Sample records for zinc deuteroporphyrin ix

  1. Pharmacokinetics of 2,4-di(alpha-methoxyethyl)deuteroporphyrin-IX (dimehin) and its complex with chitosan in mice with tumors

    NASA Astrophysics Data System (ADS)

    Ivanov, Andrei V.; Gradyushko, A. T.; Laptev, V. P.; Panferova, N. G.; Varlamov, V. P.; Klyashchitsky, B. A.; Reshetnickov, Andrei V.; Ponomarev, Gelii V.

    1996-01-01

    The kinetics of photosensitizer distribution and elimination have been studied using fluorescent methods in organs and tumors of A/Snell mice with embriocarcinoma inoculated into their thigh muscles for the porphyrin compound 2,4-di((alpha) -methoxyethyl)deuteroporphyrin-- IX (DMH, `Dimehin') and its complex with polysaccharide chitosan. DMH fluorescence differs in samples of liver and faeces which follows from the spectra comparison. DMH is metabolizable upon passing through liver into a form eliminated by the gastrointestinal tract as our pharmacokinetic data have shown. DMH has been found to be a short-term highly photodynamically efficient photosensitizer judging by combined analysis of our toxicological, pharmacokinetic and photodynamic research data. DMH-chitosan uptake and distribution studies have shown the complex's long-term persistence in blood circulation, high level accumulation in spleen and lungs, whereas there was no complex registered in tumors and other tissues following i.v. administration.

  2. Metallo-deuteroporphyrin as a biomimetic catalyst for the catalytic oxidation of lignin to aromatics.

    PubMed

    Zhu, Chenjie; Ding, Weiwei; Shen, Tao; Tang, Chenglun; Sun, Chenguo; Xu, Shichao; Chen, Yong; Wu, Jinglan; Ying, Hanjie

    2015-05-22

    A series of metallo-deuteroporphyrins derived from hemin were prepared as models of the cytochrome P450 enzyme. With the aid of the highly active Co(II) deuteroporphyrin complex, the catalytic oxidation system was applied for the oxidation of several lignin model compounds, and high yields of monomeric products were obtained under mild reaction conditions. It was found that the modified cobalt deuteroporphyrin that has no substituents at the meso sites but does have the disulfide linkage in the propionate side chains at the β sites exhibited much higher activity and stability than the synthetic tetraphenylporphyrin. The changes in the propionate side chains can divert the reactivity of cobalt deuteroporphyrins from the typical CC bond cleavage to CO bond cleavage. Furthermore, this novel oxidative system can convert enzymolysis lignin into depolymerized products including a significant portion of well-defined aromatic monomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A direct and simultaneous detection of zinc protoporphyrin IX, free protoporphyrin IX, and fluorescent heme degradation product in red blood cell hemolysates.

    PubMed

    Chen, Qiuying; Hirsch, Rhoda Elison

    2006-03-01

    Fluorescence emission of free protoporphyrin IX (PPIX, em. approximately 626 nm), zinc protoporphyrin IX (ZPP, em. approximately 594 nm) and fluorescent heme degradation product (FHDP, em. approximately 466 nm) are identified and simultaneously detected in mouse and human red cell hemolysates, when excited at 365 nm. A novel method is established for comparing relative FHDP, PPIX and ZPP levels in hemolysates without performing red cell porphyrin extractions. The ZPP fluorescence directly measured in hemolysates (F(365/594)) correlates with the ZPP fluorescence obtained from acetone/water extraction (R(2) = 0.9515, P < 0.0001). The relative total porphyrin (ZPP and PPIX) fluorescence obtained from direct hemolysate fluorescence measurements also correlates with red blood cell total porphyrins determined by ethyl acetate extraction (Piomelli extraction, R(2) = 0.88, P < 0.0001). These fluorescent species serves as biomarkers for alterations in Hb synthesis and Hb stability.

  4. Formation of zinc protoporphyrin IX in Parma-like ham without nitrate or nitrite.

    PubMed

    Wakamatsu, Jun-ichi; Uemura, Juichi; Odagiri, Hiroko; Okui, Jun; Hayashi, Nobutaka; Hioki, Shoji; Nishimura, Takanori; Hattori, Akihito

    2009-04-01

    Zinc protoporphyrin IX (ZPP) is a characteristic red pigment in meat products that are manufactured without the addition of a curing agent such as nitrate or nitrite. To examine the effects of impurities such as mineral components in sea salt on the formation of ZPP, we manufactured Parmatype dry-cured hams that were salted with refined salt or sea salt and examined the involvement of oxidation-reduction potential (ORP) in the formation of ZPP. The content of ZPP was increased drastically after 40 weeks. Microscopic observation showed strong fluorescence caused by ZPP muscle fiber after 40 weeks. Conversely, heme content varied considerably during processing. ORP increased during processing. However, there was no obvious difference between ham salted with refined salt and that salted with sea salt. Therefore, it was concluded that impurities in sea salt were not involved in the formation of ZPP.

  5. Assessment of the bacterial impact on the post-mortem formation of zinc protoporphyrin IX in pork meat.

    PubMed

    Ghadiri Khozroughi, Amin; Kroh, Lothar W; Schlüter, Oliver; Rawel, Harshadrai

    2018-08-01

    The post-mortem accumulation of the heme biosynthesis metabolite zinc protoporphyrin IX (ZnPP) in porcine muscle is associated with both a meat-inherent and a bacterial enzymatic reaction during meat storage. To estimate the bacterial impact on ZnPP formation, meat and meat-like media were investigated by HPLC-FLD (and MALDI-TOF-MS) after inoculation with a representative microorganism (P. fluorescens). Results indicate the principal ability of meat-inherent bacteria to form ZnPP in meat extracts and meat-like media, but not on the meat muscle. Thus it was concluded that the ZnPP formation in meat is due to a meat-inherent enzymatic reaction induced by porcine ferrochelatase (FECH), while the bacterial (FECH) induced reaction seems to be not significant. Copyright © 2018. Published by Elsevier Ltd.

  6. Dual-wavelength excitation to reduce background fluorescence for fluorescence spectroscopic quantitation of erythrocyte zinc protoporphyrin-IX and protoporphyrin-IX from whole blood and oral mucosa

    NASA Astrophysics Data System (ADS)

    Hennig, Georg; Vogeser, Michael; Holdt, Lesca M.; Homann, Christian; Großmann, Michael; Stepp, Herbert; Gruber, Christian; Erdogan, Ilknur; Hasmüller, Stephan; Hasbargen, Uwe; Brittenham, Gary M.

    2014-02-01

    Erythrocyte zinc protoporphyrin-IX (ZnPP) and protoporphyrin-IX (PPIX) accumulate in a variety of disorders that restrict or disrupt the biosynthesis of heme, including iron deficiency and various porphyrias. We describe a reagent-free spectroscopic method based on dual-wavelength excitation that can measure simultaneously both ZnPP and PPIX fluorescence from unwashed whole blood while virtually eliminating background fluorescence. We further aim to quantify ZnPP and PPIX non-invasively from the intact oral mucosa using dual-wavelength excitation to reduce the strong tissue background fluorescence while retaining the faint porphyrin fluorescence signal originating from erythrocytes. Fluorescence spectroscopic measurements were made on 35 diluted EDTA blood samples using a custom front-face fluorometer. The difference spectrum between fluorescence at 425 nm and 407 nm excitation effectively eliminated background autofluorescence while retaining the characteristic porphyrin peaks. These peaks were evaluated quantitatively and the results compared to a reference HPLC-kit method. A modified instrument using a single 1000 μm fiber for light delivery and detection was used to record fluorescence spectra from oral mucosa. For blood measurements, the ZnPP and PPIX fluorescence intensities from the difference spectra correlated well with the reference method (ZnPP: Spearman's rho rs = 0.943, p < 0.0001; PPIX: rs = 0.959, p < 0.0001). In difference spectra from oral mucosa, background fluorescence was reduced significantly, while porphyrin signals remained observable. The dual-wavelength excitation method evaluates quantitatively the ZnPP/heme and PPIX/heme ratios from unwashed whole blood, simplifying clinical laboratory measurements. The difference technique reduces the background fluorescence from measurements on oral mucosa, allowing for future non-invasive quantitation of erythrocyte ZnPP and PPIX.

  7. Influence of meat source, pH and production time on zinc protoporphyrin IX formation as natural colouring agent in nitrite-free dry fermented sausages.

    PubMed

    De Maere, Hannelore; Chollet, Sylvie; De Brabanter, Jos; Michiels, Chris; Paelinck, Hubert; Fraeye, Ilse

    2018-01-01

    Nitrite is commonly used in meat products due to its plural technological advantages. However, it is controversial because of its detrimental side effects on health. Within the context of nitrite reduction, zinc protoporphyrin IX (Zn(II)PPIX) formation in meat products as natural red colouring agent has been suggested. This investigation presents the evaluation of naturally occurring pigments, namely Zn(II)PPIX, protoporphyrin IX (PPIX) and heme in nitrite-free dry fermented sausages in function of time, meat source (pork, horsemeat and a combination of both meat sources) and pH condition. In function of time, Zn(II)PPIX and PPIX were formed and heme content decreased. Higher pH conditions promoted Zn(II)PPIX and PPIX formation, whereas the influence of pH on heme was less clear. The use of horsemeat also promoted Zn(II)PPIX formation. Moreover, even similar amounts were formed when it was combined with pork. Product redness, however, could not be related to Zn(II)PPIX formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Zinc protoporphyrin-IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase

    PubMed Central

    Metz, Richard; DuHadaway, James B.; Rust, Sonja; Munn, David H.; Muller, Alexander J.; Mautino, Mario; Prendergast, George C.

    2010-01-01

    The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) has emerged as an important driver of immune escape in a growing number of cancers and cancer-associated chronic infections. In this study, we define novel immunotherapeutic applications for the heme precursor compound zinc protoporphyrin IX (ZnPP) based on our discovery that it is a potent small molecule inhibitor of IDO. Inhibitory activity was determined using in vitro and in-cell enzyme assays as well as a novel in vivo pharmacodynamic system. An irreversible mechanism of inhibition was documented consistent with competition for heme binding in newly synthesized cellular protein. siRNA methodology and an IDO-deficient mouse strain were used to verify specificity as an IDO inhibitor. In a preclinical model of melanoma, ZnPP displayed antitumor properties that relied upon T cell function and IDO integrity. ZnPP also phenocopied the known antitumor properties of IDO inhibitors in preclinical models of skin and breast carcinoma. Our results suggest clinical evaluation of ZnPP as an adjuvant immunochemotherapy in chronic infections and cancers where there is emerging recognition of a pathophysiological role for IDO dysregulation. PMID:20530717

  9. A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX

    DOE PAGES

    Pinard, Melissa A.; Aggarwal, Mayank; Mahon, Brian P.; ...

    2015-09-23

    Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO 2to HCO 3 $-$, thereby playing a role in pH regulation. The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-basedmore » drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5 Å, anR cryst of 18.0% and anR free of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less

  10. Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill.

    PubMed Central

    Chung, K S; Madar, D A; Goldsmith, J C; Kingdon, H S; Roberts, H R

    1978-01-01

    Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules. Images PMID:711853

  11. Factor IX assay

    MedlinePlus

    ... factor assay; Serum factor IX; Hemophilic factor B; Plasma thromboplastin component; PTC ... BJ. Factor IX (Christmas factor, hemophilic factor B, plasma thromboplastin component, PTC) - blood. In: Chernecky CC, Berger ...

  12. Title IX Resource Guide

    ERIC Educational Resources Information Center

    Office for Civil Rights, US Department of Education, 2015

    2015-01-01

    Title IX of the Education Amendments of 1972 (Title IX) prohibits discrimination based on sex in education programs and activities in federally funded schools at all levels. If any part of a school district or college receives any Federal funds for any purpose, all of the operations of the district or college are covered by Title IX. The essence…

  13. ARES I-X Launch

    NASA Image and Video Library

    2009-10-27

    NASA Ares I-X Launch Director Ed Mango, left, laughs as NASA Ares I-X Assistant Launch Director Pete Nickolenko looks out the window of Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center prior to the launch of the Ares I-X rocket from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  14. A comparative study of zinc protoporphyrin IX-forming properties of animal by-products as sources for improving the color of meat products.

    PubMed

    Wakamatsu, Jun-ichi; Murakami, Naoko; Nishimura, Takanori

    2015-05-01

    The objective of this study was to obtain fundamental data for improving the color of meat products by using animal by-products. We investigated zinc protoporphyrin IX (ZnPP)-forming properties of various internal organs from pigs and chickens. ZnPP was formed in the liver, heart and kidney, whereas the porcine spleen and bile, which are involved in the metabolism of heme, did not have ZnPP-forming properties. The optimum pH values were different among the internal organs and the ZnPP-forming properties of porcine organs were better than those of chicken organs. The porcine liver showed the greatest ZnPP-forming properties among all of the internal organs investigated in this study. The optimum pH value for ZnPP formation in the liver was lower than that of skeletal muscle. Oxygen did not inhibit the formation of ZnPP in the liver, unlike in skeletal muscle. Animal by-products such as the liver have good ability for the formation of ZnPP and might be useful for improving the color of meat products. © 2014 Japanese Society of Animal Science.

  15. ARES I-X Launch

    NASA Image and Video Library

    2009-10-27

    NASA Ares I-X Launch Director Ed Mango, 3rd from left, along with other mission managers watches the launch of the Ares I-X rocket from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  16. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-26

    NASA Ares I-X Assistant Launch Director Pete Nickolenko, left, and NASA Ares I-X Launch Director Ed Mango monitor the launch countdown from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the planned launch of the Ares I-X rocket from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  17. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-26

    Mission managers, from left, NASA Constellation Program manager Jeff Hanley, Ares I-X Launch Director Ed Mango, Ares I-X mission manager Bob Ess, Ground Operations Manager Philip "Pepper" Phillips, review the latest data in Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the launch countdown of the Ares I-X rocket in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  18. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

    Code of Federal Regulations, 2010 CFR

    1998-10-01

    ... 45 Public Welfare 1 1998-10-01 1998-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

  19. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

    Code of Federal Regulations, 2010 CFR

    1997-10-01

    ... 45 Public Welfare 1 1997-10-01 1997-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

  20. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-26

    Mission managers, from left, NASA Ares I-X Assistant Launch Director Pete Nickolenko, Ground Operations Manager Philip "Pepper" Phillips, Ares I-X Launch Director Ed Mango, and Constellation Program manager Jeff Hanley review the latest weather radar from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the launch countdown of the Ares I-X rocket in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  1. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2002-10-01

    ... 45 Public Welfare 1 2002-10-01 2002-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

  2. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

    Code of Federal Regulations, 2010 CFR

    2000-10-01

    ... 45 Public Welfare 1 2000-10-01 2000-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ Public Welfare DEPARTMENT OF... procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1 Preamble paragraph numbers...

  3. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

    Code of Federal Regulations, 2010 CFR

    1999-10-01

    ... 45 Public Welfare 1 1999-10-01 1999-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ Public Welfare DEPARTMENT OF... procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1 Preamble paragraph numbers...

  4. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  5. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  6. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  7. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  8. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2003-10-01

    ... 45 Public Welfare 1 2003-10-01 2003-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  9. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2009-07-01

    ... 34 Education 1 2009-07-01 2009-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  10. 34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2015-07-01

    ... 34 Education 1 2015-07-01 2015-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  11. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2003-07-01

    ... 34 Education 1 2003-07-01 2003-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  12. 45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2006-10-01

    ... 45 Public Welfare 1 2006-10-01 2006-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  13. 34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2016-07-01

    ... 34 Education 1 2016-07-01 2016-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  14. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2007-07-01

    ... 34 Education 1 2007-07-01 2007-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  15. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2004-07-01

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  16. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  17. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2008-07-01

    ... 34 Education 1 2008-07-01 2008-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  18. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  19. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2009-10-01

    ... 45 Public Welfare 1 2009-10-01 2009-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  20. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2004-10-01

    ... 45 Public Welfare 1 2004-10-01 2004-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  1. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  2. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  3. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2005-10-01

    ... 45 Public Welfare 1 2005-10-01 2005-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  4. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2007-10-01

    ... 45 Public Welfare 1 2007-10-01 2007-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  5. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2006-07-01

    ... 34 Education 1 2006-07-01 2006-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  6. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2002-07-01

    ... 34 Education 1 2002-07-01 2002-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Regulations of the Offices of the Department...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  7. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  8. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2005-07-01

    ... 34 Education 1 2005-07-01 2005-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  9. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2001-10-01

    ... 45 Public Welfare 1 2001-10-01 2001-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  10. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2008-10-01

    ... 45 Public Welfare 1 2008-10-01 2008-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  11. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  12. 45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

    Code of Federal Regulations, 2010 CFR

    1996-10-01

    ... 45 Public Welfare 1 1996-10-01 1996-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ NONDISCRIMINATION ON THE BASIS OF SEX... Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1...

  13. 34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2017-07-01

    ... 34 Education 1 2017-07-01 2017-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

  14. Reconsidering the Status of Title IX.

    ERIC Educational Resources Information Center

    Hammer, Ben

    2003-01-01

    Discusses the controversy over Title IX and women's participation in college athletics. Critics say the mandate shortchanges men's teams, while proponents say that women's sports programs remain underfunded in spite of Title IX. Describes some proposed modifications to Title IX and their potential effects. (SLD)

  15. 45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2016-10-01

    ... 45 Public Welfare 1 2016-10-01 2016-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  16. 45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2017-10-01

    ... 45 Public Welfare 1 2017-10-01 2017-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  17. 45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2015-10-01

    ... 45 Public Welfare 1 2015-10-01 2015-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

  18. Genetics Home Reference: glycogen storage disease type IX

    MedlinePlus

    ... Health Conditions Glycogen storage disease type IX Glycogen storage disease type IX Printable PDF Open All Close ... to view the expand/collapse boxes. Description Glycogen storage disease type IX (also known as GSD IX) ...

  19. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-26

    NASA Ares I-X Launch Director Ed Mango monitors the launch countdown from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the planned launch of the Ares I-X rocket from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  20. ARES I-X Launch

    NASA Image and Video Library

    2009-10-27

    NASA Ares I-X mission managers watch as NASA's Ares I-X rocket launches from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  1. Title IX: Human Rights in School Sport.

    ERIC Educational Resources Information Center

    Graham, Peter J.

    This paper focuses on Title IX, a part of the Federal Education Amendments of 1972, and its effect upon human rights in school sport. The paper is divided into three sections. The first section reviews the purpose of Title IX and the historical developments which led to its establishment. It states that Title IX was enacted to eliminate sexual…

  2. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-25

    NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I.

  3. Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

    PubMed

    Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

    2013-05-10

    Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

  4. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-25

    NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  5. IBM PC/IX operating system evaluation plan

    NASA Technical Reports Server (NTRS)

    Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros

    1984-01-01

    An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.

  6. Title IX: With New Opportunities, Girls' Interest Rises

    ERIC Educational Resources Information Center

    Toporek, Bryan

    2012-01-01

    On June 23, 1972, President Richard M. Nixon signed into law Title IX of the Education Amendments of 1972, which prohibits gender discrimination in any federally financed education program or activity. Title IX is far-reaching, but the law is most often associated with school and college athletics. Title IX allows schools to prove their athletic…

  7. Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

    PubMed

    Métayer, Benoît; Martin-Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

    2013-11-21

    A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

  8. Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome*

    PubMed Central

    Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L.; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J.; Bateman, John F.; Wilson, Richard

    2013-01-01

    The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level, whereas matrilin-4 was verified as a novel collagen IX-binding protein. Furthermore, changes in TGFβ-induced protein βig-h3 and fibronectin abundance were found in the collagen IX knock-out but not associated with COMP ablation, indicating specific involvement in the abnormal collagen IX null cartilage. In addition, the more widespread expression of collagen XII in the collagen IX-deficient cartilage suggests an attempted compensatory response to the

  9. The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus.

    PubMed

    Hu, Yan-Dan; Pang, Wei; He, Cong-Cong; Lu, Hao; Liu, Wei; Wang, Zi-Yu; Liu, Yan-Qiang; Huang, Cheng-Yu; Jiang, Yu-Gang

    2017-11-01

    This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus. The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR. Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P < 0.05). Interestingly, the DNA methylation of the BDNF exon IX was significantly increased in the ZD group, compared with the ZA and PF groups, whereas the expression of the BDNF mRNA was decreased. In addition, the DNMT1 mRNA expression was significantly upregulated and DNMT3A was downregulated in the ZD group, but not in the ZA and PF groups. The learning and memory damage in offspring may be a result of the epigenetic changes of the BDNF genes in response to the zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.

  10. ALA-induced PpIX fluorescence in epileptogenic tissue

    NASA Astrophysics Data System (ADS)

    Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

  11. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-26

    NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009 shortly after NASA scrubbed the launch attempt due to weather. The flight test of Ares I-X, now scheduled for Wednesday, Oct. 28, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  12. Title IX.

    ERIC Educational Resources Information Center

    Justus, Janet; Brake, Deborah

    1995-01-01

    Perspectives on Title IX of the 1972 Education Amendments concerning gender equity in college sports, include those of a National Collegiate Athletic Association (NCAA) administrator and a women's law attorney. The first looks at the law's provisions, NCAA's role, and related challenges facing institutions. The second focuses on continuing gender…

  13. ARES I-X Launch Prep

    NASA Image and Video Library

    2009-10-25

    A launch countdown sign showing one day until launch of the NASA ARES I-X rocket is seen along the road between Cape Canaveral Air Force Base and the NASA Kennedy Space Center in Cape Canaveral, Florida on Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  14. Evaluation of factor IX deficiency by interdigitated electrode (IDE)

    NASA Astrophysics Data System (ADS)

    Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

    2017-03-01

    Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

  15. Gadolinium and 5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Human Gliomas: An Ex Vivo Quantitative Study to Correlate Protoporphyrin IX Levels and Blood-Brain Barrier Breakdown

    PubMed Central

    Valdés, Pablo A.; Moses, Ziev B.; Kim, Anthony; Belden, Clifford J.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

    2012-01-01

    In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA prior to surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier (BBB) breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration (CPpIX) positively correlates with gadolinium (Gd) concentrations (CGd), we performed ex vivo measurements of PpIX and of Gd using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) the latter as a quantitative biomarker of BBB breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence guided surgery for glioma .We found positive correlations between CPpIX and CGd (r = 0.58, p < 0.0001), and between CPpIX and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited association between BBB breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by ICP-MS have been used in human gliomas. PMID:22878664

  16. The Role of Title IX Coordinators on College and University Campuses

    PubMed Central

    Wiersma-Mosley, Jacquelyn D.; DiLoreto, James

    2018-01-01

    The purpose of this study was to better understand the role of Title IX coordinators and their policies across four-year universities and two-year community colleges in the United States (U.S.). There is little information regarding Title IX coordinators’ training, background, and policies on how they handle Title IX investigations regarding sexual violence. The data come from an online survey that included 692 Title IX coordinators across four-year (private and public) and two-year campuses and represented 42 different states in the US. The current study found that most Title IX coordinators were in part-time positions with less than three years of experience. Most of the coordinators and their investigators were trained in Title IX policies. Most coordinators provide Title IX training for their students and faculty, and most have completed a campus climate survey; however, 15% had not completed a survey. The findings suggest that the majority of campuses are continuing to increase their Title IX visibility; however, there are several recommendations for campuses to improve their policies. The current study was able to shed light on how Title IX coordinators do their jobs and the role they play in helping with the challenging issues surrounding sexual violence at institutions across the nation. PMID:29621177

  17. Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.

    PubMed

    Lefkowitz, J B; Monroe, D M; Kasper, C K; Roberts, H R

    1993-07-01

    A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.

