that of the elevation model irrespective of the hydrologic modeling resolution. This is because the model parameters are scale-dependent and cannot be used at other resolutions without re-estimation. Here, we present the multiscale Routing Model (mRM) that allows for a flexible choice of the routing resolution. mRM exploits the Multiscale Parameter Regionalization (MPR) included in the open-source mesoscale Hydrologic Model (mHM, www.ufz.de/mhm) that relates model parameters to physiographic properties and allows to estimate scale-independent model parameters. mRM is currently coupled to mHM and is presented here as stand-alone Free and Open Source Software (FOSS). The mRM source code is highly modular and provides a subroutine for internal re-use in any land surface scheme. mRM is coupled in this work to the state-of-the-art land surface model Noah-MP. Simulation results using mRM are compared with those available in WRF-HYDRO for the Red River during the period 1990-2000. mRM allows to increase the routing resolution from 100m to more than 10km without deteriorating the model performance. Therefore, it speeds up model calculation by reducing the contribution of routing to total runtime from over 80% to less than 5% in the case of WRF-HYDRO. mRM thus makes discharge data available to land surface modeling with only little extra calculations.

  4. RPE and Velocity Relationships for the Back Squat, Bench Press, and Deadlift in Powerlifters.

    PubMed

    Helms, Eric R; Storey, Adam; Cross, Matt R; Brown, Scott R; Lenetsky, Seth; Ramsay, Hamish; Dillen, Carolina; Zourdos, Michael C

    2017-02-01

    Helms, ER, Storey, A, Cross, MR, Browm, SR, Lenetsky, S, Ramsay, H, Dillen, C, and Zourdos, MC. RPE and velocity relationships for the back squat, bench press, and deadlift in powerlifters. J Strength Cond Res 31(2): 292-297, 2017-The purpose of this study was to compare average concentric velocity (ACV) and rating of perceived exertion (RPE) based on repetitions in reserve on the squat, bench press, and deadlift. Fifteen powerlifters (3 women and 12 men, mean age 28.4 ± 8.5 years) worked up to a one repetition maximum (1RM) on each lift. Rating of perceived exertion was recorded on all sets, and the ACV was recorded for all sets performed at 80% of estimated 1RM and higher, up to 1RM. Rating of perceived exertion at 1RM on squat, bench press, and deadlift was 9.6 ± 0.5, 9.7 ± 0.4, and 9.6 ± 0.5, respectively and was not significantly different (p > 0.05). The ACV at 1RM on squat, bench press and deadlift was 0.23 ± 0.05, 0.10 ± 0.04, and 0.14 ± 0.05 m·second, respectively. Squat was faster than both bench press and deadlift (p > 0.001), and deadlift was faster than bench press (p = 0.05). Very strong relationships (r = 0.88-0.91) between percentage 1RM and RPE were observed on each lift. The ACV showed strong (r = -0.79 to -0.87) and very strong (r = -0.90 to 92) inverse relationships with RPE and percentage 1RM on each lift, respectively. We conclude that RPE may be a useful tool for prescribing intensity for squat, bench press, and deadlift in powerlifters, in addition to traditional methods such as percentage of 1RM. Despite high correlations between percentage 1RM and ACV, a "velocity load profile" should be developed to prescribe intensity on an individual basis with appropriate accuracy.

  5. Roller Massage: A Descriptive Survey of Allied Health Professionals.

    PubMed

    Cheatham, Scott W

    2018-04-13

    In sports medicine, the interprofessional care of athletes has become a frequent practice. This type of care often involves different interventions used among professionals. One common intervention prescribed is roller massage (RM) or self-myofascial release. The trends in the use of RM among allied health professionals is non-existent. The surveillance of such responses has not been documented. To survey and document responses in the knowledge, clinical application, and use of RM devices among allied health professionals in the United States. Cross-sectional descriptive survey study. A 20 question survey was sent to allied health professionals including physical therapists, athletic trainers, and fitness professionals. The survey covered topics such as demographics, beliefs about RM, preferred devices, exercise prescription, and client education. Results One thousand forty-two professionals (N=1042) completed the survey. Most respondents believed that RM decreases pain (82%) and increases mobility (76%). A high percentage use a foam roller in their practice (81%), recommend a full-size foam roller (49%), and believe the medium density (48%) is the most effective. A high proportion of respondents prescribe RM for injury treatment (69%) and for pre-and post-exercise (61%). They also recommend rolling daily for 30 seconds to 2 minutes per muscle group (33%) at a self-paced cadence (46%). A high percentage of respondents use patient reported outcomes (74%), joint ROM (49%), and movement-based testing (48%) to measure effects of RM. Eighty-seven percent use live instruction to educate clients and 88% believe there is a gap in the research. The results of this survey document responses in the use of RM among allied health professionals. The reported responses provide insight into how professionals are using RM as an intervention and the potential gaps between the research and professional practice. Future studies are needed to further validate these findings.

  6. Prevention of biofilm formation and removal of existing biofilms by extracellular DNases of Campylobacter jejuni.

    PubMed

    Brown, Helen L; Reuter, Mark; Hanman, Kate; Betts, Roy P; van Vliet, Arnoud H M

    2015-01-01

    The fastidious nature of the foodborne bacterial pathogen Campylobacter jejuni contrasts with its ability to survive in the food chain. The formation of biofilms, or the integration into existing biofilms by C. jejuni, is thought to contribute to food chain survival. As extracellular DNA (eDNA) has previously been proposed to play a role in C. jejuni biofilms, we have investigated the role of extracellular DNases (eDNases) produced by C. jejuni in biofilm formation. A search of 2791 C. jejuni genomes highlighted that almost half of C. jejuni genomes contains at least one eDNase gene, but only a minority of isolates contains two or three of these eDNase genes, such as C. jejuni strain RM1221 which contains the cje0256, cje0566 and cje1441 eDNase genes. Strain RM1221 did not form biofilms, whereas the eDNase-negative strains NCTC 11168 and 81116 did. Incubation of pre-formed biofilms of NCTC 11168 with live C. jejuni RM1221 or with spent medium from a RM1221 culture resulted in removal of the biofilm. Inactivation of the cje1441 eDNase gene in strain RM1221 restored biofilm formation, and made the mutant unable to degrade biofilms of strain NCTC 11168. Finally, C. jejuni strain RM1221 was able to degrade genomic DNA from C. jejuni NCTC 11168, 81116 and RM1221, whereas strain NCTC 11168 and the RM1221 cje1441 mutant were unable to do so. This was mirrored by an absence of eDNA in overnight cultures of C. jejuni RM1221. This suggests that the activity of eDNases in C. jejuni affects biofilm formation and is not conducive to a biofilm lifestyle. These eDNases do however have a potential role in controlling biofilm formation by C. jejuni strains in food chain relevant environments.

  7. Insertion of reticuloendotheliosis virus long terminal repeat into CVI988 strain of Marek’s disease virus results in enhanced growth and protection

    USDA-ARS?s Scientific Manuscript database

    It has been reported that co-cultivation of a JM/102W strain, a virulent strain of Marek’s disease virus (MDV), with reticuloendotheliosis virus (REV) resulted in the integration of REV long terminal repeat (LTR) into the MDV repeat region. The resulting virus, RM1, was unable to transform T-cells ...

  8. Preparation of Reference Material 8504, Transformer Oil

    PubMed Central

    Poster, Dianne L.; Schantz, Michele M.; Wise, Stephen A.