  18. The MYStIX Infrared-Excess Source Catalog

    NASA Astrophysics Data System (ADS)

    Povich, Matthew S.; Kuhn, Michael A.; Getman, Konstantin V.; Busk, Heather A.; Feigelson, Eric D.; Broos, Patrick S.; Townsley, Leisa K.; King, Robert R.; Naylor, Tim

    2013-12-01

    The Massive Young Star-Forming Complex Study in Infrared and X-rays (MYStIX) project provides a comparative study of 20 Galactic massive star-forming complexes (d = 0.4-3.6 kpc). Probable stellar members in each target complex are identified using X-ray and/or infrared data via two pathways: (1) X-ray detections of young/massive stars with coronal activity/strong winds or (2) infrared excess (IRE) selection of young stellar objects (YSOs) with circumstellar disks and/or protostellar envelopes. We present the methodology for the second pathway using Spitzer/IRAC, 2MASS, and UKIRT imaging and photometry. Although IRE selection of YSOs is well-trodden territory, MYStIX presents unique challenges. The target complexes range from relatively nearby clouds in uncrowded fields located toward the outer Galaxy (e.g., NGC 2264, the Flame Nebula) to more distant, massive complexes situated along complicated, inner Galaxy sightlines (e.g., NGC 6357, M17). We combine IR spectral energy distribution (SED) fitting with IR color cuts and spatial clustering analysis to identify IRE sources and isolate probable YSO members in each MYStIX target field from the myriad types of contaminating sources that can resemble YSOs: extragalactic sources, evolved stars, nebular knots, and even unassociated foreground/background YSOs. Applying our methodology consistently across 18 of the target complexes, we produce the MYStIX IRE Source (MIRES) Catalog comprising 20,719 sources, including 8686 probable stellar members of the MYStIX target complexes. We also classify the SEDs of 9365 IR counterparts to MYStIX X-ray sources to assist the first pathway, the identification of X-ray-detected stellar members. The MIRES Catalog provides a foundation for follow-up studies of diverse phenomena related to massive star cluster formation, including protostellar outflows, circumstellar disks, and sequential star formation triggered by massive star feedback processes.

  19. Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

    PubMed

    Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

    2016-04-01

    Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. An update on anticancer drug development and delivery targeting carbonic anhydrase IX

    PubMed Central

    Parkkila, Seppo

    2017-01-01

    The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors. PMID:29181278

  1. Improved murine glioma detection following modified diet and photobleaching of skin PpIX fluorescence

    NASA Astrophysics Data System (ADS)

    Gibbs, Summer L.; O'Hara, Julia A.; Hoopes, P. Jack; Pogue, Brian W.

    2007-02-01

    The Aminolevulinic Acid (ALA) - Protoporphyrin IX (PpIX) system is unique in the world of photosensitizers in that the prodrug ALA is enzymatically transformed via the tissue of interest into fluorescently detectable levels of PpIX. This system can be used to monitor cellular metabolism of tumor tissue for applications such as therapy monitoring. Detecting PpIX fluorescence noninvasively has proven difficult due to the high levels of PpIX produced in the skin compared to other tissue both with and without ALA administration. In the current study, methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration have been examined. Use of a purified diet is found to decrease both skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration, while addition of a broad spectrum antibiotic to the water shows little effect. Following ALA administration, improved brain tumor detection is seen when skin PpIX fluorescence is photobleached via blue light prior to transmission spectroscopic measurements of tumor bearing and control animals. Both of these methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration are shown to have a large effect on the ability to detect tumor tissue PpIX fluorescence noninvasively in vivo.

  2. Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms

    NASA Astrophysics Data System (ADS)

    Marois, Mikael; Bravo, Jaime; Davis, Scott C.; Kanick, Stephen Chad

    2016-03-01

    Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation. Optical measurements showed a linear proportionality (r>0.99) between fluorescence intensity and PpIX concentration (0.1 to 10 μg/mL) over a range of Intralipid (1 to 2%) and whole blood (0.5 to 3%) for phantoms containing low surfactant (≤0.1%), with fluorescence intensities and scattering and absorption properties stable for 5 h after mixing. The role of surfactant in PpIX phantoms was found to be complex, as aggregation was evident in aqueous nonturbid phantoms with no surfactant (0% Tween), and avoided in phantoms containing Intralipid as the scattering source with no additional or low amounts of added surfactant (≤0.1% Tween). Conversely, phantoms containing higher surfactant content (>0.1% Tween) and whole blood showed interactions that distorted the fluorescence emissions.

  3. Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site.

    PubMed

    Hou, Zhuang; Lin, Bin; Bao, Yu; Yan, Hai-Ning; Zhang, Miao; Chang, Xiao-Wei; Zhang, Xin-Xin; Wang, Zi-Jie; Wei, Gao-Fei; Cheng, Mao-Sheng; Liu, Yang; Guo, Chun

    2017-05-26

    Dual-tail approach was employed to design novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable interactions with the corresponding halves of the active site. In comparison with sulfanilamide which is largely devoid of the hydrophilic and hydrophobic interactions with the two halves of the active site, the compounds so designed and synthesized in this study showed 1000-fold improvement in binding affinity. Most of the compounds inhibited the CA effectively with IC 50 values in the range of 7-152 nM. Compound 14e (IC 50 : 7 nM) was more effective than the reference drug acetazolamide (IC 50 : 30 nM). The results proved that the dual-tail approach to simultaneously matching the hydrophobic and hydrophilic halves of the active site by linking hydrophobic and hydrophilic fragments was useful for designing novel CA inhibitors. The effectiveness of those compounds was elucidated by both the experimental data and molecular docking simulations. This work laid a solid foundation for further development of novel CA IX inhibitors for cancer treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Concentrating Solar Power Projects - Solar Electric Generating Station IX |

    Science.gov Websites

    Station IX (SEGS IX) Country: United States Location: Harper Dry Lake, California (Mojave Desert) Owner(s : Parabolic trough Status: Operational Country: United States City: Harper Dry Lake State: California County

  5. Title IX: The Half Full, Half Empty Glass.

    ERIC Educational Resources Information Center

    National Advisory Council on Women's Educational Programs, Washington, DC.

    This publication discusses changes in the educational system resulting from Title IX of the 1972 Education Amendments which prohibits sex discrimination in federally assisted education programs and activities. The purpose of the publication is to help people understand and support Title IX. There are nine sections. The first section examines the…

  6. Title IX. Physical Educators for Equity. Module 4.

    ERIC Educational Resources Information Center

    Uhlir, Ann

    This module presents information on the provisions of Public Law 92 318 (Title IX) that affect the teaching of secondary school physical education. Title IX ensures equal educational opportunities for both sexes in any federally assisted educational program. It is designed to enable teachers to identify educational practices inconsistent with the…

  7. Rape on College Campuses: Reform through Title IX.

    ERIC Educational Resources Information Center

    Steinberg, Terry Nicole

    1991-01-01

    This article first, analyzes the growing problem of campus rape; second, evaluates some college rape reduction programs; third, uses case law to demonstrate that rape should be considered sex discrimination under Title IX; and, fourth, suggests an amendment to Title IX, defining rape as sex discrimination. Appropriate implementation measures by…

  8. Factor IX gene haplotypes in Amerindians.

    PubMed

    Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

    1997-02-01

    We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

  9. Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo.

    PubMed

    Monroe, D M; McCord, D M; Huang, M N; High, K A; Lundblad, R L; Kasper, C K; Roberts, H R

    1989-05-01

    Factor IX Hilo is a variant factor IX molecule that has no detectable coagulant activity. The defect in factor IX Hilo arises from a point mutation in the gene such that in the protein Arg180 is converted to a Gln. Activation of factor IX Hilo by factor Xla was monitored using the fluorescent active site probe p-aminobenzamidine. Normal factor IX showed complete activation in one hour as determined by measuring the increase in fluorescence when p-aminobenzamidine bound to activated factor IX. Factor IX Hilo showed no increase in fluorescence even after 24 hours, indicating that the active site was not exposed. Polyacrylamide gel electrophoresis showed that factor IX Hilo was cleaved to a light chain plus a larger peptide with a molecular weight equivalent to a heavy chain covalently linked to an activation peptide. Amino terminal amino acid sequencing of factor IX Hilo cleaved by factor Xla showed cleavage only at Arg145-Ala146, indicating that the Gln180-Val181 bond was not cleaved and that the active site was thus not exposed. The presence of factor IX Hilo in patient plasma was responsible for the patient having a very long ox brain prothrombin time characteristic of severe hemophilia Bm. Patient plasma had an ox brain prothrombin time of 100 seconds using a Thrombotest kit, significantly prolonged over the normal control value of 45 seconds. When factor IX Hilo was depleted from patient plasma using an immunoaffinity column, the ox brain prothrombin time decreased to 41 seconds. When factor IX Hilo was added back to depleted patient plasma, to normal plasma depleted of factor IX by the same affinity column, or to plasma from a CRM- hemophilia B patient, the ox brain prothrombin time was significantly prolonged. We conclude that the Arg180 to Gln mutation in factor IX Hilo results in a molecule that cannot be activated by factor Xla. Further, our data suggest that the mutation results in a molecule that interacts with components of the extrinsic pathway to give

  10. Ares I-X Flight Test Vehicle: Stack 5 Modal Test

    NASA Technical Reports Server (NTRS)

    Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Danel R.

    2010-01-01

    Ares I-X was the first flight test vehicle used in the development of NASA's Ares I crew launch vehicle. The Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Three modal tests were defined to verify the dynamic finite element model of the Ares I-X flight test vehicle. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report focuses on the first modal test that was performed on the top section of the vehicle referred to as Stack 5, which consisted of the spacecraft adapter, service module, crew module and launch abort system simulators. This report describes the test requirements, constraints, pre-test analysis, test operations and data analysis for the Ares I-X Stack 5 modal test.

  11. Ares I-X Flight Test Vehicle:Stack 1 Modal Test

    NASA Technical Reports Server (NTRS)

    Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Daniel R.

    2010-01-01

    Ares I-X was the first flight test vehicle used in the development of NASA s Ares I crew launch vehicle. The Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Three modal tests were defined to verify the dynamic finite element model of the Ares I-X flight test vehicle. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report focuses on the second modal test that was performed on the middle section of the vehicle referred to as Stack 1, which consisted of the subassembly from the 5th segment simulator through the interstage. This report describes the test requirements, constraints, pre-test analysis, test operations and data analysis for the Ares I-X Stack 1 modal test.

  12. The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

    PubMed

    Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

    2016-08-23

    Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

  13. Title IX: A Practical Guide to Achieving Sex Equity in Education.

    ERIC Educational Resources Information Center

    National Coalition for Women and Girls in Education.

    Title IX of the Education Amendments of 1972 is the principal federal law which prohibits sex discriminaton in education. This monograph sets forth the extent of Title IX's coverage by subject area, describes the obligations of covered institutions, and explains how victims of discrimination can enforce their Title IX right. While dealing with…

  14. Ares I-X Flight Test--The Future Begins Here

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Tuma, Margaret L.; Heitzman, Keith

    2007-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

  15. ARES I-X USS Fracture Analysis Loads Spectra Development

    NASA Technical Reports Server (NTRS)

    Larsen, Curtis; Mackey, Alden

    2008-01-01

    This report describes the development of a set of bounding load spectra for the ARES I-X launch vehicle. These load spectra are used in the determination of the critical initial flaw size (CIFS) of the welds in the ARES I-X upper stage simulator (USS).

  16. DeltaPhage—a novel helper phage for high-valence pIX phagemid display

    PubMed Central

    Nilssen, Nicolay R.; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å.

    2012-01-01

    Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems. PMID:22539265

  17. DeltaPhage--a novel helper phage for high-valence pIX phagemid display.

    PubMed

    Nilssen, Nicolay R; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å

    2012-09-01

    Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems.

  18. Ares I-X Flight Data Evaluation: Executive Overview

    NASA Technical Reports Server (NTRS)

    Huebner, Lawrence D.; Waits, David A.; Lewis, Donny L.; Richards, James S.; Coates, R. H., Jr.; Cruit, Wendy D.; Bolte, Elizabeth J.; Bangham, Michal E.; Askins, Bruce R.; Trausch, Ann N.

    2011-01-01

    NASA's Constellation Program (CxP) successfully launched the Ares I-X flight test vehicle on October 28, 2009. The Ares I-X flight was a developmental flight test to demonstrate that this very large, long, and slender vehicle could be controlled successfully. The flight offered a unique opportunity for early engineering data to influence the design and development of the Ares I crew launch vehicle. As the primary customer for flight data from the Ares I-X mission, the Ares Projects Office (APO) established a set of 33 flight evaluation tasks to correlate flight results with prospective design assumptions and models. The flight evaluation tasks used Ares I-X data to partially validate tools and methodologies in technical disciplines that will ultimately influence the design and development of Ares I and future launch vehicles. Included within these tasks were direct comparisons of flight data with preflight predictions and post-flight assessments utilizing models and processes being applied to design and develop Ares I. The benefits of early development flight testing were made evident by results from these flight evaluation tasks. This overview provides summary information from assessment of the Ares I-X flight test data and represents a small subset of the detailed technical results. The Ares Projects Office published a 1,600-plus-page detailed technical report that documents the full set of results. This detailed report is subject to the International Traffic in Arms Regulations (ITAR) and is available in the Ares Projects Office archives files.

  19. Ares I-X Flight Test--The Future Begins Here

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Robinson, Kimberly F.

    2008-01-01

    In less than one year, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will send humans to the Moon and beyond. Personnel from the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. Ares I-X will be a suborbital development flight test that will gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future flights; and demonstrate the first stage recovery system. NASA also will modify the launch infrastructure and ground and mission operations. The Ares I-X Flight Test Vehicle (FTV) will incorporate flight and mockup hardware similar in mass and weight to the operational vehicle. It will be powered by a four-segment Solid Rocket Booster (SRB), which is currently in Shuttle inventory, and will include a fifth spacer segment and new forward structures to make the booster approximately the same size and weight as the five-segment SRB. The Ares I-X flight profile will closely approximate the flight conditions that the Ares I will experience through Mach 4.5, up to approximately 130,000 feet (39,600 meters (m)) and through maximum dynamic pressure ('Max Q') of approximately 800 pounds per square foot (38.3 kilopascals (kPa)). Data from the Ares I-X flight will support the Ares I Critical Design Review (CDR), scheduled for 2010. Work continues on Ares I-X design and hardware fabrication. All of the individual elements are undergoing CDRs, followed by a two-part integrated vehicle CDR in March and July 2008. The various hardware elements are on schedule to begin deliveries to Kennedy Space Center (KSC) in early September 2008. Ares I-X is the first step in

  20. The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

    PubMed

    Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

    2013-07-01

    Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular PpIX

  1. Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

    PubMed

    Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

    2016-01-01

    Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

  2. Ares I-X Flight Test - The Future Begins Here

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.

    2008-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for an April 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission. Like the Apollo program, the Ares launch vehicles will rely upon extensive ground, flight, and orbital testing before sending the Orion crew exploration vehicle into space with humans on board. The first flight of Ares I, designated Ares I-X, will be a suborbital development flight test. Ares I-X gives NASA its first opportunity to gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future operational flights; and demonstrate the first stage recovery system. NASA also will begin modifying the launch infrastructure and fine-tuning ground and mission operations, as the agency makes the transition from the Space Shuttle to the Ares/Orion system.

  3. Title IX--Its Impact.

    ERIC Educational Resources Information Center

    Gerou, Nancy

    Fear, judgements, and violence have characterized discrimination throughout history. In sex discrimination, both sexes have a responsibility to fight discriminatory attitudes. Women should retain their distinctly feminine characteristics while at the same time being provided the same opportunities as men of equal ability. Title IX of the Education…

  4. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts

    NASA Astrophysics Data System (ADS)

    Fakhar-E-Alam, Muhammad; Akram, M. Waseem; Iqbal, Seemab; Alimgeer, K. S.; Atif, M.; Sultana, K.; Willander, M.; Wang, Zhiming M.

    2017-04-01

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  5. The Regulation of Title IX: Sex Discrimination in Student Affairs

    ERIC Educational Resources Information Center

    Malloy, Michele

    1976-01-01

    The aspects of student affairs covered by Title IX and its final regulation are emphasized since that area represents new vistas of sexual equality. The Regulation of Title IX is examined for accomplishments and oversights, effects and exemptions. (Author/LBH)

  6. Title IX and Pregnancy Discrimination in Higher Education: The New Frontier.

    PubMed

    Mason, Mary Ann; Younger, Jaclyn

    2014-01-01

    Pregnancy discrimination is a little known area covered by Title IX. According to the Title IX regulations, areas of prohibited discrimination include: admissions; hiring; coursework accommodations and completion; pregnancy leave policies and status protection upon return from leave; and health insurance coverage. These regulations will soon get more attention as the Obama Administration insists on Title IX dissemination and compliance in an effort to stop the leaky pipeline for women in the STEM fields. Research shows that pregnancy and childbirth are the major reasons why women drop out of research science in much greater numbers than men; this dropout is most likely to occur among graduate students and postdoctoral fellows who are in their peak childbearing years. A similar pattern of dropout can be seen in all fields, including related professional schools. Research also reveals that there are currently few established policies in higher education which adequately address pregnancy and childbirth in formal policies for students. This article will address new efforts by the United States Department of Education and the federal agencies to begin to seek compliance relating to Title IX and pregnancy discrimination in educational institutions. It will discuss the recent successful efforts of the U.S. Department of Education's Office for Civil Rights in investigating and settling pregnancy discrimination claims as well as the lessons learned in private action lawsuits under Title IX. Title IX private action suits have transformed athletics for women, and more recently Title IX has been applied in sexual harassment cases. Pregnancy discrimination is now the new frontier.

  7. Ares I-X Launch Vehicle Modal Test Overview

    NASA Technical Reports Server (NTRS)

    Buehrle, Ralph D.; Bartolotta, Paul A.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Parks, Russell A.; Lazor, Daniel R.

    2010-01-01

    The first test flight of NASA's Ares I crew launch vehicle, called Ares I-X, is scheduled for launch in 2009. Ares IX will use a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Flight test data will provide important information on ascent loads, vehicle control, separation, and first stage reentry dynamics. As part of hardware verification, a series of modal tests were designed to verify the dynamic finite element model (FEM) used in loads assessments and flight control evaluations. Based on flight control system studies, the critical modes were the first three free-free bending mode pairs. Since a test of the free-free vehicle is not practical within project constraints, modal tests for several configurations in the nominal integration flow were defined to calibrate the FEM. A traceability study by Aerospace Corporation was used to identify the critical modes for the tested configurations. Test configurations included two partial stacks and the full Ares I-X launch vehicle on the Mobile Launcher Platform. This paper provides an overview for companion papers in the Ares I-X Modal Test Session. The requirements flow down, pre-test analysis, constraints and overall test planning are described.

  8. Ares I-X Flight Test Vehicle Modal Test

    NASA Technical Reports Server (NTRS)

    Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Daniel R.

    2010-01-01

    The first test flight of NASA's Ares I crew launch vehicle, called Ares I-X, was launched on October 28, 2009. Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Flight test data will provide important information on ascent loads, vehicle control, separation, and first stage reentry dynamics. As part of hardware verification, a series of modal tests were designed to verify the dynamic finite element model (FEM) used in loads assessments and flight control evaluations. Based on flight control system studies, the critical modes were the first three free-free bending mode pairs. Since a test of the free-free vehicle was not practical within project constraints, modal tests for several configurations during vehicle stacking were defined to calibrate the FEM. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report describes the test requirements, constraints, pre-test analysis, test execution and results for the Ares I-X flight test vehicle modal test on the Mobile Launcher Platform. Initial comparisons between pre-test predictions and test data are also presented.

  9. Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

    2016-03-01

    Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

  10. Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

    PubMed

    Roberts, David W; Olson, Jonathan D; Evans, Linton T; Kolste, Kolbein K; Kanick, Stephen C; Fan, Xiaoyao; Bravo, Jaime J; Wilson, Brian C; Leblond, Frederic; Marois, Mikael; Paulsen, Keith D

    2018-06-01

    OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

  11. Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

    1998-07-01

    Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

  12. Political and Programmatic Impact of Affirmative Action Policy: The Case of Title IX.

    ERIC Educational Resources Information Center

    Bird, Patrick J.

    Title IX legislation has had a widespread impact on institutions of higher education. Similar laws and regulations preceding Title IX include Executive Order 11246, the Comprehensive Health Manpower and Nurse Training Act, and the Equal Employment Opportunity Act. The pervasive influence of Title IX is indicated in its provisions concerning…

  13. Effect of Photon Radiations in Semi-Rigid Artificial Tissue Sensitized by Protoporphyrin IX Encapsulated with Silica Nanoparticles

    NASA Astrophysics Data System (ADS)

    Makhadmeh, Ghaseb N.; Aziz, Azlan Abdul; Razak, Khairunisak Abdul; Al-Akhras, M.-Ali H.

    2018-02-01

    This study involves the synthesis of Protoporphyrin IX (PpIX) encapsulated with Silica Nanoparticles (SiNPs) as an application for Photodynamic therapy. Semi-rigid artificial tissues with optical features similar to human tissue were used as sample materials to ascertain the efficacy of PpIX encapsulated with SiNPs. The disparity in optical characteristics (transmittance, reflectance, scattering, and absorption) of tissues treated with encapsulated PpIX and naked PpIX under light exposure (Intensity at 408 nm ~1.19 mW/cm2) was explored. The optimal exposure times required for naked PpIX and SiNPs encapsulated PpIX to engulf Red Blood Cells (RBCs) in the artificial tissue were subsequently measured. Comparative analysis showed that the encapsulated PpIX has a 91.5 % higher efficacy than naked PpIX. The results prove the applicability of PpIX encapsulated with SiNP on artificial tissue and possible use on human tissue.

  14. Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

    PubMed

    Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

    2018-01-01

    The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

  15. Aminolevulinic acid-mediated protoporphyrin IX and photodynamic therapy for breast cancers (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chen, Bin

    2017-02-01

    Photodynamic therapy (PDT) involves the combination of a photosensitizer and light of a specific wavelength. Upon light activation in the presence of oxygen, photosensitizer molecules generate reactive oxygen species that cause cytotoxicity by inducing oxidative stress. Aminolevulinic acid (ALA) is a pro-drug used for the diagnosis and PDT treatment of various solid tumors based on endogenous production of heme precursor protoporphyrin IX (PpIX). Although nearly all types of human cells express heme biosynthesis enzymes and produce PpIX, tumor cells are found to have more PpIX production and accumulation than normal cells, allowing for the detection and treatment of solid tumors. The objective of my research is to explore therapeutic approaches to enhance ALA-based tumor detection and therapy. We have found that high ABCG2 transporter activity in triple negative breast cancer cells (TNBC) contributed to reduced PpIX levels in cells, causing them to be more resistant towards ALA-PDT. The administration of an ABCG2 inhibitor, Ko143, was able to reverse cell resistance to ALA-PDT by enhancing PpIX mitochondrial accumulation and sensitizing cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. Furthermore, since some tyrosine kinase inhibitors (TKI) are known to block ABCG2 transporter activity, we screened a panel of tyrosine kinase inhibitors to examine its effect on enhancing PpIX fluorescence and ALA-PDT efficacy. Several TKIs including lapatinib and gefitinib showed effectiveness in increasing ALA-PpIX fluorescence in TNBC leading to increased cell death after PDT administration. These results indicate that inhibiting ABCG2 transporter using TKIs is a promising approach for targeting TNBC with ALA-based modality.