    2005-01-01

    A new reference material (RM), RM 8504, has been prepared for use as a diluent oil with Aroclors in transformer oil Standard Reference Materials (SRMs) 3075 to 3080 and SRM 3090 when developing and validating methods for the determination of polychlorinated biphenyls (PCBs) as Aroclors in transformer oil or similar matrices. SRMs 3075-3080 and SRM 3090 consist of individual Aroclors in the same transformer oil that was used to prepare RM 8504. A unit of RM 8504 consists of one bottle containing approximately 100 mL of transformer oil. No additional constituents have been added to the oil. PMID:27308183

  9. PET Using a GRPR Antagonist 68Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients.

    PubMed

    Zhang, Jingjing; Niu, Gang; Fan, Xinrong; Lang, Lixin; Hou, Guozhu; Chen, Libo; Wu, Huanwen; Zhu, Zhaohui; Li, Fang; Chen, Xiaoyuan

    2018-06-01

    This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, 68 Ga-RM26; to assess its clinical diagnostic value in prostate cancer patients; and to perform a direct comparison between GRPR antagonist 68 Ga-RM26 and agonist 68 Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of 68 Ga-RM26 and calculate dosimetry. A total of 28 patients with prostate cancer (17 newly diagnosed and 11 posttherapy) were recruited and provided written informed consent. All the cancer patients underwent PET/CT at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68 Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwent 68 Ga-BBN PET/CT for comparison within 1 wk. 99m Tc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of 68 Ga-M26 was well tolerated by all subjects, with no adverse symptoms being noticed or reported during the procedure and at 2-wk follow-up. The total effective dose equivalent and effective dose were 0.0912 ± 0.0140 and 0.0657 ± 0.0124 mSv/MBq, respectively. In the 17 patients with newly diagnosed prostate cancer, 68 Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUV max of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, 68 Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUV max of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUV max of 3.90 ± 3.07. Compared with 68 Ga-RM26 PET/CT, GRPR agonist 68 Ga-BBN PET/CT detected fewer primary lesions and lymph node metastases as well as demonstrated lower tracer accumulation. There was a significant positive correlation between SUV derived from 68 Ga-RM26 PET and the expression level of GRPR ( P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist 68 Ga-RM26. 68 Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. 68 Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Nonuniform continuum model for solvatochromism based on frozen-density embedding theory.

    PubMed

    Shedge, Sapana Vitthal; Wesolowski, Tomasz A

    2014-10-20

    Frozen-density embedding theory (FDET) provides the formal framework for multilevel numerical simulations, such that a selected subsystem is described at the quantum mechanical level, whereas its environment is described by means of the electron density (frozen density; ${\\rho _{\\rm{B}} (\\vec r)}$). The frozen density ${\\rho _{\\rm{B}} (\\vec r)}$ is usually obtained from some lower-level quantum mechanical methods applied to the environment, but FDET is not limited to such choices for ${\\rho _{\\rm{B}} (\\vec r)}$. The present work concerns the application of FDET, in which ${\\rho _{\\rm{B}} (\\vec r)}$ is the statistically averaged electron density of the solvent ${\\left\\langle {\\rho _{\\rm{B}} (\\vec r)} \\right\\rangle }$. The specific solute-solvent interactions are represented in a statistical manner in ${\\left\\langle {\\rho _{\\rm{B}} (\\vec r)} \\right\\rangle }$. A full self-consistent treatment of solvated chromophore, thus involves a single geometry of the chromophore in a given state and the corresponding ${\\left\\langle {\\rho _{\\rm{B}} (\\vec r)} \\right\\rangle }$. We show that the coupling between the two descriptors might be made in an approximate manner that is applicable for both absorption and emission. The proposed protocol leads to accurate (error in the range of 0.05 eV) descriptions of the solvatochromic shifts in both absorption and emission. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. High Contrast PET Imaging of GRPR Expression in Prostate Cancer Using Cobalt-Labeled Bombesin Antagonist RM26

    PubMed Central

    Thisgaard, Helge; Rosenström, Ulrika; Dam, Johan Hygum; Larhed, Mats

    2017-01-01

    High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a 55Co-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with 57Co and 55Co, stability, binding specificity, and in vitro and in vivo characteristics of 57Co-NOTA-PEG2-RM26 were studied. NOTA-PEG2-RM26 was successfully radiolabeled with 57Co and 55Co with high yields and demonstrated high stability. The radiopeptide showed retained binding specificity to GRPR in vitro and in vivo. 57Co-NOTA-PEG2-RM26 biodistribution in mice was characterized by rapid clearance of radioactivity from blood and normal non-GRPR-expressing organs and low hepatic uptake. The clearance was predominantly renal with a low degree of radioactivity reabsorption. Tumor-to-blood ratios were approximately 200 (3 h pi) and 1000 (24 h pi). The favorable biodistribution of cobalt-labeled NOTA-PEG2-RM26 translated into high contrast preclinical PET/CT (using 55Co) and SPECT/CT (using 57Co) images of PC-3 xenografts. The initial biological results suggest that 55Co-NOTA-PEG2-RM26 is a promising tracer for PET visualization of GRPR-expressing tumors. PMID:29097932

  12. A comparison of muscle activation between a Smith machine and free weight bench press.

    PubMed

    Schick, Evan E; Coburn, Jared W; Brown, Lee E; Judelson, Daniel A; Khamoui, Andy V; Tran, Tai T; Uribe, Brandon P

    2010-03-01

    The bench press exercise exists in multiple forms including the machine and free weight bench press. It is not clear though how each mode differs in its effect on muscle activation. The purpose of this study was to compare muscle activation of the anterior deltoid, medial deltoid, and pectoralis major during a Smith machine and free weight bench press at lower (70% 1 repetition maximum [1RM]) and higher (90% 1RM) intensities. Normalized electromyography amplitude values were used during the concentric phase of the bench press to compare muscle activity between a free weight and Smith machine bench press. Participants were classified as either experienced or inexperienced bench pressers. Two testing sessions were used, each of which entailed either all free weight or all Smith machine testing. In each testing session, each participant's 1RM was established followed by 2 repetitions at 70% of 1RM and 2 repetitions at 90% of 1RM. Results indicated greater activation of the medial deltoid on the free weight bench press than on the Smith machine bench press. Also, there was greater muscle activation at the 90% 1RM load than at the 70% 1RM load. The results of this study suggest that strength coaches should consider choosing the free weight bench press over the Smith machine bench press because of its potential for greater upper-body muscular development.

  13. Regional climate engineering by radiation management: Prerequisites and prospects

    NASA Astrophysics Data System (ADS)

    Quaas, Johannes; Quaas, Martin F.; Boucher, Olivier; Rickels, Wilfried

    2016-12-01

    Radiation management (RM), as an option to engineer the climate, is highly controversial and suffers from a number of ethical and regulatory concerns, usually studied in the context of the objective to mitigate the global mean temperature. In this article, we discuss the idea that RM can be differentiated and scaled in several dimensions with potential objectives being to influence a certain climate parameter in a specific region. Some short-lived climate forcers (e.g., tropospheric aerosols) exhibit strong geographical and temporal variability, potentially leading to limited-area climate responses. Marine cloud brightening and thinning or dissolution of cirrus clouds could be operated at a rather local scale. It is therefore conceivable that such schemes could be applied with the objective to influence the climate at a regional scale. From a governance perspective, it is desirable to avoid any substantial climate effects of regional RM outside the target region. This, however, could prove impossible for a sustained, long-term RM. In turn, regional RM during limited time periods could prove more feasible without effects beyond the target area. It may be attractive as it potentially provides the opportunity to target the suppression of some extreme events such as heat waves. Research is needed on the traceability of regional RM, for example, using detection and attribution methods. Incentives and implications of regional RM need to be examined, and new governance options have to be conceived.

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

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.

    The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted inmore » a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.« less

  15. 78 FR 17394 - Filing via the Internet; Electronic Tariff Filings; Revisions to Electric Quarterly Report Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. RM07-16-000; RM01-5-000; RM12-3-000] Filing via the Internet; Electronic Tariff Filings; Revisions to Electric Quarterly Report Filing Process; Notice of Technical Conference Take notice that on April 16, 2013, the staff of the...