  16. Why, What and Where To? Title IX, Educational Amendment of 1972

    ERIC Educational Resources Information Center

    Perry-Miller, Mitzi

    1977-01-01

    Discusses the ramifications of Title IX and asserts that access to variety without the limitations of tradition for women, both as students and employees, is the guts of Title IX as it is the heart of the community college movement. (JG)

  17. Molecular and electronic structure of thin films of protoporphyrin(IX)Fe(III)Cl

    NASA Astrophysics Data System (ADS)

    Snyder, Shelly R.; White, Henry S.

    1991-11-01

    Electrochemical, scanning tunneling microscopy (STM), and tunneling spectroscopy studies of the molecular and electronic properties of thin films of protoporphyrin(IX)Fe(III)Cl (abbreviated as PP(IX)Fe(III)Cl) on highly oriented pyrolytic graphite (HOPG) electrodes are reported. PP(IX)Fe(III)Cl films are prepared by two different methods: (1) adsorption, yielding an electrochemically-active film, and (2) irreversible electrooxidative polymerization, yielding an electrochemically-inactive film. STM images, in conjunction with electro-chemical results, indicate that adsorption of PP(IX)Fe(III)Cl from aqueous solutions onto freshly cleaved HOPG results in a film comprised of molecular aggregates. In contrast, films prepared by irreversible electrooxidative polymerization of PP(IX)Fe(III)Cl have a denser, highly structured morphology, including what appear to be small pinholes (approx. 50A diameter) in an otherwise continuous film.

  18. Tilting the Playing Field: Schools, Sports, Sex and Title IX.

    ERIC Educational Resources Information Center

    Gavora, Jessica

    This book suggests that Title IX of the Education Amendments is not creating more female athletes but instead eliminating some of the most prestigious men's sports programs in the name of gender equity. It shows how Title IX has affected every aspect of education, from kindergarten through graduate school, making profound changes in areas as…

  19. Carbonic Anhydrase IX Interacts with Bicarbonate Transporters in Lamellipodia and Increases Cell Migration via Its Catalytic Domain*

    PubMed Central

    Svastova, Eliska; Witarski, Wojciech; Csaderova, Lucia; Kosik, Ivan; Skvarkova, Lucia; Hulikova, Alzbeta; Zatovicova, Miriam; Barathova, Monika; Kopacek, Juraj; Pastorek, Jaromir; Pastorekova, Silvia

    2012-01-01

    Carbonic anhydrase IX (CA IX) is a hypoxia-induced cell surface enzyme expressed in solid tumors, and functionally involved in acidification of extracellular pH and destabilization of intercellular contacts. Since both extracellular acidosis and reduced cell adhesion facilitate invasion and metastasis, we investigated the role of CA IX in cell migration, which promotes the metastatic cascade. As demonstrated here, ectopically expressed CA IX increases scattering, wound healing and transwell migration of MDCK cells, while an inactive CA IX variant lacking the catalytic domain (ΔCA) fails to do so. Correspondingly, hypoxic HeLa cells exhibit diminished migration upon inactivation of the endogenous CA IX either by forced expression of the dominant-negative ΔCA variant or by treatment with CA inhibitor, implying that the catalytic activity is indispensable for the CA IX function. Interestingly, CA IX improves cell migration both in the absence and presence of hepatocyte growth factor (HGF), an established inducer of epithelial-mesenchymal transition. On the other hand, HGF up-regulates CA IX transcription and triggers CA IX protein accumulation at the leading edge of lamellipodia. In these membrane regions CA IX co-localizes with sodium bicarbonate co-transporter (NBCe1) and anion exchanger 2 (AE2) that are both components of the migration apparatus and form bicarbonate transport metabolon with CA IX. Moreover, CA IX physically interacts with AE2 and NBCe1 in situ, as shown here for the first time. Thus, our findings suggest that CA IX actively contributes to cell migration via its ability to facilitate ion transport and pH control at protruding fronts of moving cells. PMID:22170054

  20. Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

    2016-03-01

    Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

  1. Ares I-X Malfunction Turn Range Safety Analysis

    NASA Technical Reports Server (NTRS)

    Beaty, J. R.

    2011-01-01

    Ares I-X was the designation given to the flight test version of the Ares I rocket which was developed by NASA (also known as the Crew Launch Vehicle (CLV) component of the Constellation Program). The Ares I-X flight test vehicle achieved a successful flight test on October 28, 2009, from Pad LC-39B at Kennedy Space Center, Florida (KSC). As part of the flight plan approval for the test vehicle, a range safety malfunction turn analysis was performed to support the risk assessment and vehicle destruct criteria development processes. Several vehicle failure scenarios were identified which could have caused the vehicle trajectory to deviate from its normal flight path. The effects of these failures were evaluated with an Ares I-X 6 degrees-of-freedom (6-DOF) digital simulation, using the Program to Optimize Simulated Trajectories Version II (POST2) simulation tool. The Ares I-X simulation analysis provided output files containing vehicle trajectory state information. These were used by other risk assessment and vehicle debris trajectory simulation tools to determine the risk to personnel and facilities in the vicinity of the launch area at KSC, and to develop the vehicle destruct criteria used by the flight test range safety officer in the event of a flight test anomaly of the vehicle. The simulation analysis approach used for this study is described, including descriptions of the failure modes which were considered and the underlying assumptions and ground rules of the study.

  2. Methods of producing protoporphyrin IX and bacterial mutants therefor

    DOEpatents

    Zhou, Jizhong; Qiu, Dongru; He, Zhili; Xie, Ming

    2016-03-01

    The presently disclosed inventive concepts are directed in certain embodiments to a method of producing protoporphyrin IX by (1) cultivating a strain of Shewanella bacteria in a culture medium under conditions suitable for growth thereof, and (2) recovering the protoporphyrin IX from the culture medium. The strain of Shewanella bacteria comprises at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX. In certain embodiments of the method, the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or of shew_1140. In other embodiments, the presently disclosed inventive concepts are directed to mutant strains of Shewanella bacteria having at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX during cultivation of the bacteria. In certain embodiments the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or shew_1140.

  3. The History, Uses, and Abuses of Title IX. 2016 Bulletin

    ERIC Educational Resources Information Center

    American Association of University Professors, 2016

    2016-01-01

    This report, an evaluation of the history and current uses of Title IX, is the result of a joint effort by a subcommittee that included members of the AAUP's Committee A on Academic Freedom and Tenure and the Committee on Women in the Academic Profession. The report identifies tensions between current interpretations of Title IX and the academic…

  4. A License for Bias: Sex Discrimination, Schools, and Title IX.

    ERIC Educational Resources Information Center

    Morse, Susan Ed.

    This report discusses non-sports-related Title IX complaints filed with the Department of Education's Office for Civil Rights (OCR) from 1993-1997. Its purpose is to dispel the popular belief that Title IX is a sports-equity law and to determine the effectiveness of the legislation. The document examines the kinds of complaints filed, the status…

  5. ALA-induced PpIX spectroscopy for brain tumor image-guided surgery

    NASA Astrophysics Data System (ADS)

    Valdes, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Maximizing the extent of brain tumor resection correlates with improved survival and quality of life outcomes in patients. Optimal surgical resection requires accurate discrimination between normal and abnormal, cancerous tissue. We present our recent experience using quantitative optical spectroscopy in 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided resection. Exogenous administration of ALA leads to preferential accumulation in tumor tissue of the fluorescent compound, PpIX, which can be used for in vivo surgical guidance. Using the state of the art approach with a fluorescence surgical microscope, we have been able to visualize a subset of brain tumors, but the sensitivity and accuracy of fluorescence detection for tumor tissue with this system are low. To take full advantage of the biological selectivity of PpIX accumulation in brain tumors, we used a quantitative optical spectroscopy system for in vivo measurements of PpIX tissue concentrations. We have shown that, using our quantitative approach for determination of biomarker concentrations, ALA-induced PpIX fluorescence-guidance can achieve accuracies of greater than 90% for most tumor histologies. Here we show multivariate analysis of fluorescence and diffuse reflectance signals in brain tumors with comparable diagnostic performance to our previously reported quantitative approach. These results are promising, since they show that technological improvements in current fluorescence-guided surgical technologies and more biologically relevant approaches are required to take full advantage of fluorescent biomarkers, achieve better tumor identification, increase extent of resection, and subsequently, lead to improve survival and quality of life in patients.

  6. Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites.

    PubMed Central

    Diab, M; Wu, J J; Eyre, D R

    1996-01-01

    Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage. PMID:8660302

  7. Modulation of the endogenous production of protoporphyrin IX in a yeast-based model organism

    NASA Astrophysics Data System (ADS)

    Joniová, Jaroslava; Gerelli, Emmanuel; Wagnières, Georges

    2017-02-01

    The main aim of this study was to assess conditions at which simple yeast-based model organism produces maximal levels of protoporphyrin IX (PpIX) after an exogenous administration of its precursor, 5-aminolevulinic acid (ALA), and the ferrous-ion chelator 2,2'-bipyridyl. We observed that the fluorescing porphyrin, produced after these administrations, was likely to be PpIX since fluorescence spectroscopy of the porphyrins produced endogenously in yeast cells resembles that of PpIX in DMSO and in vivo in the chick's chorioallantoic membrane model. Also, fluorescence lifetimes of these porphyrins are very similar to that of PpIX in vitro and in vivo. This suggests that PpIX is the main fluorescent compound produced by yeast in our conditions. We found that the conditions at which yeast produces the maximal PpIX were a synchronous administration of 5 μM ALA and 1 mM 2,2'-bipyridyl for yeast incubated in aqueous glucose and 1 mM 2,2'-bipyridyl in the presence of YPD medium. Such a simple model is of high interest to study basic mechanisms involved in the mitochondrial respiration since PpIX, which is produced in this organelle, can be used as an oxygen sensor, or to perform photodynamic therapy and photodiagnosis. Since the absorption and scattering coefficients of this model are much smaller than those of soft tissues over the visible part of the spectrum, a version of this model loaded with appropriated amounts of light absorbing and scattering particles could be designed as a phantom to mimic tumors containing PpIX, a useful tool to optimize certain cancer photodetection set-ups.

  8. Ares I-X Vibroacoustic Environments

    NASA Technical Reports Server (NTRS)

    Larsen, Curtis E.; Schuster, David M.; Kaufman, Daniel S.

    2009-01-01

    This paper provides a summary of the NASA Engineering and Safety Center (NESC) team recommendations and observations following participation with the Ares I-X Vibroacoustic (VA) Environments Panel in meetings at the Kennedy Space Center (KSC) and the Marshall Space Flight Center (MSFC) in March and April 2008, respectively.

  9. 5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

    PubMed

    Valdes, Pablo A; Bekelis, Kimon; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E; Erkmen, Kadir; Paulsen, Keith D; Roberts, David W

    2014-03-01

    The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

  10. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

    PubMed Central

    Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

    2014-01-01

    BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

  11. Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

    PubMed

    Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

    2014-09-01

    Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  12. Protoporphyrin IX fluorescence as potential indicator of psoriasis severity and progression.

    PubMed

    Wang, Bo; Xu, Yu-Ting; Zhang, Li; Zheng, Jie; Sroka, Ronald; Wang, Hong-Wei; Wang, Xiu-Li

    2017-09-01

    In psoriatic lesions, fluorescence diagnosis with blue light can detect protoporphyrin IX accumulation, especially after topical 5-aminolaevulinic acid (ALA) application. However, variable fluorescence distributions, interpersonal variations and long incubation time limit its wide application in clinic. This study is aimed to identify a consistent and convenient method to facilitate diagnosis and evaluation of psoriatic lesions. 104 psoriatic lesions from 30 patients were evaluated. Single lesion PSI scoring and fluorescence by macrospectrofluorometry were recorded on each lesion before and after treatment with narrow-band UVB. Punctate red fluorescence, emitted mainly by protoporphyrin IX, is observed in some psoriatic lesions. According to psoriasis severity index, fluorescence-positive lesions are more severe than lesions without fluorescence. We found a significant positive correlation between psoriasis severity and fluorescence intensity from protoporphyrin IX. Protoporphyrin IX-induced red fluorescence can be used as a novel and convenient approach for psoriasis diagnosis and progression evaluation. Copyright © 2017. Published by Elsevier B.V.

  13. In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

    PubMed

    Limentani, S A; Gowell, K P; Deitcher, S R

    1995-04-01

    This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Hardware and Programmatic Progress on the Ares I-X Flight Test

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.

    2008-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will execute the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle; which, together with the Ares V cargo launch vehicle (Figure 1), will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and, in some cases, already fabricating vehicle hardware in preparation for an April 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

  15. Development and characterisation of a brain tumour mimicking protoporphyrin IX fluorescence phantom (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xie, Yijing; Tisca, Cristiana; Peveler, William; Noimark, Sacha; Desjardins, Adrien E.; Parkin, Ivan P.; Ourselin, Sebastien; Vercauteren, Tom

    2017-02-01

    5-ALA-PpIX fluorescence-guided brain tumour resection can increase the accuracy at which cancerous tissue is removed and thereby improve patient outcomes, as compared with standard white light imaging. Novel optical devices that aim to increase the specificity and sensitivity of PpIX detection are typically assessed by measurements in tissue-mimicking optical phantoms of which all optical properties are defined. Current existing optical phantoms specified for PpIX lack consistency in their optical properties, and stability with respect to photobleaching, thus yielding an unstable correspondence between PpIX concentration and the fluorescence intensity. In this study, we developed a set of aqueous-based phantoms with different compositions, using deionised water or PBS buffer as background medium, intralipid as scattering material, bovine haemoglobin as background absorber, and either PpIX dissolved in DMSO or a novel nanoparticle with similar absorption and emission spectrum to PpIX as the fluorophore. We investigated the phantom stability in terms of aggregation and photobleaching by comparing with different background medium and fluorophores, respectively. We characterised the fluorescence intensity of the fluorescent nanoparticle in different concentration of intralipid and haemoglobin and its time-dependent stability, as compared to the PpIX-induced fluorescence. We corroborated that the background medium was essential to prepare a stable aqueous phantom. The novel fluorescent nanoparticle used as surrogate fluorophore of PpIX presented an improved temporal stability and a reliable correspondence between concentration and emission intensity. We proposed an optimised phantom composition and recipe to produce reliable and repeatable phantom for validation of imaging device.

  16. Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kumar, M. Suresh; Aruna, P.; Ganesan, S.

    2018-03-01

    One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

  17. The H IX galaxy survey - II. H I kinematics of H I eXtreme galaxies

    NASA Astrophysics Data System (ADS)

    Lutz, K. A.; Kilborn, V. A.; Koribalski, B. S.; Catinella, B.; Józsa, G. I. G.; Wong, O. I.; Stevens, A. R. H.; Obreschkow, D.; Dénes, H.

    2018-05-01

    By analysing a sample of galaxies selected from the H I Parkes All Sky Survey (HIPASS) to contain more than 2.5 times their expected H I content based on their optical properties, we investigate what drives these H I eXtreme (H IX) galaxies to be so H I-rich. We model the H I kinematics with the Tilted Ring Fitting Code TiRiFiC and compare the observed H IX galaxies to a control sample of galaxies from HIPASS as well as simulated galaxies built with the semi-analytic model DARK SAGE. We find that (1) H I discs in H IX galaxies are more likely to be warped and more likely to host H I arms and tails than in the control galaxies, (2) the average H I and average stellar column density of H IX galaxies is comparable to the control sample, (3) H IX galaxies have higher H I and baryonic specific angular momenta than control galaxies, (4) most H IX galaxies live in higher spin haloes than most control galaxies. These results suggest that H IX galaxies are H I-rich because they can support more H I against gravitational instability due to their high specific angular momentum. The majority of the H IX galaxies inherits their high specific angular momentum from their halo. The H I content of H IX galaxies might be further increased by gas-rich minor mergers. This paper is based on data obtained with the Australia Telescope Compact Array through the large program C 2705.

  18. ARES I-X Launch

    NASA Image and Video Library

    2009-10-27

    NASA's Ares I-X rocket is seen through the windows of Firing Room One of teh Launch Control Center (LCC) at the Kennedy Space Center as it launches from pad 39b in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

  19. Urothelial conversion of 5-aminolevulinic acid to protoporphyrin IX following oral or intravesical administration

    NASA Astrophysics Data System (ADS)

    Moore, Ronald B.; Miller, Gerald G.; Brown, Kevin; Bhatnagar, Rakesh; Tulip, John; McPhee, Malcolm S.

    1995-03-01

    Preferential conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin-IX (Pp-IX) occurs in malignant tissue, with accumulation to diagnostic and therapeutic levels. Recent studies have suggested selective conversion in epithelial tissue following oral or intravenous administration. Topical application avoids systemic photosensitization. However, the glycosaminoglycan (GAG) layer lining the urinary bladder is believed to be a protective barrier generally limiting mucosal absorption. Our objective was to evaluate uptake and conversion of 5-ALA following intravesical or oral administration. Using a rat model, Pp-IX content within epithelial and muscularis layers was quantitated by fluorescence confocal microscopy. Following intravesical administration, Pp-IX accumulated predominantly in the urothelium; whereas following oral administration, Pp-IX accumulated in both the urothelium and muscularis. Intravesical 5-ALA administration is feasible and may afford selective photosensitization of the urothelium for treatment of carcinoma in situ.

  20. Ares I-X: First Flight of a New Generation

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Askins, Bruce R.

    2010-01-01

    The Ares I-X suborbital development flight test demonstrated NASA s ability to design, develop, launch and control a new human-rated launch vehicle (Figure 14). This hands-on missions experience will provide the agency with necessary skills and insights regardless of the future direction of space exploration. The Ares I-X team, having executed a successful launch, will now focus on analyzing the flight data and extracting lessons learned that will be used to support the development of future vehicles.

  1. Not Second-Class: Title IX, Equity, and Girls' High School Sports

    ERIC Educational Resources Information Center

    Stader, David L.; Surface, Jeanne L.

    2014-01-01

    Title IX is designed to protect students from discrimination based on sex in any educational institution that receives financial assistance. This article focuses on Title IX as it applies to high school athletic programs by considering the trial of a high school district in California. A federal court found considerable inequalities between boys…

  2. Ares I-X: First Flight of a New Era

    NASA Technical Reports Server (NTRS)

    Davis, Stephen R.; Askins, Bruce R.

    2010-01-01

    Since 2005, NASA s Constellation Program has been designing, building, and testing the next generation of launch and space vehicles to carry humans beyond low-Earth orbit (LEO). The Ares Projects at Marshall Space Flight Center (MSFC) are developing the Ares I crew launch vehicle and Ares V cargo launch vehicle. On October 28, 2009, the first development flight test of the Ares I crew launch vehicle, Ares I-X, lifted off from a launch pad at Kennedy Space Center (KSC) on successful suborbital flight. Basing exploration launch vehicle designs on Ares I-X information puts NASA one step closer to full-up "test as you fly," a best practice in vehicle design. Although the final Constellation Program architecture is under review, the Ares I-X data and experience in vehicle design and operations can be applied to any launch vehicle. This paper presents the mission background as well as results and lessons learned from the flight.

  3. Probing the Highly Efficient Electron Transfer Dynamics between Zinc Protoporphyrin IX and Sodium Titanate Nanosheets.

    PubMed

    Biswas, Sudipta; Mukherjee, Debdyuti; De, Swati; Kathiravan, Arunkumar

    2016-09-15

    Sodium titanate nanosheets (NaTiO2 NS) have been prepared by a new method and completely characterized by TEM, SEM, XRD, EDX, and XPS techniques. The sensitization of nanosheets is carried out with Zn protoporphyrin IX (ZnPPIX). The emission intensity of ZnPPIX is quenched by NaTiO2 NS, and the dominant process for this quenching has been attributed to the process of photoinduced electron injection from excited ZnPPIX to the nanosheets. Time resolved fluorescence measurement was used to elucidate the process of electron injection from the singlet state of ZnPPIX to the conduction band of NaTiO2 NS. Electron injection from the dye to the semiconductor is very fast (ket ≈ 10(11) s(-1)), much faster than previously reported rates. The large two-dimensional surface offered by the NaTiO2 NS for interaction with the dye and the favorable driving force for electron injection from ZnPPIX to NaTiO2 NS (ΔGinj = -0.66 V) are the two important factors responsible for such efficient electron injection. Thus, NaTiO2 NS can serve as an effective alternative to the use of TiO2 nanoparticles in dye sensitized solar cells (DSSCs).

  4. Ares I-X: On the Threshold of Exploration

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Askins, Bruce

    2009-01-01

    Ares I-X, the first flight of the Ares I crew launch vehicle, is less than a year from launch. Ares I-X will test the flight characteristics of Ares I from liftoff to first stage separation and recovery. The flight also will demonstrate the computer hardware and software (avionics) needed to control the vehicle; deploy the parachutes that allow the first stage booster to land in the ocean safely; measure and control how much the rocket rolls during flight; test and measure the effects of first stage separation; and develop and try out new ground handling and rocket stacking procedures in the Vehicle Assembly Building (VAB) and first stage recovery procedures at Kennedy Space Center (KSC) in Florida. All Ares I-X major elements have completed their critical design reviews, and are nearing final fabrication. The first stage--four-segment solid rocket booster from the Space Shuttle inventory--incorporates new simulated forward structures to match the Ares I five-segment booster. The upper stage, Orion crew module, and launch abort system will comprise simulator hardware that incorporates developmental flight instrumentation for essential data collection during the mission. The upper stage simulator consists of smaller cylindrical segments, which were transported to KSC in fall 2008. The crew module and launch abort system simulator were shipped in December 2008. The first stage hardware, active roll control system (RoCS), and avionics components will be delivered to KSC in 2009. This paper will provide detailed statuses of the Ares I-X hardware elements as NASA's Constellation Program prepares for this first flight of a new exploration era in the summer of 2009.

  5. Why, What and Where To? Title IX, Educational Amendment of 1972.

    ERIC Educational Resources Information Center

    Perry-Miller, Mitzi

    Three years after Title IX of the Education Amendments of 1972 became law, the U. S. Department of Health, Education, and Welfare provided regulations for the implementation of Title IX. This report reviews the implications of these regulations as well as several of the court cases in which discrimination on the basis of sex has been declared…

  6. Singlet oxygen feedback delayed fluorescence of protoporphyrin IX in organic solutions.

    PubMed

    Vinklárek, Ivo S; Scholz, Marek; Dědic, Roman; Hála, Jan

    2017-04-12

    Delayed fluorescence (DF) of protoporphyrin IX (PpIX) has been recently proposed as a tool for monitoring of mitochondrial oxygen tension in vivo as well as for observation of the effectiveness of photodynamic therapy (PDT) [E. G. Mik, Anesth. Analg., 2013, 117, 834-346; F. Piffaretti et al., J. Biomed. Opt., 2012, 17, 115007]. However, the efficiency of the mechanism of thermal activation (E-type DF), which was considered in the papers, is limited due to a large energy gap between the first excited singlet and the first triplet state of PpIX at room or body temperatures. Moreover, the energy gap is roughly equal to other porphyrinoid photosensitizers that generate DF mostly through the Singlet Oxygen Feedback-Induced mechanism (SOFDF) under certain conditions [M. Scholz and R. Dědic, Singlet Oxygen: Applications in Biosciences and Nanosciences, 2016, vol. 2, pp. 63-81]. The mechanisms of delayed fluorescence of PpIX dissolved either in dimethylformamide (DMF) or in the mixture of DMF with ethylene glycol (EG) were investigated at atmospheric partial pressure of oxygen by means of a simultaneous time-resolved detection of 1 O 2 phosphorescence and PpIX DF which makes a direct comparison of the kinetics and lifetimes of both the luminescence channels possible. Samples of PpIX (100 μM) exhibit concave DF kinetics, which is a typical footprint of the SOFDF mechanism. The dramatic decrease in the DF intensity after adding a selective 1 O 2 quencher sodium azide (NaN 3 , 10 mM) proves that >90% of DF is indeed generated through SOFDF. Moreover, the analysis of the DF kinetics in the presence of NaN 3 implies that the second significant mechanism of DF generation is the triplet-triplet annihilation (P-type DF). The bimolecular mechanism of DF was further confirmed by the decrease of the DF intensity in the more viscous mixture DMF/EG and by the increase of the ratio of DF to the prompt fluorescence (PF) intensity with the increasing excitation intensity. These results

  7. Ares I-X Flight Test Vehicle Similitude to the Ares I Crew Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Huebner, Lawrence D.; Smith, R. Marshall; Campbell, John R.; Taylor, Terry L.

    2009-01-01

    The Ares I-X Flight Test Vehicle is the first in a series of flight test vehicles that will take the Ares I Crew Launch Vehicle design from development to operational capability. Ares I-X is scheduled for a 2009 flight date, early enough in the Ares I design and development process so that data obtained from the flight can impact the design of Ares I before its Critical Design Review. Decisions on Ares I-X scope, flight test objectives, and FTV fidelity were made prior to the Ares I systems requirements being baselined. This was necessary in order to achieve a development flight test to impact the Ares I design. Differences between the Ares I-X and the Ares I configurations are artifacts of formulating this experimental project at an early stage and the natural maturation of the Ares I design process. This paper describes the similarities and differences between the Ares I-X Flight Test Vehicle and the Ares I Crew Launch Vehicle. Areas of comparison include the outer mold line geometry, aerosciences, trajectory, structural modes, flight control architecture, separation sequence, and relevant element differences. Most of the outer mold line differences present between Ares I and Ares I-X are minor and will not have a significant effect on overall vehicle performance. The most significant impacts are related to the geometric differences in Orion Crew Exploration Vehicle at the forward end of the stack. These physical differences will cause differences in the flow physics in these areas. Even with these differences, the Ares I-X flight test is poised to meet all five primary objectives and six secondary objectives. Knowledge of what the Ares I-X flight test will provide in similitude to Ares I - as well as what the test will not provide - is important in the continued execution of the Ares I-X mission leading to its flight and the continued design and development of Ares I.

  8. The Development of the Ares I-X Flight Test

    NASA Technical Reports Server (NTRS)

    Ess, Robert H.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) Constellation Program (CxP) has identified a series of tests to provide insight into the design and development of the Ares I Crew Launch Vehicle (CLV) and the Orion Crew Exploration Vehicle (CEV). Ares I-X was created as the first suborbital development flight test to help meet CxP objectives. The Ares I-X flight vehicle is an early operational model of Ares, with specific emphasis on Ares I and ground operation characteristics necessary to meet Ares I-X flight test objectives. Ares I-X will encompass the design and construction of an entire system that includes the Flight Test Vehicle (FTV) and associated operations. The FTV will be a test model based on the Ares I design. Select design features will be incorporated in the FTV design to emulate the operation of the CLV in order to meet the flight test objectives. The operations infrastructure and processes will be customized for Ares I-X, while still providing data to inform the developers of the launch processing system for Ares/Orion. The FTV is comprised of multiple elements and components that will be developed at different locations. The components will be delivered to the launch/assembly site, Kennedy Space Center (KSC), for assembly of the elements and components into an integrated, flight-ready, launch vehicle. The FTV will fly a prescribed trajectory in order to obtain the necessary data to meet the objectives. Ares I-X will not be commanded or controlled from the ground during flight, but the FTV will be equipped with telemetry systems, a data recording capability and a flight termination system (FTS). The in-flight part of the test includes a trajectory to simulate maximum dynamic pressure during flight and perform a stage separation representative of the CLV. The in-flight test also includes separation of the Upper Stage Simulator (USS) from the First Stage and recovery of the First Stage. The data retrieved from the flight test will be analyzed

  9. Ares I-X Flight Test Vehicle Similitude to the Ares I Crew Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Huebner, Lawrence D.; Smith, R. Marshall; Campbell, John R., Jr.; Taylor, Terry L.

    2008-01-01

    The Ares I-X Flight Test Vehicle is the first in a series of flight test vehicles that will take the Ares I Crew Launch Vehicle design from development to operational capability. The test flight is scheduled for April 2009, relatively early in the Ares I design process so that data obtained from the flight can impact the design of Ares I before its Critical Design Review. Because of the short time frame (relative to new launch vehicle development) before the Ares I-X flight, decisions about the flight test vehicle design had to be made in order to complete analysis and testing in time to manufacture the Ares I-X vehicle hardware elements. This paper describes the similarities and differences between the Ares I-X Flight Test Vehicle and the Ares I Crew Launch Vehicle. Areas of comparison include the outer mold line geometry, aerosciences, trajectory, structural modes, flight control architecture, separation sequence, and relevant element differences. Most of the outer mold line differences present between Ares I and Ares I-X are minor and will not have a significant effect on overall vehicle performance. The most significant impacts are related to the geometric differences in Orion Crew Exploration Vehicle at the forward end of the stack. These physical differences will cause differences in the flow physics in these areas. Even with these differences, the Ares I-X flight test is poised to meet all five primary objectives and six secondary objectives. Knowledge of what the Ares I-X flight test will provide in similitude to Ares I as well as what the test will not provide is important in the continued execution of the Ares I-X mission leading to its flight and the continued design and development of Ares I.

  10. Subsurface PpIX imaging in vivo with ultrasound-guided tomographic spectroscopy: reconstruction vs. born-normalized data

    NASA Astrophysics Data System (ADS)

    Flynn, Brendan P.; D'Souza, Alisha V.; Kanick, Stephen C.; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

    2013-03-01

    Aminolevulinic acid (ALA)-induced Protoporphyrin IX (PpIX)-based photodynamic therapy (PDT) is an effective treatment for skin cancers including basal cell carcinoma (BCC). Topically applied ALA promotes PpIX production preferentially in tumors, and many strategies have been developed to increase PpIX distribution and PDT treatment efficacy at depths > 1mm is not fully understood. While surface imaging techniques provide useful diagnosis, dosimetry, and efficacy information for superficial tumors, these methods cannot interrogate deeper tumors to provide in situ insight into spatial PpIX distributions. We have developed an ultrasound-guided, white-light-informed, tomographics spectroscopy system for the spatial measurement of subsurface PpIX. Detailed imaging system specifications, methodology, and optical-phantom-based characterization will be presented separately. Here we evaluate preliminary in vivo results using both full tomographic reconstruction and by plotting individual tomographic source-detector pair data against US images.

  11. Ares I-X Flight Test - On the Fast Track to the Future

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Robinson, Kimberly F.

    2008-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will send humans to the Moon and beyond. Personnel from the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for an April 2009 launch. Ares I-X will be a suborbital development flight test that will gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future flights; and demonstrate the first stage recovery system. NASA also will modify the launch infrastructure and ground and mission operations. The Ares I-X Flight Test Vehicle (FTV) will incorporate flight and mockup hardware similar in mass and weight to the operational vehicle. It will be powered by a four-segment Solid Rocket Booster (SRB), which is currently in Shuttle inventory, and will include a fifth spacer segment and new forward structures to make the booster approximately the same size and weight as the five-segment SRB. The Ares I-X flight profile will closely approximate the flight conditions that the Ares I will experience through Mach 4.5, up to approximately130,OOO feet and through maximum dynamic pressure ("Max Q") of approximately 800 pounds per square foot. Data from the Ares I-X flight will support the Ares I Critical Design Review (CDR), scheduled for 2010. Work continues on Ares I-X design and hardware fabrication. All of the individual elements are undergoing CDRs, followed by an integrated vehicle CDR in March 2008. The various hardware elements are on schedule to begin deliveries to Kennedy Space Center (KSC) in early September 2008.

  12. A Place on the Team: The Triumph and Tragedy of Title IX

    ERIC Educational Resources Information Center

    Suggs, Welch

    2006-01-01

    "A Place on the Team" is the inside story of how Title IX revolutionized American sports. The federal law guaranteeing women's rights in education, Title IX opened gymnasiums and playing fields to millions of young women previously locked out. Journalist Welch Suggs chronicles both the law's successes and failures-the exciting…

  13. Time Domain Tool Validation Using ARES I-X Flight Data

    NASA Technical Reports Server (NTRS)

    Hough, Steven; Compton, James; Hannan, Mike; Brandon, Jay

    2011-01-01

    The ARES I-X vehicle was launched from NASA's Kennedy Space Center (KSC) on October 28, 2009 at approximately 11:30 EDT. ARES I-X was the first test flight for NASA s ARES I launch vehicle, and it was the first non-Shuttle launch vehicle designed and flown by NASA since Saturn. The ARES I-X had a 4-segment solid rocket booster (SRB) first stage and a dummy upper stage (US) to emulate the properties of the ARES I US. During ARES I-X pre-flight modeling and analysis, six (6) independent time domain simulation tools were developed and cross validated. Each tool represents an independent implementation of a common set of models and parameters in a different simulation framework and architecture. Post flight data and reconstructed models provide the means to validate a subset of the simulations against actual flight data and to assess the accuracy of pre-flight dispersion analysis. Post flight data consists of telemetered Operational Flight Instrumentation (OFI) data primarily focused on flight computer outputs and sensor measurements as well as Best Estimated Trajectory (BET) data that estimates vehicle state information from all available measurement sources. While pre-flight models were found to provide a reasonable prediction of the vehicle flight, reconstructed models were generated to better represent and simulate the ARES I-X flight. Post flight reconstructed models include: SRB propulsion model, thrust vector bias models, mass properties, base aerodynamics, and Meteorological Estimated Trajectory (wind and atmospheric data). The result of the effort is a set of independently developed, high fidelity, time-domain simulation tools that have been cross validated and validated against flight data. This paper presents the process and results of high fidelity aerospace modeling, simulation, analysis and tool validation in the time domain.

  14. Ares I-X Flight Test Development Challenges and Success Factors

    NASA Technical Reports Server (NTRS)

    Askins, Bruce; Davis, Steve; Olsen, Ronald; Taylor, James

    2010-01-01

    The NASA Constellation Program's Ares I-X rocket launched successfully on October 28, 2009 collecting valuable data and providing risk reduction for the Ares I project. The Ares I-X mission was formulated and implemented in less than four years commencing with the Exploration Systems Architecture Study in 2005. The test configuration was founded upon assets and processes from other rocket programs including Space Shuttle, Atlas, and Peacekeeper. For example, the test vehicle's propulsion element was a Shuttle Solid Rocket Motor. The Ares I-X rocket comprised a motor assembly, mass and outer mold line simulators of the Ares I Upper Stage, Orion Spacecraft and Launch Abort System, a roll control system, avionics, and other miscellaneous components. The vehicle was 327 feet tall and weighed approximately 1,800,000 pounds. During flight the rocket reached a maximum speed of Mach 4.8 and an altitude of 150,000 feet. The vehicle demonstrated staging at 130,000 feet, tested parachutes for recovery of the motor, and utilized approximately 900 sensors for data collection. Developing a new launch system and preparing for a safe flight presented many challenges. Specific challenges included designing a system to withstand the environments, manufacturing large structures, and re-qualifying heritage hardware. These and other challenges, if not mitigated, may have resulted in test cancellation. Ares I-X succeeded because the mission was founded on carefully derived objectives, led by decisive and flexible management, implemented by an exceptionally talented and dedicated workforce, and supported by a thorough independent review team. Other major success factors include the use of proven heritage hardware, a robust System Integration Laboratory, multi-NASA center and contractor team, concurrent operations, efficient vehicle assembly, effective risk management, and decentralized element development with a centralized control board. Ares I-X was a technically complex test that

  15. Cyclooxygenase-2/carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells

    PubMed Central

    Sansone, Pasquale; Piazzi, Giulia; Paterini, Paola; Strillacci, Antonio; Ceccarelli, Claudio; Minni, Francesco; Biasco, Guido; Chieco, Pasquale; Bonafè, Massimiliano

    2009-01-01

    Inflammation promotes colorectal carcinogenesis. Tumour growth often generates a hypoxic environment in the inner tumour mass. We here report that, in colon cancer cells, the expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) associates with that of the hypoxia response gene carbonic anhydrase-IX (CA-IX). The COX-2 knockdown, achieved by the stable infection of a COX-2 specific short harpin RNA interference (shCOX-2), down-regulates CA-IX gene expression. In colorectal cancer (CRC) cells, PGE2, the main COX-2 gene products, promotes CA-IX gene expression by ERK1/2 activation. In normoxic environment, shCOX-2 infected/CA-IX siRNA transfected CRC cells show a reduced level of active metalloproteinase-2 (MMP-2) that associates with a decreased extracellular matrix invasion capacity. In presence of hypoxia, COX-2 gene expression and PGE2 production increase. The knockdown of COX-2/CA-IX blunts the survival capability of CRC cells in hypoxia. At a high cell density, a culture condition that creates a mild pericellular hypoxic environment, the expression of COX-2/CA-IX genes is increased and triggers the invasive potential of colon cancer cells. In human colon cancer tissues, COX-2/CA-IX protein expression levels, assessed by Western blot and immunohistochemistry, correlate each other and increase with tumour stage. In conclusion, these data indicate that COX-2/CA-IX interplay promotes the aggressive behaviour of CRC cells. PMID:19017360

  16. Loop quantum cosmology of Bianchi IX: effective dynamics

    NASA Astrophysics Data System (ADS)

    Corichi, Alejandro; Montoya, Edison

    2017-03-01

    We study solutions to the effective equations for the Bianchi IX class of spacetimes within loop quantum cosmology (LQC). We consider Bianchi IX models whose matter content is a massless scalar field, by numerically solving the loop quantum cosmology effective equations, with and without inverse triad corrections. The solutions are classified using certain geometrically motivated classical observables. We show that both effective theories—with lapse N  =  V and N  =  1—resolve the big bang singularity and reproduce the classical dynamics far from the bounce. Moreover, due to the positive spatial curvature, there is an infinite number of bounces and recollapses. We study the limit of large field momentum and show that both effective theories reproduce the same dynamics, thus recovering general relativity. We implement a procedure to identify amongst the Bianchi IX solutions, those that behave like k  =  0,1 FLRW as well as Bianchi I, II, and VII0 models. The effective solutions exhibit Bianchi I phases with Bianchi II transitions and also Bianchi VII0 phases, which had not been studied before. We comment on the possible implications of these results for a quantum modification to the classical BKL behaviour.

  17. Zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, Jr., Philip N.

    1989-01-01

    An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.

  18. "What Do I Think about Title IX?" Voices from a University Community

    ERIC Educational Resources Information Center

    Paule-Koba, Amanda L.; Harris, Othello; Freysinger, Valeria J.

    2013-01-01

    Despite the apparent benefits of Title IX, the implementation of the law remains controversial, and there are divergent beliefs regarding its impact on collegiate sport. The purpose of this study was to examine how members of a university community, whose intercollegiate sport programs have changed, perceive and make sense of Title IX and the…

  19. Operational Lessons Learned from the Ares I-X Flight Test

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.

    2010-01-01

    The Ares I-X flight test, launched in 2009, is the first test of the Ares I crew launch vehicle. This development flight test evaluated the flight dynamics, roll control, and separation events, but also provided early insights into logistical, stacking, launch, and recovery operations for Ares I. Operational lessons will be especially important for NASA as the agency makes the transition from the Space Shuttle to the Constellation Program, which is designed to be less labor-intensive. The mission team itself comprised only 700 individuals over the life of the project compared to the thousands involved in Shuttle and Apollo missions; while missions to and beyond low-Earth orbit obviously will require additional personnel, this lean approach will serve as a model for future Constellation missions. To prepare for Ares I-X, vehicle stacking and launch infrastructure had to be modified at Kennedy Space Center's Vehicle Assembly Building (VAB) as well as Launch Complex (LC) 39B. In the VAB, several platforms and other structures designed for the Shuttle s configuration had to be removed to accommodate the in-line, much taller Ares I-X. Vehicle preparation activities resulted in delays, but also in lessons learned for ground operations personnel, including hardware deliveries, cable routing, transferred work and custodial paperwork. Ares I-X also proved to be a resource challenge, as individuals and ground service equipment (GSE) supporting the mission also were required for Shuttle or Atlas V operations at LC 40/41 at Cape Canaveral Air Force Station. At LC 39B, several Shuttle-specific access arms were removed and others were added to accommodate the in-line Ares vehicle. Ground command, control, and communication (GC3) hardware was incorporated into the Mobile Launcher Platform (MLP). The lightning protection system at LC 39B was replaced by a trio of 600-foot-tall towers connected by a catenary wire to account for the much greater height of the vehicle. Like Shuttle

  20. Formation of Mg-Containing Chlorophyll Precursors from Protoporphyrin IX, δ-Aminolevulinic Acid, and Glutamate in Isolated, Photosynthetically Competent, Developing Chloroplasts 1

    PubMed Central

    Fufsler, Thomas P.; Castelfranco, Paul A.; Wong, Yum-Shing

    1984-01-01

    Intact developing chloroplasts isolated from greening cucumber (Cucumis sativus L. var Beit Alpha) cotyledons were found to contain all the enzymes necessary for the synthesis of chlorophyllide. Glutamate was converted to Mg-protoporphyrin IX (monomethyl ester) and protoclorophyllide. δ-Aminolevulinic acid and protoporphyrin IX were converted to Mg-protoporphyrin IX, Mg-protoporphyrin IX monomethyl ester, protochlorophyllide and chlorophyllide a. The conversion of δ-aminolevulinic acid or protoporphyrin IX to Mg-protoporphyrin IX (monomethyl ester) was inhibited by AMP and p-chloromercuribenzene sulfonate. Light stimulated the formation of Mg-protoporphyrin IX from all three substrates. In the case of δ-aminolevulinic acid and protoporphyrin IX, light could be replaced by exogenous ATP. In the case of glutamate, both ATP and reducing power were necessary to replace light. With all three substrates, glutamate, δ-aminolevulinic acid, and protoporphyrin IX, the stimulation of Mg-protoporphyrin IX accumulation in the light was abolished by DCMU, and this DCMU block was overcome by added ATP and reducing power. PMID:16663535

  1. The Impact of Implementing Title IX in a Predominantly Black Public University.

    ERIC Educational Resources Information Center

    Simmons, Gertrude L.

    Information on the impact of implementing Title IX of the 1972 Education Amendments at Florida A and M University, a predominantly Black public university, is presented. Title IX assures everyone regardless of sex an equal opportunity to learn a skill, choose a course of study, advance in status, participate in a sport, receive a scholarship, or…

  2. Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.

    PubMed

    Hagstrom, J N; Couto, L B; Scallan, C; Burton, M; McCleland, M L; Fields, P A; Arruda, V R; Herzog, R W; High, K A

    2000-04-15

    Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)

  3. Synthesis and Biological Evaluation of 4-Sulfamoylphenyl/Sulfocoumarin Carboxamides as Selective Inhibitors of Carbonic Anhydrase Isoforms hCA II, IX, and XII.

    PubMed

    Angapelly, Srinivas; Angeli, Andrea; Khan, Arbaj Jabbar; Sri Ramya, P V; Supuran, Claudiu T; Arifuddin, Mohammed

    2018-04-19

    With the aim to develop potent and selective human carbonic anhydrase inhibitors (hCAIs), we synthesized 4-sulfamoylphenyl/sulfocoumarin benzamides (series 5 a-r and series 7 a-q) and evaluated their inhibition profiles against five isoforms of the zinc-containing human carbonic anhydrase (hCA, EC 4.2.1.1): cytosolic hCA I and II, and the transmembrane isozymes hCA IV, IX, and XII. Compounds 5 a-r were found to selectively inhibit hCA II in the nanomolar range, while being less effective against the other hCA isoforms. As noted from the literature, sulfocoumarin (1,2-benzoxathiine 2,2-dioxide) acts as a "prodrug" inhibitor and is hydrolyzed by the esterase activity of hCA to form 2-hydroxyphenylvinylsulfonic acid, which thereafter binds to the enzyme in a manner similar to that of coumarins and sulfoxocoumarins. All these sulfocoumarins (compounds 7 a-q) were found to be very weak or ineffective as inhibitors of the housekeeping off-target hCA isoforms I and II, and effectively inhibited the transmembrane tumor-associated isoforms IX and XII in the high nanomolar to micromolar ranges. Further structural modifications of these molecules could be useful for the development of effective hCA inhibitors used for the treatment of glaucoma, epilepsy, and cancer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Identification of Bisindolylmaleimide IX as a potential agent to treat drug-resistant BCR-ABL positive leukemia

    PubMed Central

    Liu, Huijuan; Zang, Yi; Azam, Mohammad; Habib, Samy L.; Li, Jia; Ruan, Xinsen; Jia, Hao; Wang, Xueying; Li, Baojie

    2016-01-01

    Chronic myeloid leukemia (CML) treatment with BCR-ABL inhibitors is often hampered by development of drug resistance. In a screen for novel chemotherapeutic drug candidates with genotoxic activity, we identified a bisindolylmaleimide derivative, IX, as a small molecule compound with therapeutic potential against CML including drug-resistant CML. We show that Bisindolylmaleimide IX inhibits DNA topoisomerase, generates DNA breaks, activates the Atm-p53 and Atm-Chk2 pathways, and induces cell cycle arrest and cell death. Interestingly, Bisindolylmaleimide IX is highly effective in targeting cells positive for BCR-ABL. BCR-ABL positive cells display enhanced DNA damage and increased cell cycle arrest in response to Bisindolylmaleimide IX due to decreased expression of topoisomerases. Cells positive for BCR-ABL or drug-resistant T315I BCR-ABL also display increased cytotoxicity since Bisindolylmaleimide IX inhibits B-Raf and the downstream oncogene addiction pathway. Mouse cancer model experiments showed that Bisindolylmaleimide IX, at doses that show little side effect, was effective in treating leukemia-like disorders induced by BCR-ABL or T315I BCR-ABL, and prolonged the lifespan of these model mice. Thus, Bisindolylmaleimide IX presents a novel drug candidate to treat drug-resistant CML via activating BCR-ABL-dependent genotoxic stress response and inhibiting the oncogene addiction pathway activated by BCR-ABL. PMID:27564101

  5. Differentiation of embryonic stem cells into hepatocytes that coexpress coagulation factors VIII and IX.

    PubMed

    Cao, Jun; Shang, Chang-zhen; Lü, Li-hong; Qiu, De-chuan; Ren, Meng; Chen, Ya-jin; Min, Jun

    2010-11-01

    To establish an efficient culture system to support embryonic stem (ES) cell differentiation into hepatocytes that coexpress F-VIII and F-IX. Mouse E14 ES cells were cultured in differentiation medium containing sodium butyrate (SB), basic fibroblast growth factor (bFGF), and/or bone morphogenetic protein 4 (BMP4) to induce the differentiation of endoderm cells and hepatic progenitor cells. Hepatocyte growth factor, oncostatin M, and dexamethasone were then used to induce the maturation of ES cell-derived hepatocytes. The mRNA expression levels of endoderm-specific genes and hepatocyte-specific genes, including the levels of F-VIII and F-IX, were detected by RT-PCR and real-time PCR during various stages of differentiation. Protein expression was examined by immunofluorescence and Western blot. At the final stage of differentiation, flow cytometry was performed to determine the percentage of cells coexpressing F-VIII and F-IX, and ELISA was used to detect the levels of F-VIII and F-IX protein secreted into the culture medium. The expression of endoderm-specific and hepatocyte-specific markers was upregulated to highest level in response to the combination of SB, bFGF, and BMP4. Treatment with the three inducers during hepatic progenitor differentiation significantly enhanced the mRNA and protein levels of F-VIII and F-IX in ES cell-derived hepatocytes. More importantly, F-VIII and F-IX were coexpressed with high efficiency at the final stage of differentiation, and they were also secreted into the culture medium. We have established a novel in vitro differentiation protocol for ES-derived hepatocytes that coexpress F-VIII and F-IX that may provide a foundation for stem cell replacement therapy for hemophilia.