  16. Angiotensin-Converting Enzyme Genotype and Arterial Oxygen Saturation at High Altitude in Peruvian Quechua

    PubMed Central

    Bigham, Abigail W.; Kiyamu, Melisa; León-Velarde, Fabiola; Parra, Esteban J.; Rivera-Ch, Maria; Shriver, Mark D.

    2008-01-01

    Abstract Bigham, Abigail W., Melisa Kiyamu, Fabiola León-Verlarde, Esteban J. Parra, Maria Rivera-Ch, Mark D. Shriver, and Tom D. Brutsaert. Angiotensin-converting enzyme genotype and arterial oxygen saturation at high altitude in Peruvian Quechua. High Alt. Med. Biol. 9:167–178, 2008.—The I-allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with performance benefits at high altitude (HA). In n = 142 young males and females of largely Quechua origins in Peru, we evaluated 3 specific hypotheses with regard to the HA benefits of the I-allele: (1) the I-allele is associated with higher arterial oxygen saturation (\\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document}) at HA, (2) the I-allele effect depends on the acclimatization state of the subjects, and (3) the putative I-allele effect on \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} is mediated by the isocapnic hypoxic ventilatory response (HVR, \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$$1 / {\\rm min}^{- 1} / \\%{\\rm Sa}_{\\rm O_2}{- 1}$$\\end{document}). The subject participants comprised two different study groups including BLA subjects (born at low altitude) who were lifelong sea-level residents transiently exposed to hypobaric hypoxia (<24 h) and BHA subjects (born at HA) who were lifelong residents of HA. To control for the possibility of population stratification, Native American ancestry proportion (NAAP) was estimated as a covariate for each individual using a panel of 70 ancestry-informative molecular markers (AIMS). At HA, resting and exercise \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} was strongly associated with the ACE genotype, p = 0.008 with ∼4% of the total variance in \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} attributed to ACE genotype. Moreover, I/I individuals maintained ∼2.3 percentage point higher \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} compared to I/D and D/D. This I-allele effect was evident in both BLA and BHA groups, suggesting that acclimatization state has little influence on the phenotypic expression of the ACE gene. Finally, ACE genotype was not associated with the isocapnic HVR, although HVR had a strong independent effect on \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} (p = 0.001). This suggests that the I-allele effect on \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland,xspace}\\usepackage{amsmath,amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${\\rm Sa}_{\\rm O_2}$$\\end{document} is not mediated by the peripheral control of breathing, but rather by some other central cardiopulmonary effect of the ACE gene on the renin–angiotensin–aldosterone system (RAAS). PMID:18578648

  17. Development of an Italian RM Y-STR haplotype database: Results of the 2013 GEFI collaborative exercise.

    PubMed

    Robino, C; Ralf, A; Pasino, S; De Marchi, M R; Ballantyne, K N; Barbaro, A; Bini, C; Carnevali, E; Casarino, L; Di Gaetano, C; Fabbri, M; Ferri, G; Giardina, E; Gonzalez, A; Matullo, G; Nutini, A L; Onofri, V; Piccinini, A; Piglionica, M; Ponzano, E; Previderè, C; Resta, N; Scarnicci, F; Seidita, G; Sorçaburu-Cigliero, S; Turrina, S; Verzeletti, A; Kayser, M

    2015-03-01

    Recently introduced rapidly mutating Y-chromosomal short tandem repeat (RM Y-STR) loci, displaying a multiple-fold higher mutation rate relative to any other Y-STRs, including those conventionally used in forensic casework, have been demonstrated to improve the resolution of male lineage differentiation and to allow male relative separation usually impossible with standard Y-STRs. However, large and geographically-detailed frequency haplotype databases are required to estimate the statistical weight of RM Y-STR haplotype matches if observed in forensic casework. With this in mind, the Italian Working Group (GEFI) of the International Society for Forensic Genetics launched a collaborative exercise aimed at generating an Italian quality controlled forensic RM Y-STR haplotype database. Overall 1509 male individuals from 13 regional populations covering northern, central and southern areas of the Italian peninsula plus Sicily were collected, including both "rural" and "urban" samples classified according to population density in the sampling area. A subset of individuals was additionally genotyped for Y-STR loci included in the Yfiler and PowerPlex Y23 (PPY23) systems (75% and 62%, respectively), allowing the comparison of RM and conventional Y-STRs. Considering the whole set of 13 RM Y-STRs, 1501 unique haplotypes were observed among the 1509 sampled Italian men with a haplotype diversity of 0.999996, largely superior to Yfiler and PPY23 with 0.999914 and 0.999950, respectively. AMOVA indicated that 99.996% of the haplotype variation was within populations, confirming that genetic-geographic structure is almost undetected by RM Y-STRs. Haplotype sharing among regional Italian populations was not observed at all with the complete set of 13 RM Y-STRs. Haplotype sharing within Italian populations was very rare (0.27% non-unique haplotypes), and lower in urban (0.22%) than rural (0.29%) areas. Additionally, 422 father-son pairs were investigated, and 20.1% of them could be discriminated by the whole set of 13 RM Y-STRs, which was very close to the theoretically expected estimate of 19.5% given the mutation rates of the markers used. Results obtained from a high-coverage Italian haplotype dataset confirm on the regional scale the exceptional ability of RM Y-STRs to resolve male lineages previously observed globally, and attest the unsurpassed value of RM Y-STRs for male-relative differentiation purposes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Catalysis by Methylamine Dehydrogenase and Electron Transfer to Amicyanin and Cytochrome C(551I) from Paracoccus Denitrificans.

    NASA Astrophysics Data System (ADS)

    Brooks, Harold Burns

    1995-01-01

    The quinoprotein methylamine dehydrogenase (MADH), a type I copper protein, amicyanin, and cytochrome c _{55li} form a physiologic ternary complex (Chen et al. (1994) Science 264, 86-90) in which electrons are transferred from tryptophan tryptophylquinone to copper to heme. The reduction of MADH by rm H_3- and rm D_3 -methylamine, the reoxidation of MADH by amicyanin, and the reduction of cytochrome c_{55li } by reduced amicyanin in the presence of MADH have been studied by stopped-flow spectroscopy. When rm CD_3NH_2 was used as a substrate for MADH a deuterium kinetic isotope effect of 17.2 was measured for the hydrogen abstraction step. The maximum deuterium kinetic isotope effect that was measured in steady-state kinetic experiments was 3.0. The temperature dependencies of the rate constants for the reaction of methylamine with MADH were also determined. An iminosemiquinone intermediate for the oxidation of substrate-reduced MADH by amicyanin was detected using stopped-flow spectroscopy, and the presence of the substrate derived nitrogen was confirmed by electron spin echo envelope modulation (ESEEM) spectroscopy. Marcus theory, which was used to analyze the electron transfer reaction between the dithionite-generated redox forms of MADH and amicyanin, gave values of 218 kJ rm mol^{ -1} (2.3 eV) for the reorganizational energy (lambda ) and 11.6 rm cm^{-1} for the coupling rm (H_{AB}). In contrast, the oxidation of substrate-reduced MADH by amicyanin was a gated electron transfer reaction with values for DeltaH* of 76 kJ rm mol^ {-1} and DeltaS* of -41 J rm mol^{ -1} ^circ K^ {-1}. These studies are consistent with the formation of transient unstable intermediates preceeding electron transfer between MADH and amicyanin. Preliminary investigations of the ternary complex of MADH, amicyanin, and cytochrome c_{55li } suggest two distinct cytochrome c _{55li} binding sites on amicyanin. This conclusion is supported by the biphasic nature of the stopped -flow trace, the inhibition of the rm k^ {fast}_{obs} by MADH, and the ionic strength dependence of the two phases. The slow phase had a rate of 3.1 rm s^ {-1} which is consistent with electron transfer between amicyanin and cytochrome c_ {55li} within the ternary complex. The fast phase does not exhibit saturation behavior, must have an electron transfer rate greater than 1000 rm s^{-1}, and likely involves a complex of amicyanin and cytochrome c_{55li } near the hydrophobic patch of amicyanin.