  6. Development of a poly (ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation

    PubMed Central

    Ma, Hongyan; Darmawan, Erica T.; Zhang, Min; Zhange, Lei; Bryers, James D.

    2013-01-01

    Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, surplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly (ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3 months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. PMID:24140747

  7. Development of a poly(ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation.

    PubMed

    Ma, Hongyan; Darmawan, Erica T; Zhang, Min; Zhang, Lei; Bryers, James D

    2013-12-28

    Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, supplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly(ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. © 2013.

  8. Platelet Glycoprotein Ib-IX and Malignancy

    DTIC Science & Technology

    2010-09-01

    provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin - rich network produced by coagulation...process and can initiate the formation of a platelet - rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib... Platelet Glycoprotein Ib-IX and Malignancy PRINCIPAL INVESTIGATOR: Jerry Ware, Ph.D

  9. Title IX Enforcement Called 'Deeply Troubling'

    ERIC Educational Resources Information Center

    Lipka, Sara; Wolverton, Brad

    2007-01-01

    The government agency responsible for enforcing gender equity in college sports is falling down on the job, according to a report released by the National Women's Law Center. Over the past five years, the U.S. Education Department's Office for Civil Rights -- the administrative guardian of Title IX of the Education Amendments of 1972, the law that…

  10. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... the meeting is for Business Organizations, Trade Associations, Chambers of Commerce and related... SMALL BUSINESS ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX... hereby given that the U.S. Small Business Administration (SBA) Region IX Regulatory Fairness Board and...

  11. Zinc Absorption by Young Adults from Supplemental Zinc Citrate Is Comparable with That from Zinc Gluconate and Higher than from Zinc Oxide123

    PubMed Central

    Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnić, Marica; Hurrell, Richard F.

    2014-01-01

    The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with 67Zn and 70Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6–71.0) and was not different from that from zinc gluconate with 60.9% (50.6–71.7). Absorption from zinc oxide at 49.9% (40.9–57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627. PMID:24259556

  12. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.

    PubMed

    Hemilä, Harri

    2017-05-01

    To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect. Meta-analysis. Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method. Seven randomised trials with 575 participants with naturally acquired common colds. Duration of the common cold. The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32). Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further.

  13. Dietary phytate, zinc and hidden zinc deficiency.

    PubMed

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Ares I-X Post Flight Ignition Overpressure Review

    NASA Technical Reports Server (NTRS)

    Alvord, David A.

    2010-01-01

    Ignition Overpressure (IOP) is an unsteady fluid flow and acoustic phenomena caused by the rapid expansion of gas from the rocket nozzle within a ducted launching space resulting in an initially higher amplitude pressure wave. This wave is potentially dangerous to the structural integrity of the vehicle. An in-depth look at the IOP environments resulting from the Ares I-X Solid Rocket Booster configuration showed high correlation between the pre-flight predictions and post-flight analysis results. Correlation between the chamber pressure and IOP transients showed successful acoustic mitigation, containing the strongest IOP waves below the Mobile Launch Pad deck. The flight data allowed subsequent verification and validation of Ares I-X unsteady fluid ducted launcher predictions, computational fluid dynamic models, and strong correlation with historical Shuttle data.

  15. A Perspective on Development Flight Instrumentation and Flight Test Analysis Plans for Ares I-X

    NASA Technical Reports Server (NTRS)

    Huebner, Lawrence D.; Richards, James S.; Brunty, Joseph A.; Smith, R. Marshall; Trombetta, Dominic R.

    2009-01-01

    NASA. s Constellation Program will take a significant step toward completion of the Ares I crew launch vehicle with the flight test of Ares I-X and completion of the Ares I-X post-flight evaluation. The Ares I-X flight test vehicle is an ascent development flight test that will acquire flight data early enough to impact the design and development of the Ares I. As the primary customer for flight data from the Ares I-X mission, Ares I has been the major driver in the definition of the Development Flight Instrumentation (DFI). This paper focuses on the DFI development process and the plans for post-flight evaluation of the resulting data to impact the Ares I design. Efforts for determining the DFI for Ares I-X began in the fall of 2005, and significant effort to refine and implement the Ares I-X DFI has been expended since that time. This paper will present a perspective in the development and implementation of the DFI. Emphasis will be placed on the process by which the list was established and changes were made to that list due to imposed constraints. The paper will also discuss the plans for the analysis of the DFI data following the flight and a summary of flight evaluation tasks to be performed in support of tools and models validation for design and development.

  16. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    NASA Astrophysics Data System (ADS)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  17. Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

    PubMed

    Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

    2015-12-01

    A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

  18. Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma.

    PubMed

    Belykh, Evgenii; Miller, Eric J; Hu, Danying; Martirosyan, Nikolay L; Woolf, Eric C; Scheck, Adrienne C; Byvaltsev, Vadim A; Nakaji, Peter; Nelson, Leonard Y; Seibel, Eric J; Preul, Mark C

    2018-05-01

    Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Zinc Enzymes.

    ERIC Educational Resources Information Center

    Bertini, I.; And Others

    1985-01-01

    Discusses the role of zinc in various enzymes concerned with hydration, hydrolysis, and redox reactions. The binding of zinc to protein residues, properties of noncatalytic zinc(II) and catalytic zinc, and the reactions catalyzed by zinc are among the topics considered. (JN)

  20. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response.

    PubMed

    Manno, Catherine S; Pierce, Glenn F; Arruda, Valder R; Glader, Bertil; Ragni, Margaret; Rasko, John J; Rasko, John; Ozelo, Margareth C; Hoots, Keith; Blatt, Philip; Konkle, Barbara; Dake, Michael; Kaye, Robin; Razavi, Mahmood; Zajko, Albert; Zehnder, James; Rustagi, Pradip K; Nakai, Hiroyuki; Chew, Amy; Leonard, Debra; Wright, J Fraser; Lessard, Ruth R; Sommer, Jürg M; Tigges, Michael; Sabatino, Denise; Luk, Alvin; Jiang, Haiyan; Mingozzi, Federico; Couto, Linda; Ertl, Hildegund C; High, Katherine A; Kay, Mark A

    2006-03-01

    We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 x 10(12) vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of approximately 8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.

  1. Ares I-X Ground Diagnostic Prototype

    NASA Technical Reports Server (NTRS)

    Schwabacher, Mark; Martin, Rodney; Waterman, Robert; Oostdyk, Rebecca; Ossenfort, John; Matthews, Bryan

    2010-01-01

    Automating prelaunch diagnostics for launch vehicles offers three potential benefits. First, it potentially improves safety by detecting faults that might otherwise have been missed so that they can be corrected before launch. Second, it potentially reduces launch delays by more quickly diagnosing the cause of anomalies that occur during prelaunch processing. Reducing launch delays will be critical to the success of NASA's planned future missions that require in-orbit rendezvous. Third, it potentially reduces costs by reducing both launch delays and the number of people needed to monitor the prelaunch process. NASA is currently developing the Ares I launch vehicle to bring the Orion capsule and its crew of four astronauts to low-earth orbit on their way to the moon. Ares I-X will be the first unmanned test flight of Ares I. It is scheduled to launch on October 27, 2009. The Ares I-X Ground Diagnostic Prototype is a prototype ground diagnostic system that will provide anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage thrust vector control (TVC) and for the associated ground hydraulics while it is in the Vehicle Assembly Building (VAB) at John F. Kennedy Space Center (KSC) and on the launch pad. It will serve as a prototype for a future operational ground diagnostic system for Ares I. The prototype combines three existing diagnostic tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool that is commercially produced by Qualtech Systems, Inc. It uses a qualitative model of failure propagation to perform fault isolation and diagnostics. We adapted an existing TEAMS model of the TVC to use for diagnostics and developed a TEAMS model of the ground hydraulics. The second tool, Spacecraft Health Inference Engine (SHINE), is a rule-based expert system developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification. The prototype

  2. An Annotated Summary of the Regulation for Title IX Education Amendments of 1972.

    ERIC Educational Resources Information Center

    NETWORK, Inc., Andover, MA.

    This document is one of a two-part set of publications. Both deal with equal education and provide a concise overview of Title IX and gender equity issues in education and steps to take to ensure nondiscrimination and equal education opportunity for all. Title IX of the Education Amendments of 1972 is the major federal law prohibiting sex…

  3. Zinc

    MedlinePlus

    ... Using toothpastes containing zinc, with or without an antibacterial agent, appears to prevent plaque and gingivitis. Some ... is some evidence that zinc has some antiviral activity against the herpes virus. Low zinc levels can ...

  4. Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas: standardization and quantitative comparison with histology

    NASA Astrophysics Data System (ADS)

    Wei, Linpeng; Chen, Ye; Yin, Chengbo; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T. C.

    2017-04-01

    Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image contrast in many tumors due to the increased accumulation of protoporphyrin IX (PpIX), a fluorescent porphyrin that is associated with tumor burden and proliferation. The value of PpIX-guided resection of malignant gliomas has been demonstrated in prospective randomized clinical studies in which a twofold greater extent of resection and improved progression-free survival have been observed. In low-grade gliomas and at the diffuse infiltrative margins of all gliomas, PpIX fluorescence is often too weak to be detected with current low-resolution surgical microscopes that are used in operating rooms. However, it has been demonstrated that high-resolution optical-sectioning microscopes are capable of detecting the sparse and punctate accumulations of PpIX that are undetectable via conventional low-power surgical fluorescence microscopes. To standardize the performance of high-resolution optical-sectioning devices for future clinical use, we have developed an imaging phantom and methods to ensure that the imaging of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging studies with a dual-axis confocal microscope demonstrate that these methods enable the acquisition of images from unsectioned human brain tissues that quantitatively and consistently correlate with images of histologically processed tissue sections.

  5. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

    NASA Astrophysics Data System (ADS)

    Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

    2014-07-01

    Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

  6. Core-shell AgSiO2-protoporphyrin IX nanoparticle: Effect of the Ag core on reactive oxygen species generation

    NASA Astrophysics Data System (ADS)

    Lismont, M.; Pá; ez-Martinez, C.; Dreesen, L.

    2015-03-01

    Photodynamic therapy (PDT) for cancer is based on the use of a light sensitive molecule to produce, under specific irradiation, toxic reactive oxygen species (ROS). A way to improve the therapy efficiency is to increase the amount of produced ROS near cancer cells. This aim can be achieved by using a metal enhanced process arising when an optically active molecule is located near a metallic nanoparticle (NP). Here, the coupling effect between silver (Ag) NPs and protoporphyrin IX (PpIX) molecules, a clinically approved photosensitizer, is studied compared first, to PpIX fluorescence yield and second, to ROS production efficiency. By applying a modified Stöber process, PpIX was encapsulated into a silica (SiO2) shell, surrounding a 60 nm sized Ag core. We showed that, compared to SiO2-PpIX NPs, Ag coated SiO2-PpIX NPs dramatically decreased PpIX fluorescence together with singlet oxygen production efficiency. However, after incubation time in the dark, the amount of superoxide anions generated by the Ag doped sample was higher than the control sample one.

  7. Influence of vector dose on factor IX-specific T and B cell responses in muscle-directed gene therapy.

    PubMed

    Herzog, Roland W; Fields, Paul A; Arruda, Valder R; Brubaker, Jeff O; Armstrong, Elina; McClintock, Darryl; Bellinger, Dwight A; Couto, Linda B; Nichols, Timothy C; High, Katherine A

    2002-07-20

    Intramuscular injection of an adeno-associated virus (AAV) vector has resulted in vector dose-dependent, stable expression of canine factor IX (cF.IX) in hemophilia B dogs with an F.IX missense mutation (Herzog et al., Nat. Med. 1999;5:56-63). The use of a species-specific transgene allowed us to study risks and characteristics of antibody formation against the therapeutic transgene product. We analyzed seven dogs that had been injected at a single time point at multiple intramuscular sites with varying vector doses (dose per kilogram, dose per animal, dose per site). Comparison of individual animals suggests an increased likelihood of inhibitory anti-cF.IX (inhibitor) development with increased vector doses, with dose per site showing the strongest correlation with the risk of inhibitor formation. In six of seven animals, such immune responses were either absent or transient, and therefore did not prevent sustained systemic expression of cF.IX. Transient inhibitory/neutralizing anti-cF.IX responses occurred at vector doses of 2 x 10(12)/site, whereas a 6-fold higher dose resulted in a longer lasting, higher titer inhibitor. Anti-cF.IX was efficiently blocked in an eighth animal that was injected with a high vector dose per site, but in addition received transient immune suppression. Inhibitor formation was characterized by synthesis of two IgG subclasses and in vitro proliferation of lymphocytes to cF.IX antigen, indicating a helper T cell-dependent mechanism. Anti-cF.IX formation is likely influenced by the extent of local antigen presentation and may be avoided by limited vector doses or by transient immune modulation.

  8. Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

    PubMed Central

    Valdés, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Fan, Xiaoyao; Tosteson, Tor D.; Hartov, Alex; Ji, Songbai; Erkmen, Kadir; Simmons, Nathan E.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of

  9. Sex Discrimination Against Students: Implications of Title IX of the Education Amendments of 1972.

    ERIC Educational Resources Information Center

    Dunkle, Margaret C.; Sandler, Bernice

    Title IX of the Education Amendments of 1972 mandates that sex discrimination be eliminated in federally assisted education programs. Title IX has significant implications for a variety of issues including recruiting, admissions, financial aid, student rules and regulations, housing rules, health care and insurance benefits, student employment,…

  10. Title IX Compliance at Two-Year Colleges: An Analysis of Perceived Barriers and Strategies

    ERIC Educational Resources Information Center

    Causby, Cory Scott

    2010-01-01

    Although Title IX legislation has been in effect since 1972 and has created unprecedented positive change on intercollegiate athletics, educational institutions have still had difficulty meeting the basic requirements set forth by Title IX and ensuring gender equity in their athletic programs. Additionally, specific research has been largely…

  11. Feminizing Science: The Alchemy of Title IX

    ERIC Educational Resources Information Center

    Hausman, Patricia

    2008-01-01

    The author scrutinizes the National Academy of Sciences report "Beyond Bias and Barriers: Fulfilling the Potential of Women in Academic Science and Engineering" and its dangerous call to place the sciences under the sledgehammer of Title IX. Her findings: A one-sided, inaccurate, and internally contradictory report prepared by a…

  12. Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.

    PubMed

    Nakai, Yasushi; Tatsumi, Yoshihiro; Miyake, Makito; Anai, Satoshi; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

    2016-03-01

    The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells. Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis. The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology. The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Ares I-X: First Step in a New Era of Exploration

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.

    2010-01-01

    Since 2005, NASA's Constellation Program has been designing, building, and testing the next generation of launch and space vehicles to carry humans beyond low-Earth orbit (LEO). On October 28, 2009, the Ares Projects successfully launched the first suborbital development flight test of the Ares I crew launch vehicle, Ares I-X, from Kennedy Space Center (KSC). Although the final Constellation Program architecture is under review, data and lessons obtained from Ares I-X can be applied to any launch vehicle. This presentation will discuss the mission background and future impacts of the flight. Ares I is designed to carry up to four astronauts to the International Space Station (ISS). It also can be used with the Ares V cargo launch vehicle for a variety of missions beyond LEO. The Ares I-X development flight test was conceived in 2006 to acquire early engineering, operations, and environment data during liftoff, ascent, and first stage recovery. Engineers are using the test flight data to improve the Ares I design before its critical design review the final review before manufacturing of the flight vehicle begins. The Ares I-X flight test vehicle incorporated a mix of flight and mockup hardware, reflecting a similar length and mass to the operational vehicle. It was powered by a four-segment SRB from the Space Shuttle inventory, and was modified to include a fifth, spacer segment that made the booster approximately the same size as the five-segment SRB. The Ares I-X flight closely approximated flight conditions the Ares I will experience through Mach 4.5, performing a first stage separation at an altitude of 125,000 feet and reaching a maximum dynamic pressure ("Max Q") of approximately 850 pounds per square foot. The Ares I-X Mission Management Office (MMO) was organized functionally to address all the major test elements, including: first stage, avionics, and roll control (Marshall Space Flight Center); upper stage simulator (Glenn Research Center); crew module

  14. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

    PubMed Central

    Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

    2014-01-01

    Abstract. Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response. PMID:24996661

  15. Ares I-X Thermal Model Correlation and Lessons Learned

    NASA Technical Reports Server (NTRS)

    Amundsen, Ruth M.

    2010-01-01

    The Ares I-X vehicle launched and flew successfully on October 28, 2009. This paper will describe the correlation of the vehicle thermal model to both ground testing and flight data. A main purpose of the vehicle model and ground testing was to ensure that the avionics within the vehicle were held within their thermal limits prior to launch and during flight. The correlation of the avionics box temperatures will be shown. Also, the lessons learned in the thermal discipline during the modeling, test, correlation to test, and flight of the Ares I-X flight test vehicle will be described. Lessons learned will cover thermal modeling, as well as management of the thermal discipline, thermal team, and thermal-related actions in design, testing, and flight.

  16. White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Flynn, Brendan P.; DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2013-04-01

    Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

  17. Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Baran, Christine; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

    2009-02-01

    Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

  18. [Improvement in zinc nutrition due to zinc transporter-targeting strategy].

    PubMed

    Kambe, Taiho

    2016-07-01

    Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

  19. Ares I-X Test Flight Reference Trajectory Development

    NASA Technical Reports Server (NTRS)

    Starr, Brett R.; Gumbert, Clyde R.; Tartabini, Paul V.

    2011-01-01

    Ares I-X was the first test flight of NASA's Constellation Program's Ares I crew launch vehicle. Ares I is a two stage to orbit launch vehicle that provides crew access to low Earth orbit for NASA's future manned exploration missions. The Ares I first stage consists of a Shuttle solid rocket motor (SRM) modified to include an additional propellant segment and a liquid propellant upper stage with an Apollo J2X engine modified to increase its thrust capability. The modified propulsion systems were not available for the first test flight, thus the test had to be conducted with an existing Shuttle 4 segment reusable solid rocket motor (RSRM) and an inert Upper Stage. The test flight's primary objective was to demonstrate controllability of an Ares I vehicle during first stage boost and the ability to perform a successful separation. In order to demonstrate controllability, the Ares I-X ascent control algorithms had to maintain stable flight throughout a flight environment equivalent to Ares I. The goal of the test flight reference trajectory development was to design a boost trajectory using the existing RSRM that results in a flight environment equivalent to Ares I. A trajectory similarity metric was defined as the integrated difference between the Ares I and Ares I-X Mach versus dynamic pressure relationships. Optimization analyses were performed that minimized the metric by adjusting the inert upper stage weight and the ascent steering profile. The sensitivity of the optimal upper stage weight and steering profile to launch month was also investigated. A response surface approach was used to verify the optimization results. The analyses successfully defined monthly ascent trajectories that matched the Ares I reference trajectory dynamic pressure versus Mach number relationship to within 10% through Mach 3.5. The upper stage weight required to achieve the match was found to be feasible and varied less than 5% throughout the year. The paper will discuss the flight

  20. Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models

    PubMed Central

    Konecky, Soren D.; Owen, Chris M.; Rice, Tyler; Valdés, Pablo A.; Kolste, Kolbein; Wilson, Brian C.; Leblond, Frederic; Roberts, David W.; Paulsen, Keith D.

    2012-01-01

    Abstract. Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼1.5 in reduced scattering coefficient for all wavelengths and was ∼1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors. PMID:22612131

  1. CLVTOPS Liftoff and Separation Analysis Validation Using Ares I-X Flight Data

    NASA Technical Reports Server (NTRS)

    Burger, Ben; Schwarz, Kristina; Kim, Young

    2011-01-01

    CLVTOPS is a multi-body time domain flight dynamics simulation tool developed by NASA s Marshall Space Flight Center (MSFC) for a space launch vehicle and is based on the TREETOPS simulation tool. CLVTOPS is currently used to simulate the flight dynamics and separation/jettison events of the Ares I launch vehicle including liftoff and staging separation. In order for CLVTOPS to become an accredited tool, validation against other independent simulations and real world data is needed. The launch of the Ares I-X vehicle (first Ares I test flight) on October 28, 2009 presented a great opportunity to provide validation evidence for CLVTOPS. In order to simulate the Ares I-X flight, specific models were implemented into CLVTOPS. These models include the flight day environment, reconstructed thrust, reconstructed mass properties, aerodynamics, and the Ares I-X guidance, navigation and control models. The resulting simulation output was compared to Ares I-X flight data. During the liftoff region of flight, trajectory states from the simulation and flight data were compared. The CLVTOPS results were used to make a semi-transparent animation of the vehicle that was overlaid directly on top of the flight video to provide a qualitative measure of the agreement between the simulation and the actual flight. During ascent, the trajectory states of the vehicle were compared with flight data. For the stage separation event, the trajectory states of the two stages were compared to available flight data. Since no quantitative rotational state data for the upper stage was available, the CLVTOPS results were used to make an animation of the two stages to show a side-by-side comparison with flight video. All of the comparisons between CLVTOPS and the flight data show good agreement. This paper documents comparisons between CLVTOPS and Ares I-X flight data which serve as validation evidence for the eventual accreditation of CLVTOPS.

  2. Constellation's First Flight Test: Ares I-X

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Askins, Bruce R.

    2010-01-01

    On October 28, 2009, NASA launched Ares I-X, the first flight test of the Constellation Program that will send human beings to the Moon and beyond. This successful test is the culmination of a three-and-a-half-year, multi-center effort to design, build, and fly the first demonstration vehicle of the Ares I crew launch vehicle, the successor vehicle to the Space Shuttle. The suborbital mission was designed to evaluate the atmospheric flight characteristics of a vehicle dynamically similar to Ares I; perform a first stage separation and evaluate its effects; characterize and control roll torque; stack, fly, and recover a solid-motor first stage testing the Ares I parachutes; characterize ground, flight, and reentry environments; and develop and execute new ground hardware and procedures. Built from existing flight and new simulator hardware, Ares I-X integrated a Shuttle-heritage four-segment solid rocket booster for first stage propulsion, a spacer segment to simulate a five-segment booster, Peacekeeper axial engines for roll control, and Atlas V avionics, as well as simulators for the upper stage, crew module, and launch abort system. The mission leveraged existing logistical and ground support equipment while also developing new ones to accommodate the first in-line rocket for flying astronauts since the Saturn IB last flew from Kennedy Space Center (KSC) in 1975. This paper will describe the development and integration of the various vehicle and ground elements, from conception to stacking in KSC s Vehicle Assembly Building; hardware performance prior to, during, and after the launch; and preliminary lessons and data gathered from the flight. While the Constellation Program is currently under review, Ares I-X has and will continue to provide vital lessons for NASA personnel in taking a vehicle concept from design to flight.

  3. An intraoperative spectroscopic imaging system for quantification of Protoporphyrin IX during glioma surgery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Angulo-Rodríguez, Leticia M.; Laurence, Audrey; Jermyn, Michael; Sheehy, Guillaume; Sibai, Mira; Petrecca, Kevin; Roberts, David W.; Paulsen, Keith D.; Wilson, Brian C.; Leblond, Frédéric

    2016-03-01

    Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.

  4. Ares I-X Launch Vehicle Modal Test Measurements and Data Quality Assessments

    NASA Technical Reports Server (NTRS)

    Templeton, Justin D.; Buehrle, Ralph D.; Gaspar, James L.; Parks, Russell A.; Lazor, Daniel R.

    2010-01-01

    The Ares I-X modal test program consisted of three modal tests conducted at the Vehicle Assembly Building at NASA s Kennedy Space Center. The first test was performed on the 71-foot 53,000-pound top segment of the Ares I-X launch vehicle known as Super Stack 5 and the second test was performed on the 66-foot 146,000- pound middle segment known as Super Stack 1. For these tests, two 250 lb-peak electro-dynamic shakers were used to excite bending and shell modes with the test articles resting on the floor. The third modal test was performed on the 327-foot 1,800,000-pound Ares I-X launch vehicle mounted to the Mobile Launcher Platform. The excitation for this test consisted of four 1000+ lb-peak hydraulic shakers arranged to excite the vehicle s cantilevered bending modes. Because the frequencies of interest for these modal tests ranged from 0.02 to 30 Hz, high sensitivity capacitive accelerometers were used. Excitation techniques included impact, burst random, pure random, and force controlled sine sweep. This paper provides the test details for the companion papers covering the Ares I-X finite element model calibration process. Topics to be discussed include test setups, procedures, measurements, data quality assessments, and consistency of modal parameter estimates.

  5. Providing Transparency to the Title IX Process

    ERIC Educational Resources Information Center

    Hartle, Terry

    2017-01-01

    When U.S. Secretary of Education Betsy DeVos announced Sept. 7, 2017, that her department would revisit how Title IX rules are enforced with respect to campus sexual assault, she said the first step would be a "transparent notice and comment process" to replace the 2011 "guidance" (and follow up 2014 guidance) that has been…

  6. Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

    PubMed Central

    Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

    2015-01-01

    OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were

  7. Electron Impact Exciation of Fe IX

    NASA Astrophysics Data System (ADS)

    Tayal, Swaraj; Zatsarinny, Oleg

    2015-05-01

    Transition probabilities and electron impact excitation collision strengths and rates for astrophysically important extreme ultraviolet lines of Fe IX are calculated. The 322 fine-structure levels of the 3s2 3p6 , 3s2 3p5 3 d , 3 s 3p6 3 d , 3s2 3p5 4 s , and 3s2 3p4 3d2 configurations are included in our calculations. The collision strengths have been calculated using the B-spline Breit-Pauli R-matrix method for all fine-structure transitions among the 322 levels. The mass, Darwin, and spin-orbit relativistic effects are included in the Breit-Pauli Hamiltonian in the scattering calculation. The one-body and two-body relativistic operators are included in the multi-configuration Hartree-Fock calculations of transition probabilities. Several sets of non-orthogonal spectroscopic and correlation radial orbitals are used to obtain accurate description of Fe IX levels and to represent the scattering functions. The calculated excitation energies are in very good agreement with experiment and represents an improvement over the previous calculations. The present collision strengths show reasonable agreement with the previously available R-matrix and distorted-wave calculations. This research is supported by NASA grant from the Solar and Heliophysics Program.

  8. Ares I-X Ascent Base Environments

    NASA Technical Reports Server (NTRS)

    Mobley, B. L.; Bender, R. L.; Canabal, F.; Smith, Sheldon D.

    2011-01-01

    Plume induced base heating environments were measured during the flight of the NASA Constellation Ares I-X developmental launch vehicle, successfully flown on October 28, 2009. The Ares IX first stage is a four segment Space Shuttle derived booster with base consisting of a flared aft skirt, deceleration and tumble motors, and a thermal curtain surrounding the first stage 7.2 area ratio nozzle. Developmental Flight Instrumentation (DFI) consisted of radiometers, calorimeters, pressure transducers and gas temperature probes installed on the aft skirt and nozzle to measure the base environments. In addition, thermocouples were also installed between the layers of the flexible thermal curtain to provide insight into the curtain response to the base environments and to assist in understanding curtain failure during reentry. Plume radiation environment predictions were generated by the Reverse Monte Carlo (RMC) code and the convective base heating predictions utilized heritage MSFC empirical methods. These predictions were compared to the DFI data and results from the flight videography. Radiation predictions agreed with the flight measured data early in flight but gauge failures prevented high altitude comparisons. The convective environment comparisons demonstrated the need to improve the prediction methodology; particularly for low altitude, local plume recirculation. The convective comparisons showed relatively good agreement at altitudes greater than 50,000 feet.

  9. Improved zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, P.N. Jr.

    1988-06-21

    The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

  10. National Environmental/Energy Workforce Assessment for Region IX.

    ERIC Educational Resources Information Center

    National Field Research Center Inc., Iowa City, IA.

    This report represents a detailed summation of existing workforce levels, training programs, career potential, and staffing level projections through 1981 for EPA Region IX. This region serves the states of Arizona, California, Hawaii, and Nevada. The specific pollution programs considered include air, noise, pesticides, potable water, radiation…

  11. Hantavirus Prevalence in the IX Region of Chile

    PubMed Central

    Vial, Pablo C.; Castillo, Constanza H.; Godoy, Paula M.; Hjelle, Brian; Ferrés, Marcela G.

    2003-01-01

    An epidemiologic and seroprevalence survey was conducted (n=830) to assess proportion of persons exposed to hantavirus in IX Region Chile, which accounts for 25% of reported cases of hantavirus cardiopulmonary syndrome. This region has three geographic areas with different disease incidences and a high proportion of aboriginals. Serum samples were tested for immunoglobulin (Ig) G antibodies by enzyme-linked immunosorbent assay against Sin Nombre virus N antigen by strip immunoblot assay against Sin Nombre, Puumala, Río Mamoré, and Seoul N antigens. Samples from six patients were positive for IgG antibodies reactive with Andes virus; all patients lived in the Andes Mountains. Foresting was also associated with seropositivity; but not sex, age, race, rodent exposure, or farming activities. Exposure to hantavirus varies in different communities of IX Region. Absence of history of pneumonia or hospital admission in persons with specific IgG antibodies suggests that infection is clinically inapparent. PMID:12890323

  12. Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

    PubMed Central

    Nagai, K; Nagao, M; Nagao, M; Yanai, S; Minagawa, K; Takahashi, Y; Takekoshi, Y; Ishizaka, A; Matsuzono, Y; Kobayashi, O; Itagaki, T

    1998-01-01

    We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive. Images PMID:9598735

  13. Photosensitized H2 Production Using a Zinc Porphyrin-Substituted Protein, Platinum Nanoparticles, and Ascorbate with No Electron Relay: Participation of Good's Buffers.

    PubMed

    Clark, Emily R; Kurtz, Donald M

    2017-04-17

    Development of efficient light-driven splitting of water, 2H 2 O → 2H 2 + O 2 , often attempts to optimize photosensitization of the reductive and oxidative half-reactions individually. Numerous homogeneous and heterogeneous systems have been developed for photochemical stimulation of the reductive half reaction, 2H + + 2e - → H 2 . These systems generally consist of various combinations of a H + reduction catalyst, a photosensitizer (PS), and a "sacrificial" electron donor. Zinc(II)-porphyrins (ZnPs) have frequently been used as PSs for H 2 generation, but they are subject to various self-quenching processes in aqueous solutions. Colloidal platinum in nanoparticle form (Pt NP) is a classical H + reduction catalyst using ZnP photosensitizers, but efficient photosensitized H 2 generation requires an electron relay molecule between ZnP and Pt NP. The present report describes an aqueous system for visible (white) light-sensitized generation of H 2 using a protein-embedded Zn(II)-protoporphyrin IX as PS and Pt NP as H + reduction catalyst without an added electron relay. This system operated efficiently in piperazino- and morpholino-alkylsulfonic acid (Good's buffers), which served as sacrificial electron donors. The system also required ascorbate at relatively modest concentrations, which stabilized the Zn(II)-protoporphyrin IX against photodegradation. In the absence of an electron relay molecule, the photosensitized H 2 generation must involve formation of at least a transient complex between a protein-embedded Zn(II)-protoporphyrin IX species and Pt NP.

  14. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

    PubMed

    Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

    2016-09-01

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Legal Forum: Title IX: Does It Apply to Employees?

    ERIC Educational Resources Information Center

    McCarthy, Martha

    1981-01-01

    Briefly reviews a number of Federal court cases that have dealt with Title IX, considering the issue of whether the 1974 regulations prohibiting sex discrimination in employment practices accurately reflect the intent of the 1972 law. (GC)

  16. In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

    NASA Astrophysics Data System (ADS)

    LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

    2017-02-01

    Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

  17. Title IX and Sexual Harassment of Student Athletes.

    ERIC Educational Resources Information Center

    Wolohan, John T.

    1995-01-01

    This article reviews what constitutes sexual harassment in sports by examining Title IX of the Education Amendments of 1972 and the effect it has had on charges of sexual harrassment in educational institutions. Athletic administrators are provided with strategies and recommendations to help schools and athletic departments develop sexual…

  18. Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

    PubMed

    Koizumi, N; Harada, Y; Beika, M; Minamikawa, T; Yamaoka, Y; Dai, P; Murayama, Y; Yanagisawa, A; Otsuji, E; Tanaka, H; Takamatsu, T

    2016-08-01

    The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Significant performance enhancement of inverted organic light-emitting diodes by using ZnIx as a hole-blocking layer

    NASA Astrophysics Data System (ADS)

    Cheng, Chuan-Hui; Zhang, Bi-Long; Sun, Chao; Li, Ruo-Xuan; Wang, Yuan; Tian, Wen-Ming; Zhao, Chun-Yi; Jin, Sheng-Ye; Liu, Wei-Feng; Luo, Ying-Min; Du, Guo-Tong; Cong, Shu-Lin

    2017-06-01

    A highly efficient inverted organic light emitting diode using 1.0 nm-thick ZnIx as a hole-blocking layer is developed. We fabricate devices with the configuration ITO/ZnIx (1.0 nm)/Alq3 (50 nm)/NPB (50 nm)/MoO3 (6.0 nm)/Al (100 nm). The deposition of a ZnIx layer increases the maximum luminance by two orders of magnitude from 13.4 to 3566.1 cd/m2. In addition, the maximum current efficiency and power efficiency are increased by three orders of magnitude, and the turn-on voltage to reach 1 cd/m2 decreases from 13 to 8 V. The results suggest that the electron injection efficiency is not improved by introducing a ZnIx layer. Instead, the improved device performance originates from the strong hole-blocking ability of ZnIx. This work indicates that layered materials may lead to novel applications in optoelectronic devices.

  20. Ares I-X Flight Evaluation Tasks in Support of Ares I Development

    NASA Technical Reports Server (NTRS)

    Huebner, Lawrence D.; Richards, James S.; Coates, Ralph H., III; Cruit, Wendy D.; Ramsey, Matthew N.

    2010-01-01

    NASA s Constellation Program successfully launched the Ares I-X Flight Test Vehicle on October 28, 2009. The Ares I-X flight was a development flight test that offered a unique opportunity for early engineering data to impact the design and development of the Ares I crew launch vehicle. As the primary customer for flight data from the Ares I-X mission, the Ares Projects Office established a set of 33 flight evaluation tasks to correlate fight results with prospective design assumptions and models. Included within these tasks were direct comparisons of flight data with pre-flight predictions and post-flight assessments utilizing models and modeling techniques being applied to design and develop Ares I. A discussion of the similarities and differences in those comparisons and the need for discipline-level model updates based upon those comparisons form the substance of this paper. The benefits of development flight testing were made evident by implementing these tasks that used Ares I-X data to partially validate tools and methodologies in technical disciplines that will ultimately influence the design and development of Ares I and future launch vehicles. The areas in which partial validation from the flight test was most significant included flight control system algorithms to predict liftoff clearance, ascent, and stage separation; structural models from rollout to separation; thermal models that have been updated based on these data; pyroshock attenuation; and the ability to predict complex flow fields during time-varying conditions including plume interactions.

  1. Method of capturing or trapping zinc using zinc getter materials

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

    Hunyadi Murph, Simona E.; Korinko, Paul S.

    2017-07-11

    A method of trapping or capturing zinc is disclosed. In particular, the method comprises a step of contacting a zinc vapor with a zinc getter material. The zinc getter material comprises nanoparticles and a metal substrate.

  2. The Meanings of the Preposition "By" in the IX-XIX Centuries with Their Azerbaijani Equivalents

    ERIC Educational Resources Information Center

    Anvar Ghizi, Aliyeva Shalalah

    2010-01-01

    The article deals with the meanings of the English preposition "by" in the IX-XIX centuries and their Azerbaijani equivalents. During that period the preposition "by" had more than 10 variants of writing. From the IX to the XIX centuries the preposition "by" was used in 6 main meanings: the meanings were connected…

  3. Initial Assessment of the Ares I-X Launch Vehicle Upper Stage to Vibroacoustic Flight Environments

    NASA Technical Reports Server (NTRS)

    Larko, Jeffrey M.; Hughes, William O.

    2008-01-01

    The Ares I launch vehicle will be NASA s first new launch vehicle since 1981. Currently in design, it will replace the Space Shuttle in taking astronauts to the International Space Station, and will eventually play a major role in humankind s return to the Moon and eventually to Mars. Prior to any manned flight of this vehicle, unmanned test readiness flights will be flown. The first of these readiness flights, named Ares I-X, is scheduled to be launched in April 2009. The NASA Glenn Research Center is responsible for the design, manufacture, test and analysis of the Ares I-X upper stage simulator (USS) element. As part of the design effort, the structural dynamic response of the Ares I-X launch vehicle to its vibroacoustic flight environments must be analyzed. The launch vehicle will be exposed to extremely high acoustic pressures during its lift-off and aerodynamic stages of flight. This in turn will cause high levels of random vibration on the vehicle's outer surface that will be transmitted to its interior. Critical flight equipment, such as its avionics and flight guidance components are susceptible to damage from this excitation. This study addresses the modelling, analysis and predictions from examining the structural dynamic response of the Ares I-X upper stage to its vibroacoustic excitations. A statistical energy analysis (SEA) model was used to predict the high frequency response of the vehicle at locations of interest. Key to this study was the definition of the excitation fields corresponding to lift off acoustics and the unsteady aerodynamic pressure fluctuations during flight. The predicted results will be used by the Ares I-X Project to verify the flight qualification status of the Ares I-X upper stage components.

  4. Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

    PubMed Central

    Kim, Kyungbin; Park, Won Young; Kim, Jee Yeon; Sol, Mee Young; Shin, Dong Hun; Park, Do Youn; Lee, Chang Hun; Lee, Jeong Hee

    2012-01-01

    Background Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy. PMID:23323103

  5. 26. Photocopy of August 1918 photograph. Glass Negative Box IX, ...

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

    26. Photocopy of August 1918 photograph. Glass Negative Box IX, Tower Grove, Missouri Botanical Garden. ITALIAN GARDEN, LOOKING SOUTHWEST - Missouri Botanical Garden, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

  6. Zinc in human health: effect of zinc on immune cells.

    PubMed

    Prasad, Ananda S

    2008-01-01

    Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF

  7. Ares I-X Ground Diagnostic Prototype

    NASA Technical Reports Server (NTRS)

    Schwabacher, Mark A.; Martin, Rodney Alexander; Waterman, Robert D.; Oostdyk, Rebecca Lynn; Ossenfort, John P.; Matthews, Bryan

    2010-01-01

    The automation of pre-launch diagnostics for launch vehicles offers three potential benefits: improving safety, reducing cost, and reducing launch delays. The Ares I-X Ground Diagnostic Prototype demonstrated anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage Thrust Vector Control and for the associated ground hydraulics while the vehicle was in the Vehicle Assembly Building at Kennedy Space Center (KSC) and while it was on the launch pad. The prototype combines three existing tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool from Qualtech Systems Inc. for fault isolation and diagnostics. The second tool, SHINE (Spacecraft Health Inference Engine), is a rule-based expert system that was developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification, and used the outputs of SHINE as inputs to TEAMS. The third tool, IMS (Inductive Monitoring System), is an anomaly detection tool that was developed at NASA Ames Research Center. The three tools were integrated and deployed to KSC, where they were interfaced with live data. This paper describes how the prototype performed during the period of time before the launch, including accuracy and computer resource usage. The paper concludes with some of the lessons that we learned from the experience of developing and deploying the prototype.

  8. Perceptions of Women's Teams Coaches Regarding Gender Equity and Title IX Compliance in Community Colleges

    ERIC Educational Resources Information Center

    Kenney, Cynthia A.

    2013-01-01

    Title IX was enacted over 40 years ago, and although there have been marked increases in the number of girls and women participating in athletics at every level, gender equity in athletics continues to be a concern. This is especially evident at the community college level. Title IX requires equity in the areas of opportunities for participation,…

  9. Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators.

    PubMed

    Wang, Xiaoshuang; Yang, Liu; Yang, Li; Xing, Faping; Yang, Hua; Qin, Liyue; Lan, Yunyi; Wu, Hui; Zhang, Beibei; Shi, Hailian; Lu, Cheng; Huang, Fei; Wu, Xiaojun; Wang, Zhengtao

    2017-12-01

    Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo. GP IX significantly reduced the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) at either protein or mRNA level in glial cell line C6 cells stimulated by lipopolysaccharide (LPS)/TNF-α combination. It also alleviated the astrogliosis and decreased the production of inflammatory mediators in brain cortex of LPS-treated mice. Further study disclosed that GP IX inhibited nuclear translocation of nuclear factor kappa B (NFκB) and reduced its transcriptional activity. Meanwhile, GP IX significantly attenuated the phosphorylation of NFκB, inhibitor of kappa B (IκB), Akt, and p38 mitogen-activated protein kinase (MAPK) under inflammatory conditions both in vitro and in vivo. These findings indicated that GP IX might suppress reactive astrogliosis by suppressing Akt/p38 MAPK/NFκB signaling pathways. And GP IX might be a promising drug candidate or prodrug for the therapy of neuroinflammatory disorders characterized with reactive astrogliosis.

  10. The Zinc Transporter Zip5 (Slc39a5) Regulates Intestinal Zinc Excretion and Protects the Pancreas against Zinc Toxicity

    PubMed Central

    Geiser, Jim; De Lisle, Robert C.; Andrews, Glen K.

    2013-01-01

    Background ZIP5 localizes to the baso-lateral membranes of intestinal enterocytes and pancreatic acinar cells and is internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. These cell-types are thought to control zinc excretion from the body. The baso-lateral localization and zinc-regulation of ZIP5 in these cells are unique among the 14 members of the Slc39a family and suggest that ZIP5 plays a role in zinc excretion. Methods/Principal Findings We created mice with floxed Zip5 genes and deleted this gene in the entire mouse or specifically in enterocytes or acinar cells and then examined the effects on zinc homeostasis. We found that ZIP5 is not essential for growth and viability but total knockout of ZIP5 led to increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of-function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally, loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation of 67zinc. Retention of pancreatic 67zinc was impaired in these mice but the absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and exacerbated the formation of large cytoplasmic vacuoles containing secretory protein in acinar cells. Conclusions These studies demonstrate that ZIP5 participates in the control of zinc excretion in mice. Specifically, they reveal a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in acinar cells to protect against zinc-induced acute pancreatitis and attenuate the process of zymophagy. This suggests that it may play a role in autophagy. PMID:24303081

  11. Ares I-X Best Estimated Trajectory Analysis and Results

    NASA Technical Reports Server (NTRS)

    Karlgaard, Christopher D.; Beck, Roger E.; Starr, Brett R.; Derry, Stephen D.; Brandon, Jay; Olds, Aaron D.

    2011-01-01

    The Ares I-X trajectory reconstruction produced best estimated trajectories of the flight test vehicle ascent through stage separation, and of the first and upper stage entries after separation. The trajectory reconstruction process combines on-board, ground-based, and atmospheric measurements to produce the trajectory estimates. The Ares I-X vehicle had a number of on-board and ground based sensors that were available, including inertial measurement units, radar, air-data, and weather balloons. However, due to problems with calibrations and/or data, not all of the sensor data were used. The trajectory estimate was generated using an Iterative Extended Kalman Filter algorithm, which is an industry standard processing algorithm for filtering and estimation applications. This paper describes the methodology and results of the trajectory reconstruction process, including flight data preprocessing and input uncertainties, trajectory estimation algorithms, output transformations, and comparisons with preflight predictions.

  12. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    PubMed

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  13. Absence of collagen IX accelerates hypertrophic differentiation in the embryonic mouse spine through a disturbance of the Ihh-PTHrP feedback loop.

    PubMed

    Kamper, Matthias; Paulsson, Mats; Zaucke, Frank

    2017-02-01

    Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice. Histological staining was used to show tissue morphology at different time points. Localization of extracellular matrix proteins as well as components of signaling pathways were analyzed by immunohistochemistry. Developing vertebral bodies of Col IX -/- mice were smaller and already appeared more compact at E12.5. At E15.5, vertebral bodies of Col IX -/- mice revealed an increased number of hypertrophic chondrocytes as well as enhanced staining for the terminal differentiation markers alkaline phosphatase and collagen X. This correlates with an imbalance in the Ihh-PTHrP signaling pathway at this time point, reflected by an increase of Ihh and a concomitant decrease of PTHrP expression. An accelerated hypertrophic differentiation caused by a disturbed Ihh-PTHrP signaling pathway may lead to a higher bone mineral density in the vertebral bodies of newborn Col IX -/- mice and, as a result, to the early onset of disc degeneration.

  14. Avidin-Based Targeting and Purification of a Protein IX-Modified, Metabolically Biotinylated Adenoviral Vector

    PubMed Central

    Campos, Samuel K.; Parrott, M. Brandon; Barry, Michael A.

    2014-01-01

    While genetic modification of adenoviral vectors can produce vectors with modified tropism, incorporation of targeting peptides/proteins into the structural context of the virion can also result in destruction of ligand targeting or virion integrity. To combat this problem, we have developed a versatile targeting system using metabolically biotinylated adenoviral vectors bearing biotinylated fiber proteins. These vectors have been demonstrated to be useful as a platform for avidin-based ligand screening and vector targeting by conjugating biotinylated ligands to the virus using high-affinity tetrameric avidin (Kd = 10−15 M). The biotinylated vector could also be purified by biotin-reversible binding on monomeric avidin (Kd = 10−7 M). In this report, a second metabolically biotinylated adenovirus vector, Ad-IX-BAP, has been engineered by fusing a biotin acceptor peptide (BAP) to the C-terminus of the adenovirus pIX protein. This biotinylated vector displays twice as many biotins and was markedly superior for single-step affinity purification on monomeric avidin resin. However, unlike the fiber-biotinylated vector, Ad-IX-BAP failed to retarget to cells with biotinylated antibodies including anti-CD71 against the transferrin receptor. In contrast, Ad-IX-BAP was retargeted if transferrin, the cognate ligand for CD71, was used as a ligand rather than the anti-CD71. This work demonstrates the utility of metabolic biotinylation as a molecular screening tool to assess the utility of different viral capsid proteins for ligand display and the biology and compatibility of different ligands and receptors for vector targeting applications. These results also demonstrate the utility of the pIX-biotinylated vector as a platform for gentle single-step affinity purification of adenoviral vectors. PMID:15194061

  15. Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs.

    PubMed

    Li, Guangqi; Chen, Sirui; Duan, Zhongyi; Qu, Lujiang; Xu, Guiyun; Yang, Ning

    2013-12-01

    Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland.

  16. 29. Photocopy of 1921 photograph. Glass Negative Box IX, Tower ...