  19. Performance comparison of two resolution modeling PET reconstruction algorithms in terms of physical figures of merit used in quantitative imaging.

    PubMed

    Matheoud, R; Ferrando, O; Valzano, S; Lizio, D; Sacchetti, G; Ciarmiello, A; Foppiano, F; Brambilla, M

    2015-07-01

    Resolution modeling (RM) of PET systems has been introduced in iterative reconstruction algorithms for oncologic PET. The RM recovers the loss of resolution and reduces the associated partial volume effect. While these methods improved the observer performance, particularly in the detection of small and faint lesions, their impact on quantification accuracy still requires thorough investigation. The aim of this study was to characterize the performances of the RM algorithms under controlled conditions simulating a typical (18)F-FDG oncologic study, using an anthropomorphic phantom and selected physical figures of merit, used for image quantification. Measurements were performed on Biograph HiREZ (B_HiREZ) and Discovery 710 (D_710) PET/CT scanners and reconstructions were performed using the standard iterative reconstructions and the RM algorithms associated to each scanner: TrueX and SharpIR, respectively. RM determined a significant improvement in contrast recovery for small targets (≤17 mm diameter) only for the D_710 scanner. The maximum standardized uptake value (SUVmax) increased when RM was applied using both scanners. The SUVmax of small targets was on average lower with the B_HiREZ than with the D_710. Sharp IR improved the accuracy of SUVmax determination, whilst TrueX showed an overestimation of SUVmax for sphere dimensions greater than 22 mm. The goodness of fit of adaptive threshold algorithms worsened significantly when RM algorithms were employed for both scanners. Differences in general quantitative performance were observed for the PET scanners analyzed. Segmentation of PET images using adaptive threshold algorithms should not be undertaken in conjunction with RM reconstructions. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  20. Rationale and design of the MONITOR-ICD study: a randomized comparison of economic and clinical effects of automatic remote MONITORing versus control in patients with Implantable Cardioverter Defibrillators.

    PubMed

    Zabel, Markus; Müller-Riemenschneider, Falk; Geller, J Christoph; Brachmann, Johannes; Kühlkamp, Volker; Dissmann, Rüdiger; Reinhold, Thomas; Roll, Stephanie; Lüthje, Lars; Bode, Frank; Eckardt, Lars; Willich, Stefan N

    2014-10-01

    Implantable cardioverter defibrillator (ICD) remote follow-up and ICD remote monitoring (RM) are established means of ICD follow-up. The reduction of the number of in-office visits and the time to decision is proven, but the true clinical benefit is still unknown. Cost and cost-effectiveness of RM remain leading issues for its dissemination. The MONITOR-ICD study has been designed to assess costs, cost-effectiveness, and clinical benefits of RM versus standard-care follow-up in a prospective multicenter randomized controlled trial. Patients indicated for single- or dual-chamber ICD are eligible for the study and are implanted an RM-capable Biotronik ICD (Lumax VR-T or Lumax DR-T; Biotronik SE & Co KG, Berlin, Germany). Implantable cardioverter defibrillator programming and alert-based clinical responses in the RM group are highly standardized by protocol. As of December 2011, recruitment has been completed, and 416 patients have been enrolled. Subjects are followed-up for a minimum of 12months and a maximum of 24months, ending in January 2013. Disease-specific costs from a societal perspective have been defined as primary end point and will be compared between RM and standard-care groups. Secondary end points include ICD shocks (including appropriate and inappropriate shocks), cardiovascular hospitalizations and cardiovascular mortality, and additional health economic end points. The MONITOR-ICD study will be an important randomized RM study to report data on a primary economic end point in 2014. Its results on ICD shocks will add to the currently available evidence on clinical benefit of RM. Copyright © 2014 Mosby, Inc. All rights reserved.

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