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

    29. Photocopy of 1921 photograph. Glass Negative Box IX, Tower Grove, Missouri Botanical Garden. ITALIAN GARDEN AND NEW PALM HOUSE (DEMOLISHED), LOOKING NORTHEAST - Missouri Botanical Garden, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

  17. Zinc pharmacokinetic parameters in the determination of body zinc status in children.

    PubMed

    Vale, S H L; Leite, L D; Alves, C X; Dantas, M M G; Costa, J B S; Marchini, J S; França, M C; Brandão-Neto, J

    2014-02-01

    Serum or tissue zinc concentrations are often used to assess body zinc status. However, all of these methods are relatively inaccurate. Thus, we investigated three different kinetic methods for the determination of zinc clearance to establish which of these could detect small changes in the body zinc status of children. Forty apparently healthy children were studied. Renal handling of zinc was investigated during intravenous zinc administration (0.06537 mg Zn/kg of body weight), both before and after oral zinc supplementation (5 mg Zn/day for 3 months). Three kinetic methods were used to determine zinc clearance: CZn-Formula A and CZn-Formula B were both used to calculate systemic clearance; the first is a general formula and the second is used for the specific analysis of a single-compartment model; CZn-Formula C is widely used in medical practices to analyze kinetic routine. Basal serum zinc values, which were within the reference range for healthy children, increased significantly after oral zinc supplementation. The three formulas used gave different results for zinc clearance both before and after oral zinc supplementation. CZn-Formula B showed a positive correlation with basal serum zinc concentration after oral supplementation (R2=0.1172, P=0.0306). In addition, CZn-Formula B (P=0.0002) was more effective than CZn-Formula A (P=0.6028) and CZn-Formula C (P=0.0732) in detecting small variations in body zinc status. All three of the formulas used are suitable for studying zinc kinetics; however, CZn-Formula B is particularly effective at detecting small changes in body zinc status in healthy children.

  18. Morphology control of zinc regeneration for zinc-air fuel cell and battery

    NASA Astrophysics Data System (ADS)

    Wang, Keliang; Pei, Pucheng; Ma, Ze; Xu, Huachi; Li, Pengcheng; Wang, Xizhong

    2014-12-01

    Morphology control is crucial both for zinc-air batteries and for zinc-air fuel cells during zinc regeneration. Zinc dendrite should be avoided in zinc-air batteries and zinc pellets are yearned to be formed for zinc-air fuel cells. This paper is mainly to analyze the mechanism of shape change and to control the zinc morphology during charge. A numerical three-dimensional model for zinc regeneration is established with COMSOL software on the basis of ionic transport theory and electrode reaction electrochemistry, and some experiments of zinc regeneration are carried out. The deposition process is qualitatively analyzed by the kinetics Monte Carlo method to study the morphological change from the electrocrystallization point of view. Morphological evolution of deposited zinc under different conditions of direct currents and pulse currents is also investigated by simulation. The simulation shows that parametric variables of the flowing electrolyte, the surface roughness and the structure of the electrode, the charging current and mode affect morphological evolution. The uniform morphology of deposited zinc is attained at low current, pulsating current or hydrodynamic electrolyte, and granular morphology is obtained by means of an electrode of discrete columnar structure in combination with high current and flowing electrolyte.

  19. Almost As Fairly: The First Year of Title IX Implementation in Six Southern States. A Report.

    ERIC Educational Resources Information Center

    American Friends Service Committee, Columbia, SC. Southeastern Public Education Program.

    Volunteers from community organizations in six southern states monitored 21 school districts to find their districts' initial answer to Title IX, federal legislation barring sex discrimination. The actual monitoring of the 21 districts was completed in the late spring of 1976, with data covering the first year of Title IX implementation. The…

  20. Zinc and Autophagy

    PubMed Central

    Liuzzi, Juan P.; Guo, Liang; Yoo, Changwon; Stewart, Tiffanie S

    2014-01-01

    Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated.Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria.Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake. PMID:25012760

  1. A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc.

    PubMed

    Wastney, Meryl E; McDonald, Christine M; King, Janet C

    2018-05-01

    Zinc deficiency limits infant growth and increases susceptibility to infections, which further compromises growth. Zinc supplementation improves the growth of zinc-deficient stunted infants, but the amount, frequency, and duration of zinc supplementation required to restore growth in an individual child is unknown. A dynamic model of zinc metabolism that predicts changes in weight and length of zinc-deficient, stunted infants with dietary zinc would be useful to define effective zinc supplementation regimens. The aims of this study were to develop a dynamic model for zinc metabolism in stunted, zinc-deficient infants and to use that model to predict the growth response when those infants are given zinc supplements. A model of zinc metabolism was developed using data on zinc kinetics, tissue zinc, and growth requirements for healthy 9-mo-old infants. The kinetic model was converted to a dynamic model by replacing the rate constants for zinc absorption and excretion with functions for these processes that change with zinc intake. Predictions of the dynamic model, parameterized for zinc-deficient, stunted infants, were compared with the results of 5 published zinc intervention trials. The model was then used to predict the results for zinc supplementation regimes that varied in the amount, frequency, and duration of zinc dosing. Model predictions agreed with published changes in plasma zinc after zinc supplementation. Predictions of weight and length agreed with 2 studies, but overpredicted values from a third study in which other nutrient deficiencies may have been growth limiting; the model predicted that zinc absorption was impaired in that study. The model suggests that frequent, smaller doses (5-10 mg Zn/d) are more effective for increasing growth in stunted, zinc-deficient 9-mo-old infants than are larger, less-frequent doses. The dose amount affects the duration of dosing necessary to restore and maintain plasma zinc concentration and growth.

  2. Secondary Athletic Administrators' Perceptions of Title IX Policy Changes

    ERIC Educational Resources Information Center

    Dahl, Gabriel Grawe

    2012-01-01

    The purpose of this study was to investigate North Dakota's Normal Competitive Region (NDNCR) high school athletic administrators' perceptions of 2010 Title IX policy changes respective to their athletic programs. Quantitative and qualitative data were collected to investigate the perceptions. Quantitatively, perception data were gathered from a…

  3. Early events in photodynamic therapy: chemical and physical changes in a POPC:cholesterol bilayer due to hematoporphyrin IX-mediated photosensitization.

    PubMed

    Santos, António; Rodrigues, António M; Sobral, Abílio J F N; Monsanto, Paula V; Vaz, Winchil L C; Moreno, Maria João

    2009-01-01

    We studied the interaction of hematoporphyrin IX (HpIX) with bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) containing cholesterol at a molar fraction between 0 and 0.5. The membrane-associated fraction of HpIX decreases significantly over a period of hours, for porphyrin concentrations in the aqueous phase above 50 nM. This was attributed to self-aggregation of HpIX and was well described by a dimerization process. A model was developed to correct for aggregation and obtain the true partition coefficient which is dependent on the molar fraction of cholesterol with a maximum at 20 mol%. The chemical and physical effects on the lipid bilayer upon irradiation of HpIX were studied for lipid bilayers with POPC:Chol 1:1. Exposure of these bilayers to visible light in the presence of HpIX leads to several cholesterol oxidation products that were identified using GC-MS. A dramatic increase in the membrane leakiness was also observed, even for short irradiation times and small light intensities, as evaluated from the rate of pH equilibration and dithionite permeability. The relevance of these results for the mechanism of photodynamic therapy is discussed.

  4. Production of zinc pellets

    DOEpatents

    Cooper, J.F.

    1996-11-26

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries. 6 figs.

  5. Production of zinc pellets

    DOEpatents

    Cooper, John F.

    1996-01-01

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries.

  6. Zinc Signals and Immunity.

    PubMed

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  7. Zinc Signals and Immunity

    PubMed Central

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-01-01

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as “zinc waves”, and late homeostatic zinc signals regarding prolonged changes in intracellular zinc. PMID:29064429

  8. Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".

    PubMed

    Maret, Wolfgang

    2017-10-31

    In the last decade, we witnessed discoveries that established Zn 2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca 2+ and Mg 2+ , Zn 2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca 2+ , redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.

  9. Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

    PubMed

    Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

    2018-03-05

    Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

  10. Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

    PubMed

    Kogan, Samuel; Sood, Aditya; Garnick, Mark S

    2017-04-01

    Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

  11. Counselor Education and Title IX: Current Perceptions and Questions

    ERIC Educational Resources Information Center

    Welfare, Laura E.; Wagstaff, Jennifer; Haynes, Jenna R.

    2017-01-01

    This national survey of counselor educator perceptions of the Title IX requirement to report student disclosures of gender-based discrimination revealed the need for greater clarity about faculty strategies for serving counseling program students while upholding the federal law. The authors describe the recent expansion of the requirements and…

  12. Zinc

    MedlinePlus

    ... Guidelines for Americans and the U.S. Department of Agriculture's MyPlate . Where can I find out more about ... on food sources of zinc: U.S. Department of Agriculture's (USDA’s) National Nutrient Database Nutrient List for zinc ( ...

  13. Big Men on Campus: Administrative Response to Title IX and the Development of Women's Sports in the Big Ten Conference, 1972-1982

    ERIC Educational Resources Information Center

    Ramsey, Jeffrey T.

    2014-01-01

    Signed into law in 1972, Title IX of the Education Amendments was designed to eliminate gender discrimination throughout the American educational system. Title IX applied to all educational programs at any level of schooling including admissions, financial aid, academic programs, and social organizations. However, Title IX has primarily been…

  14. Qualitative cosmology - Diagrammatic solutions for Bianchi type IX universes with expansion, rotation, and shear. II.

    NASA Technical Reports Server (NTRS)

    Ryan, M. P., Jr.

    1971-01-01

    The investigation of expanding, rotating, shearing Bianchi type IX universes is extended to the most general case possible. Use is made of the techniques of Arnowitt et al. (1962). It is shown that the conclusion reached by Arnowitt et al. regarding the small effect of rotation on the singularity of type IX universes is true in general. The superspace approach to the motion of the universe is discussed in an appendix.

  15. Hyperaccumulation of zinc by zinc-depleted Candida utilis grown in chemostat culture.

    PubMed

    Lawford, H G; Pik, J R; Lawford, G R; Williams, T; Kligerman, A

    1980-01-01

    The steady-state levels of zinc in Candida utilis yeast grown in continuous culture under conditions of zinc limitations are <1nmol Zn2+/mg dry weight of cells. Unlike carbon-limited cells, zinc-depleted cells from a zinc-limited chemostat possess the capacity to accumulate and store zinc at levels far in excess of the steady-state level of 4 nmol/mg dry biomass observed in carbon-limited chemostat cultures. Zinc uptake is energy-dependent and apparently undirectional since accumulated 65Zn neither exists from preloaded cells nor exchanges with cold Zn2+. The transport system exhibits a high affinity for Zn2+ (Km =.36micrM) with a Vmaxof 2.2 nmol per minute per milligram dry weight of cells. Growth during the period of the uptake assay is responsible for the apparent plateau level of 35 nmol Zn2+/mg dry weight of cells achieved after 20-30 min in the presence of 65Zn at pH 4.5 and 30 degrees C. Inhibition of growth during the uptake assay by cycloheximide results in a biphasic linear pattern of zinc accumulation where the cellular zinc is about 60 nmol/mg dry weight after 1 h. The enhanced level of accumulated zinc is not inhibtory to growth. Zinc-depleted C. utilis contains elevated amounts of polyphosphate and this anionic evidence does not allow discrimination between possible regulation of zinc homestasis either by inhibitions of zinc efflux through control of the membrane carrier or by control of the synthesis of a cytoplasmic zinc-sequestering macromolecule.

  16. Factor IX[sub Madrid 2]: A deletion/insertion in Facotr IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site

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

    Solera, J.; Magallon, M.; Martin-Villar, J.

    1992-02-01

    DNA from a patient with severe hemophilia B was evaluated by RFLP analysis, producing results which suggested the existence of a partial deletion within the factor IX gene. The deletion was further localized and characterized by PCR amplification and sequencing. The altered allele has a 4,442-bp deletion which removes both the donor splice site located at the 5[prime] end of intron d and the two last coding nucleotides located at the 3[prime] end of exon IV in the normal factor IX gene; this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends ofmore » the deleted DNA fragment.« less

  17. A Clash of Titans: College Football v. Title IX.

    ERIC Educational Resources Information Center

    Pieronek, Catherine

    1994-01-01

    Title IX of the Educational Amendments of 1972, Civil Rights Act of 1971, designed to ensure equal educational opportunity for men and women, is reviewed as it pertains to college athletics. Related litigation and National Collegiate Athletic Association efforts to promote compliance are examined, an argument for excluding revenue-producing sports…

  18. Update on zinc biology.

    PubMed

    Solomons, Noel W

    2013-01-01

    Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation. Copyright © 2013 S. Karger AG, Basel.

  19. Zinc at glutamatergic synapses.

    PubMed

    Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

    2009-01-12

    It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

  20. Ares I-X Separation and Reentry Trajectory Analyses

    NASA Technical Reports Server (NTRS)

    Tartabini, Paul V.; Starr, Brett R.

    2011-01-01

    The Ares I-X Flight Test Vehicle was launched on October 28, 2009 and was the first and only test flight of NASA s two-stage Ares I launch vehicle design. The launch was successful and the flight test met all of its primary and secondary objectives. This paper discusses the stage separation and reentry trajectory analysis that was performed in support of the Ares I-X test flight. Pre-flight analyses were conducted to assess the risk of stage recontact during separation, to evaluate the first stage flight dynamics during reentry, and to define the range safety impact ellipses of both stages. The results of these pre-flight analyses were compared with available flight data. On-board video taken during flight showed that the flight test vehicle successfully separated without any recontact. Reconstructed trajectory data also showed that first stage flight dynamics were well characterized by pre-flight Monte Carlo results. In addition, comparisons with flight data indicated that the complex interference aerodynamic models employed in the reentry simulation were effective in capturing the flight dynamics during separation. Finally, the splash-down locations of both stages were well within predicted impact ellipses.

  1. Young Stellar Populations in MYStIX Star-forming Regions: Candidate Protostars

    NASA Astrophysics Data System (ADS)

    Romine, Gregory; Feigelson, Eric D.; Getman, Konstantin V.; Kuhn, Michael A.; Povich, Matthew S.

    2016-12-01

    The Massive Young Star-Forming Complex in Infrared and X-ray (MYStIX) project provides a new census on stellar members of massive star-forming regions within 4 kpc. Here the MYStIX Infrared Excess catalog and Chandra-based X-ray photometric catalogs are mined to obtain high-quality samples of Class I protostars using criteria designed to reduce extragalactic and Galactic field star contamination. A total of 1109 MYStIX Candidate Protostars (MCPs) are found in 14 star-forming regions. Most are selected from protoplanetary disk infrared excess emission, but 20% are found from their ultrahard X-ray spectra from heavily absorbed magnetospheric flare emission. Two-thirds of the MCP sample is newly reported here. The resulting samples are strongly spatially associated with molecular cores and filaments on Herschel far-infrared maps. This spatial agreement and other evidence indicate that the MCP sample has high reliability with relatively few “false positives” from contaminating populations. But the limited sensitivity and sparse overlap among the infrared and X-ray subsamples indicate that the sample is very incomplete with many “false negatives.” Maps, tables, and source descriptions are provided to guide further study of star formation in these regions. In particular, the nature of ultrahard X-ray protostellar candidates without known infrared counterparts needs to be elucidated.

  2. YOUNG STELLAR POPULATIONS IN MYStIX STAR-FORMING REGIONS: CANDIDATE PROTOSTARS

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

    Romine, Gregory; Feigelson, Eric D.; Getman, Konstantin V.

    The Massive Young Star-Forming Complex in Infrared and X-ray (MYStIX) project provides a new census on stellar members of massive star-forming regions within 4 kpc. Here the MYStIX Infrared Excess catalog and Chandra -based X-ray photometric catalogs are mined to obtain high-quality samples of Class I protostars using criteria designed to reduce extragalactic and Galactic field star contamination. A total of 1109 MYStIX Candidate Protostars (MCPs) are found in 14 star-forming regions. Most are selected from protoplanetary disk infrared excess emission, but 20% are found from their ultrahard X-ray spectra from heavily absorbed magnetospheric flare emission. Two-thirds of the MCP sample ismore » newly reported here. The resulting samples are strongly spatially associated with molecular cores and filaments on Herschel far-infrared maps. This spatial agreement and other evidence indicate that the MCP sample has high reliability with relatively few “false positives” from contaminating populations. But the limited sensitivity and sparse overlap among the infrared and X-ray subsamples indicate that the sample is very incomplete with many “false negatives.” Maps, tables, and source descriptions are provided to guide further study of star formation in these regions. In particular, the nature of ultrahard X-ray protostellar candidates without known infrared counterparts needs to be elucidated.« less

  3. The scorpion toxin Bot IX is a potent member of the α-like family and has a unique N-terminal sequence extension.

    PubMed

    Martin-Eauclaire, Marie-France; Salvatierra, Juan; Bosmans, Frank; Bougis, Pierre E

    2016-09-01

    We report the detailed chemical, immunological and pharmacological characterization of the α-toxin Bot IX from the Moroccan scorpion Buthus occitanus tunetanus venom. Bot IX, which consists of 70 amino acids, is a highly atypical toxin. It carries a unique N-terminal sequence extension and is highly lethal in mice. Voltage clamp recordings on oocytes expressing rat Nav1.2 or insect BgNav1 reveal that, similar to other α-like toxins, Bot IX inhibits fast inactivation of both variants. Moreover, Bot IX belongs to the same structural/immunological group as the α-like toxin Bot I. Remarkably, radioiodinated Bot IX competes efficiently with the classical α-toxin AaH II from Androctonus australis, and displays one of the highest affinities for Nav channels. © 2016 Federation of European Biochemical Societies.

  4. Zinc and Zinc Transporters: Novel Regulators of Ventricular Myocardial Development.

    PubMed

    Lin, Wen; Li, Deqiang

    2018-06-01

    Ventricular myocardial development is a well-orchestrated process involving different cardiac structures, multiple signal pathways, and myriad proteins. Dysregulation of this important developmental event can result in cardiomyopathies, such as left ventricle non-compaction, which affect the pediatric population and the adults. Human and mouse studies have shed light upon the etiology of some cardiomyopathy cases and highlighted the contribution of both genetic and environmental factors. However, the regulation of ventricular myocardial development remains incompletely understood. Zinc is an essential trace metal with structural, enzymatic, and signaling function. Perturbation of zinc homeostasis has resulted in developmental and physiological defects including cardiomyopathy. In this review, we summarize several mechanisms by which zinc and zinc transporters can impact the regulation of ventricular myocardial development. Based on our review, we propose that zinc deficiency and mutations of zinc transporters may underlie some cardiomyopathy cases especially those involving ventricular myocardial development defects.

  5. Expanding the versatility of phage display II: improved affinity selection of folded domains on protein VII and IX of the filamentous phage.

    PubMed

    Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

    2011-02-24

    Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before.

  6. Expanding the Versatility of Phage Display II: Improved Affinity Selection of Folded Domains on Protein VII and IX of the Filamentous Phage

    PubMed Central

    Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

    2011-01-01

    Background Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Methodology/Principal Findings Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Conclusions/Significance Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before. PMID:21390283

  7. Growth stimulation of Porphyromonas endodontalis by hemoglobin and protoporphyrin IX.

    PubMed

    Zerr, M A; Cox, C D; Johnson, W T; Drake, D R

    2000-12-01

    Porphyromonas endodontalis, like other Porphyromonas species, has a complex set of nutritional requirements. In addition to being an obligate anaerobe, the bacterium must be grown in a complex medium consisting of amino acids, reducing agents and heme compounds. P. endodontalis accumulates high concentrations of heme pigments to the extent that colonies appear black on blood agar. This accumulation of heme and the need for these compounds has been characterized as iron requirements by these species. However, in our studies, P. endodontalis demonstrated growth dependence on hemoglobin or protoporphyrin IX but not on free iron. Iron added to other heme compounds actually decreased growth stimulation by porphyrin-containing compounds. P. endodontalis actively transported free iron, but this process did not appear to be critical for growth. The maximum stimulation of growth by protoporphyrin IX, under conditions of iron deprivation, suggests that P. endodontalis requires the porphyrin moiety as a growth factor.

  8. Motives and periods in Bianchi IX gravity models

    NASA Astrophysics Data System (ADS)

    Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

    2018-05-01

    We show that, when considering the anisotropic scaling factors and their derivatives as affine variables, the coefficients of the heat-kernel expansion of the Dirac-Laplacian on SU(2) Bianchi IX metrics are algebro-geometric periods of motives of complements in affine spaces of unions of quadrics and hyperplanes. We show that the motives are mixed Tate and we provide an explicit computation of their Grothendieck classes.

  9. Title IX, girls' sports participation, and adult female physical activity and weight.

    PubMed

    Kaestner, Robert; Xin Xu

    2010-02-01

    Arguably, the most important school-based intervention to increase physical activity was Title IX of the Education Amendments of 1972, which led to a 600% increase in girls' sports participation between 1972 and 1978. We studied the effect of this increase in sports participation and athletic opportunities while young on the physical activity and weight of adult women some 20-25 years later. Our results indicate that adult women who were affected by Title IX and had greater opportunity to participate in athletics while young had lower body mass index (BMI) and lower rates of obesity and reported being more physically active than women who were not afforded these opportunities. However, effect sizes were quite modest.

  10. Immunosuppressive effects of factor IX products: an in vitro study.

    PubMed

    Grosset, A B; McGregor, J R; Samlowski, W E; Rodgers, G M

    1999-11-01

    The effects of a recombinant factor IX product (BeneFix), and of five plasma-derived factor IX products, AlphaNine, Immunine, Konyne, Mononine and Replinine on in vitro peripheral blood mononuclear cell (PBMC) immune function were compared in a blinded study. We assessed the effects of these products on Con-A-induced lymphocyte proliferation and interleukin-2 and interleukin-10 secretion, expression of lymphocyte activation markers, and nitric oxide secretion by stimulated mouse peritoneal macrophages. At 1 mL-1 for 48 h, Konyne reduced Con-A-induced mitogenesis by 50% (P < 0.05); AlphaNine, Mononine and BeneFix had no effect. At 10 IU mL-1, Con-A-induced mi- togenesis was at control levels with Mononine and BeneFix, but was reduced to <15% (P < 0.05) with each of the other products. IL-2 and IL-10 secretion by Con-A-stimulated lymphocytes was also markedly depressed by all the products tested except Mononine and BeneFix. Dialysis of these products did not substantially affect these results. Flow cytometric analysis of lymphocyte activation markers following Con-A stimulation showed that Konyne also decreased IL-2 receptor alpha and beta chain (CD25 and CD122) induction on PBMC. Konyne also inhibited nitric oxide secretion to levels <18% of controls. These results indicate that certain factor IX products, including some of purported higher purity, substantially depress in vitro immune function. The importance of these findings to in vivo immune function in haemophilia B patients remains to be established.

  11. Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX.

    PubMed

    Poulin, Kathy L; Lanthier, Robert M; Smith, Adam C; Christou, Carin; Risco Quiroz, Milagros; Powell, Karen L; O'Meara, Ryan W; Kothary, Rashmi; Lorimer, Ian A; Parks, Robin J

    2010-10-01

    Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting. We show that scFv can be displayed on the capsid through genetic fusion to native pIX but that these molecules fail to retarget the virus, due to improper folding of the scFv. Redirecting expression of the fusion protein to the endoplasmic reticulum (ER) results in correct folding of the scFv and allows it to recognize its epitope; however, ER-targeted pIX-scFv was incorporated into the Ad capsid at a very low level which was not sufficient to retarget virus infection. In contrast, a pIX-sdAb construct was efficiently incorporated into the Ad capsid and enhanced virus infection of cells expressing the targeted receptor. Taken together, our data indicate that pIX is an effective platform for presentation of large targeting polypeptides on the surface of the virus capsid, but the nature of the ligand can significantly affect its association with virions.

  12. Ares I-X Flight Test Philosophy

    NASA Technical Reports Server (NTRS)

    Davis, S. R.; Tuma, M. L.; Heitzman, K.

    2007-01-01

    In response to the Vision for Space Exploration, the National Aeronautics and Space Administration (NASA) has defined a new space exploration architecture to return humans to the Moon and prepare for human exploration of Mars. One of the first new developments will be the Ares I Crew Launch Vehicle (CLV), which will carry the Orion Crew Exploration Vehicle (CEV), into Low Earth Orbit (LEO) to support International Space Station (ISS) missions and, later, support lunar missions. As part of Ares I development, NASA will perform a series of Ares I flight tests. The tests will provide data that will inform the engineering and design process and verify the flight hardware and software. The data gained from the flight tests will be used to certify the new Ares/Orion vehicle for human space flight. The primary objectives of this first flight test (Ares I-X) are the following: Demonstrate control of a dynamically similar integrated Ares CLV/Orion CEV using Ares CLV ascent control algorithms; Perform an in-flight separation/staging event between an Ares I-similar First Stage and a representative Upper Stage; Demonstrate assembly and recovery of a new Ares CLV-like First Stage element at Kennedy Space Center (KSC); Demonstrate First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics and parachute performance; and Characterize the magnitude of the integrated vehicle roll torque throughout the First Stage (powered) flight. This paper will provide an overview of the Ares I-X flight test process and details of the individual flight tests.

  13. Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence.

    PubMed

    Liu, Wenwen; Xie, Liangxiao; Liu, Hongshuang; Xu, Shichao; Hu, Bingcheng; Cao, Wei

    2013-01-01

    A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10(-8) to 1.0 × 10(-5) g/mL. Detection limit (3σ) was estimated to be 3.5 × 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Ares I-X Upper Stage Simulator Residual Stress Analysis

    NASA Technical Reports Server (NTRS)

    Raju, Ivatury S.; Brust, Frederick W.; Phillips, Dawn R.; Cheston, Derrick

    2008-01-01

    The structural analyses described in the present report were performed in support of the NASA Engineering and Safety Center (NESC) Critical Initial Flaw Size (CIFS) assessment for the Ares I-X Upper Stage Simulator (USS) common shell segment. An independent assessment was conducted to determine the critical initial flaw size (CIFS) for the flange-to-skin weld in the Ares I-X Upper Stage Simulator (USS). The Ares system of space launch vehicles is the US National Aeronautics and Space Administration s plan for replacement of the aging space shuttle. The new Ares space launch system is somewhat of a combination of the space shuttle system and the Saturn launch vehicles used prior to the shuttle. Here, a series of weld analyses are performed to determine the residual stresses in a critical region of the USS. Weld residual stresses both increase constraint and mean stress thereby having an important effect on fatigue and fracture life. The results of this effort served as one of the critical load inputs required to perform a CIFS assessment of the same segment.

  15. Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life12

    PubMed Central

    Maret, Wolfgang

    2013-01-01

    The nutritional essentiality of zinc for the growth of living organisms had been recognized long before zinc biochemistry began with the discovery of zinc in carbonic anhydrase in 1939. Painstaking analytical work then demonstrated the presence of zinc as a catalytic and structural cofactor in a few hundred enzymes. In the 1980s, the field again gained momentum with the new principle of “zinc finger” proteins, in which zinc has structural functions in domains that interact with other biomolecules. Advances in structural biology and a rapid increase in the availability of gene/protein databases now made it possible to predict zinc-binding sites from metal-binding motifs detected in sequences. This procedure resulted in the definition of zinc proteomes and the remarkable estimate that the human genome encodes ∼3000 zinc proteins. More recent developments focus on the regulatory functions of zinc(II) ions in intra- and intercellular information transfer and have tantalizing implications for yet additional functions of zinc in signal transduction and cellular control. At least three dozen proteins homeostatically control the vesicular storage and subcellular distribution of zinc and the concentrations of zinc(II) ions. Novel principles emerge from quantitative investigations on how strongly zinc interacts with proteins and how it is buffered to control the remarkably low cellular and subcellular concentrations of free zinc(II) ions. It is fair to conclude that the impact of zinc for health and disease will be at least as far-reaching as that of iron. PMID:23319127

  16. Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats.

    PubMed

    Kuldeep, Anjana; Nair, Neena; Bedwal, Ranveer Singh

    2017-06-01

    The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30-40 days of age, pre-pubertal period) of 40-50 g body weight were divided into the following: the ZC (zinc control) group-fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group-fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group-received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

  17. Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

    PubMed Central

    Nathwani, A.C.; Reiss, U.M.; Tuddenham, E.G.D.; Rosales, C.; Chowdary, P.; McIntosh, J.; Della Peruta, M.; Lheriteau, E.; Patel, N.; Raj, D.; Riddell, A.; Pie, J.; Rangarajan, S.; Bevan, D.; Recht, M.; Shen, Y.-M.; Halka, K.G.; Basner-Tschakarjan, E.; Mingozzi, F.; High, K.A.; Allay, J.; Kay, M.A.; Ng, C.Y.C.; Zhou, J.; Cancio, M.; Morton, C.L.; Gray, J.T.; Srivastava, D.; Nienhuis, A.W.; Davidoff, A.M.

    2014-01-01

    BACKGROUND In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose–response relationship, and the level of persistent or late toxicity. METHODS We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×1012 vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; Clinical

  18. Contribution of Zinc Solubilizing Bacteria in Growth Promotion and Zinc Content of Wheat.

    PubMed

    Kamran, Sana; Shahid, Izzah; Baig, Deeba N; Rizwan, Muhammad; Malik, Kauser A; Mehnaz, Samina

    2017-01-01

    Zinc is an imperative micronutrient required for optimum plant growth. Zinc solubilizing bacteria are potential alternatives for zinc supplementation and convert applied inorganic zinc to available forms. This study was conducted to screen zinc solubilizing rhizobacteria isolated from wheat and sugarcane, and to analyze their effect on wheat growth and development. Fourteen exo-polysaccharides producing bacterial isolates of wheat were identified and characterized biochemically as well as on the basis of 16S rRNA gene sequences. Along these, 10 identified sugarcane isolates were also screened for zinc solubilizing ability on five different insoluble zinc sources. Out of 24, five strains, i.e., EPS 1 ( Pseudomonas fragi) , EPS 6 ( Pantoea dispersa) , EPS 13 ( Pantoea agglomerans) , PBS 2 ( E. cloacae) and LHRW1 ( Rhizobium sp.) were selected (based on their zinc solubilizing and PGP activities) for pot scale plant experiments. ZnCO 3 was used as zinc source and wheat seedlings were inoculated with these five strains, individually, to assess their effect on plant growth and development. The effect on plants was analyzed based on growth parameters and quantifying zinc content of shoot, root and grains using atomic absorption spectroscopy. Plant experiment was performed in two sets. For first set of plant experiments (harvested after 1 month), maximum shoot and root dry weights and shoot lengths were noted for the plants inoculated with Rhizobium sp. (LHRW1) while E. cloacae (PBS 2) increased both shoot and root lengths. Highest zinc content was found in shoots of E. cloacae (PBS 2) and in roots of P. agglomerans (EPS 13) followed by zinc supplemented control. For second set of plant experiment, when plants were harvested after three months, Pantoea dispersa (EPS 6), P. agglomerans (EPS 13) and E. cloacae (PBS 2) significantly increased shoot dry weights. However, significant increase in root dry weights and maximum zinc content was recorded for Pseudomonas fragi (EPS

  19. Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

    PubMed

    Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

    2017-03-01

    Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

  20. Zinc

    USDA-ARS?s Scientific Manuscript database

    Zinc was recognized as an essential trace metal for humans during the studies of Iranian adolescent dwarfs in the early 1960s. Zinc metal existing as Zn2+ is a strong electron acceptor in biological systems without risks of oxidant damage to cells. Zn2+ functions in the structure of proteins and is ...

  1. Zinc and Chlamydia trachomatis

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

    Sugarman, B.; Epps, L.R.

    1985-07-01

    Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 x 10/sup -4/ M) in the inoculation media compared with standard Chlamydia cultivation media (8 x 10/sup -6/ M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remainedmore » constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10/sup -4/ M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptibility to Chamydia trachomatis infections.« less

  2. Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

    PubMed

    Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

    1995-01-01

    The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1

  3. Association between Maternal Zinc Status, Dietary Zinc Intake and Pregnancy Complications: A Systematic Review

    PubMed Central

    Wilson, Rebecca L.; Grieger, Jessica A.; Bianco-Miotto, Tina; Roberts, Claire T.

    2016-01-01

    Adequate zinc stores in the body are extremely important during periods of accelerated growth. However, zinc deficiency is common in developing countries and low maternal circulating zinc concentrations have previously been associated with pregnancy complications. We reviewed current literature assessing circulating zinc and dietary zinc intake during pregnancy and the associations with preeclampsia (PE); spontaneous preterm birth (sPTB); low birthweight (LBW); and gestational diabetes (GDM). Searches of MEDLINE; CINAHL and Scopus databases identified 639 articles and 64 studies were reviewed. In 10 out of 16 studies a difference was reported with respect to circulating zinc between women who gave birth to a LBW infant (≤2500 g) and those who gave birth to an infant of adequate weight (>2500 g), particularly in populations where inadequate zinc intake is prevalent. In 16 of our 33 studies an association was found between hypertensive disorders of pregnancy and circulating zinc; particularly in women with severe PE (blood pressure ≥160/110 mmHg). No association between maternal zinc status and sPTB or GDM was seen; however; direct comparisons between the studies was difficult. Furthermore; only a small number of studies were based on women from populations where there is a high risk of zinc deficiency. Therefore; the link between maternal zinc status and pregnancy success in these populations cannot be established. Future studies should focus on those vulnerable to zinc deficiency and include dietary zinc intake as a measure of zinc status. PMID:27754451

  4. Knock-out of the magnesium protoporphyrin IX methyltransferase gene in Arabidopsis. Effects on chloroplast development and on chloroplast-to-nucleus signaling

    PubMed Central

    Pontier, Dominique; Albrieux, Catherine; Joyard, Jacques; Lagrange, Thierry; Block, Maryse

    2007-01-01

    Protoporphyrin IX is the last common intermediate between the haem and chlorophyll biosynthesis pathways. The addition of Mg directs this molecule toward chlorophyll biosynthesis. The first step downstream from the branchpoint is catalyzed by the Mg chelatase and is a highly regulated process. The corresponding product, Mg protoporphyrin IX, has been proposed to play an important role as a signaling molecule implicated in plastid-to-nucleus communication. In order to get more information on the chlorophyll biosynthesis pathway and on Mg protoporphyrin IX derivative functions, we have identified an Mg protoporphyrin IX methyltransferase (CHLM) knock-out mutant in Arabidopsis in which the mutation induces a blockage downstream from Mg protoporphyrin IX and an accumulation of this chlorophyll biosynthesis intermediate. Our results demonstrate that the CHLM gene is essential for the formation of chlorophyll and subsequently for the formation of photosystems I and II and cyt b6f complexes. Analysis of gene expression in the chlm mutant provides an independent indication that Mg protoporphyrin IX is a negative effector of nuclear photosynthetic gene expression, as previously reported. Moreover, it suggests the possible implication of Mg protoporphyrin IX methylester, the product of CHLM, in chloroplast-to-nucleus signaling. Finally, post-transcriptional up-regulation of the level of the CHLH subunit of the Mg chelatase has been detected in the chlm mutant and most likely corresponds to specific accumulation of this protein inside plastids. This result suggests that the CHLH subunit might play an important regulatory role when the chlorophyll biosynthetic pathway is disrupted at this particular step. PMID:17135235

  5. δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

    PubMed Central

    Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

    2011-01-01

    Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

  6. Use of proteomics for validation of the isolation process of clotting factor IX from human plasma.

    PubMed

    Clifton, James; Huang, Feilei; Gaso-Sokac, Dajana; Brilliant, Kate; Hixson, Douglas; Josic, Djuro

    2010-01-03

    The use of proteomic techniques in the monitoring of different production steps of plasma-derived clotting factor IX (pd F IX) was demonstrated. The first step, solid-phase extraction with a weak anion-exchange resin, fractionates the bulk of human serum albumin (HSA), immunoglobulin G, and other non-binding proteins from F IX. The proteins that strongly bind to the anion-exchange resin are eluted by higher salt concentrations. In the second step, anion-exchange chromatography, residual HSA, some proteases and other contaminating proteins are separated. In the last chromatographic step, affinity chromatography with immobilized heparin, the majority of the residual impurities are removed. However, some contaminating proteins still remain in the eluate from the affinity column. The next step in the production process, virus filtration, is also an efficient step for the removal of residual impurities, mainly high molecular weight proteins, such as vitronectin and inter-alpha inhibitor proteins. In each production step, the active component, pd F IX and contaminating proteins are monitored by biochemical and immunochemical methods and by LC-MS/MS and their removal documented. Our methodology is very helpful for further process optimization, rapid identification of target proteins with relatively low abundance, and for the design of subsequent steps for their removal or purification.

  7. Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

    PubMed

    Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

    2016-03-01

    Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

  8. Ares I-X: Lessons for a New Era of Spaceflight

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.

    2010-01-01

    Since 2005, the Ares Projects at Marshall Space Flight Center (MSFC) have been developing the Ares I crew launch vehicle and Ares V cargo launch vehicle. On October 28, 2009, the first development flight test of the Ares I crew launch vehicle, Ares I-X, lifted off from a launch pad at Kennedy Space Center (KSC) on successful suborbital flight. Despite the President s intention to cancel the Constellation Program of which Ares is a part, this historic flight has produced a great amount of data and numerous lessons learned for any future launch vehicles. This paper will describe the accomplishments of Ares I-X and the lessons that other programs can glean from this successful mission. Ares I was designed to carry up to four astronauts to the International Space Station (ISS). It also was designed to be used with the Ares V cargo launch vehicle for a variety of missions beyond low-Earth orbit (LEO). The Ares I-X development flight test was conceived in 2006 to acquire early engineering and environment data during liftoff, ascent, and first stage recovery. The test achieved the following primary objectives: Demonstrated control of a dynamically similar, integrated Ares I/Orion, using Ares I relevant ascent control algorithms. Performed an in-flight separation/staging event between a Ares I-similar First Stage and a representative Upper Stage. Demonstrated assembly and recovery of a new Ares I-like First Stage element at KSC. Demonstrated First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics, and parachute performance. Characterized the magnitude of integrated vehicle roll torque throughout First Stage flight.

  9. Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

    2016-04-25

    Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process.

  10. Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation

    PubMed Central

    2013-01-01

    Background Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster. Results A set of plasma membrane-resident zinc transporters was identified to be responsible for absorbing zinc from the lumen into the enterocyte and the subsequent exit of zinc to the circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Exit of zinc to the circulation is mediated through another two functionally overlapping zinc exporters, dZnT1, and its homolog CG5130 (dZnT77C). Somewhat surprisingly, it appears that the array of intracellular ZnT proteins, including the Golgi-resident dZnT7, is not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that regulation of dietary zinc absorption, in contrast to that of iron, is unresponsive to bodily needs or zinc status outside the gut. The zinc transporters that are involved in dietary zinc absorption, including the importers dZip1 and dZip2, and the exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte. Conclusions Our study using the model organism Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulatory control, a process that is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies, and also enable an appreciation of this important process from an evolutionary perspective. PMID:24063361

  11. "To Study the Relationship of Academic Stress and Socio-Economic Status among IX Standard Students of Raipur City"

    ERIC Educational Resources Information Center

    Khan, Suhail Ahmed; Ayyub, Khan Farhat

    2013-01-01

    This paper focuses on the relationship between academic stress and socio-economic status among IX standard students. The research was carried out in Raipur City (Chhattisgarh) on a sample of 600 IX standard students of English and Hindi medium schools. Academic Stress was measured by Stress Inventory for School Students prepared by Seema Rani…

  12. Classification of ASASSN-18ix as a dwarf nova

    NASA Astrophysics Data System (ADS)

    Aydi, E.; Buckley, D. A. H.; Mohamed, S.; Whitelock, P. A.; Chomiuk, L.; Strader, J.; Stanek, K. Z.

    2018-05-01

    We report on SALT high-resolution spectroscopy of ASASSN-18ix which was reported as a possible Galactic nova by K. Z. Stanek et al. (ATel #11561). We obtained a 2000 s spectrum of this object under the SALT Large Science Program on transients on 2018 April 24.99 (HJD 2458233.50), using the High Resolution Spectrograph (HRS; Crause et al. 2014, Proc.

  13. Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

    NASA Astrophysics Data System (ADS)

    Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

    1995-03-01

    Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

  14. Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer.

    PubMed

    Buchlis, George; Podsakoff, Gregory M; Radu, Antonetta; Hawk, Sarah M; Flake, Alan W; Mingozzi, Federico; High, Katherine A

    2012-03-29

    In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.

  15. Intracellular localization analysis of npAu-PpIX in HeLa cells using specific dyes and confocal microscopy

    NASA Astrophysics Data System (ADS)

    Roblero-Bartolón, Victoria Gabriela; Maldonado-Alvarado, Elizabeth; Galván-Mendoza, José Iván; Ramón-Gallegos, Eva

    2012-10-01

    Cervical carcinoma (CC) represents the second leading cause of cancer death in Mexican women. No conventional treatments are being developed such as photodynamic therapy (PDT), involving the simultaneous presence of a photosensitizer (Ps), light of a specific wavelength and tissue oxygen. On the other hand, it has seen that the use of gold nanoparticles coupled to protoporphyrin IX increases the effectiveness of PDT. The aim of this study was to determine the site of accumulation of the conjugate npAu-PpIX in cells of cervical cancer by the use of specific dyes and confocal microscopy. The results indicate that the gold nanoparticles coupled to protoporphyrin IX are accumulated in both the cytoplasm and nucleus of HeLa cells.

  16. 77 FR 64401 - Order of Succession for HUD Region IX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... Urban Development, designates the Order of Succession for the San Francisco Regional Office and its... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [FR-5550-D-12] Order of Succession for HUD Region IX... Development, 451 7th Street SW., Room 9262, Washington, DC 20410-0500, telephone number 202-402-3502 (this is...

  17. Specific Binding of Protoporphyrin IX to a Membrane-Bound 63 Kilodalton Polypeptide in Cucumber Cotyledons Treated with Diphenyl Ether-Type Herbicides.

    PubMed

    Sato, R; Oshio, H; Koike, H; Inoue, Y; Yoshida, S; Takahashi, N

    1991-06-01

    Porphyrin accumulation in excised cucumber cotyledons (Cucumis sativus L.) treated with a N-phenylimide S-23142 (N-[4-chloro-2-fluoro-5-propargyloxyphenyl]-3,4,5,6- tetrahydrophthalimide) and a diphenylether acifluorfen-ethyl (ethyl-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitro benzoic acid) was studied. Most of the accumulated porphyrins were found in the membrane fractions of 6,000g and 30,000g pellets, forming a complex with a membrane polypeptide. The complex was solubilized with 1% n-dodecyl beta-d-maltoside and its molecular mass was estimated to be 63,000 and 66,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel permeation high performance liquid chromatography (HPLC), respectively. The polypeptide also existed in untreated cotyledons but had little protoporphyrin IX. The complex was also formed in vitro by mixing the 30,000g pellets from untreated cotyledons and authentic protoporphyrin IX. However, protoporphyrin IX formed the complex specifically with the 63,000 dalton polypeptide and not with the other proteins both in vivo and in vitro. At least four fluorescent porphyrins, including protoporphyrin IX, were found in the acetone extract of the cotyledons by HPLC using a reversed phase column. Protoporphyrin IX was one of the two porphyrins that formed the complex. These results suggest that S-23142 and acifluorfenethyl enhance the accumulation of protoporphyrin IX, which forms the complex with the membrane protein.

  18. Zinc triggers microglial activation.

    PubMed

    Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

    2008-05-28

    Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

  19. The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

    PubMed Central

    Tran, Cuong D.; Gopalsamy, Geetha L.; Mortimer, Elissa K.; Young, Graeme P.

    2015-01-01

    It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease. PMID:26035248

  20. Zinc Information

    MedlinePlus

    ... for Eye Conditions Clinical Digest: Hepatitis C and Dietary Supplements Related Resources From Other Agencies Age-Related Eye Disease Study 2 (AREDS2) ( NEI ) Can Zinc Be Harmful? ( ODS ) Zinc ( ODS ) Follow NCCIH: Read our disclaimer ...

  1. Zinc starvation induces autophagy in yeast

    PubMed Central

    Kawamata, Tomoko; Horie, Tetsuro; Matsunami, Miou; Sasaki, Michiko; Ohsumi, Yoshinori

    2017-01-01

    Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. PMID:28264932

  2. DISTRIBUTION OF MERCURY IN USEPA REGION IX R-EMAP STUDY AREAS

    EPA Science Inventory

    Mercury distribution within U .S. EP A Region IX Regional Environmental Monitoring and Assessment Program (R-EMAP) study units is associated with geology and land-use practices. Stream water and sediment data indicate mercury is mobilized from weathering of ore bearing rock, and ...

  3. ARES I-X: The First Test Flight of a New Era

    NASA Technical Reports Server (NTRS)

    Smith, R. Marshall; Davis, Stephan R.; Bryant, Richard Barry; Cook, Steve

    2010-01-01

    On October 28th, 2009, the National Aeronautics and Space Administration (NASA) launched the Ares I-X Flight Test Vehicle (FTV) from pad 39B, providing the first set of flight test data for NASA's Ares I vehicle design team. This test was critical in providing insight into areas were significant design challenges existed. This paper discusses the objectives of the mission and how they were satisfied. It discusses the overall results of the flight test and look at the data retrieved from the flight. Ares I-X was highly instrumented with over 700 channels of Developmental Flight Instrumentation (DFI). Significant insight was gained in the areas of thrust oscillation, vibro-acoustics, predicting jet interactions and slag ejection from solid rocket systems with submerged nozzles. The paper outlines results from the Guidance Navigation & Control (GN&C), Thermal, Vibro-acoustic, Structures, Aero, Aero-Acoustic and Trajectory teams.

  4. Studies on the bioavailability of zinc in humans: intestinal interaction of tin and zinc.

    PubMed

    Solomons, N W; Marchini, J S; Duarte-Favaro, R M; Vannuchi, H; Dutra de Oliveira, J E

    1983-04-01

    Mineral/mineral interactions at the intestinal level are important in animal nutrition and toxicology, but only limited understanding of their extent or importance in humans has been developed. An inhibitory interaction of dietary tin on zinc retention has been recently described from human metabolic studies. We have explored the tin/zinc interaction using the change-in-plasma-zinc-concentration method with a standard dosage of 12.5 mg of zinc as zinc sulfate in 100 ml of Coca-Cola. Sn/Zn ratios of 2:1, 4:1, and 8:1, constituted by addition of 25, 50, and 100 mg of tin as stannous chloride, had no significant overall effect on zinc uptake. The 100-mg dose of tin produced noxious gastrointestinal symptoms. Addition of iron as ferrous sulfate to form ratios of Sn/Fe/Zn of 1:1:1 and 2:2:1 with the standard zinc solution and the appropriate doses of tin produced a reduction of zinc absorption not dissimilar from that seen previously with zinc and iron alone, and addition of picolinic acid did not influence the uptake of zinc from the solution with the 2:2:1 Sn/Fe/Zn ratio.

  5. Suppression of zinc dendrites in zinc electrode power cells

    NASA Technical Reports Server (NTRS)

    Damjanovic, A.; Diggle, J. W.

    1970-01-01

    Addition of various tetraalkyl quarternary ammonium salts, to alkaline zincate electrolyte of cell, prevents formation of zinc dendrites during charging of zinc electrode. Electrode capacity is not impaired and elimination of dendrites prolongs cell life.

  6. Zinc triggers microglial activation

    PubMed Central

    Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

    2009-01-01

    Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

  7. Zinc starvation induces autophagy in yeast.

    PubMed

    Kawamata, Tomoko; Horie, Tetsuro; Matsunami, Miou; Sasaki, Michiko; Ohsumi, Yoshinori

    2017-05-19

    Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Antibody Fab display and selection through fusion to the pIX coat protein of filamentous phage.

    PubMed

    Tornetta, Mark; Baker, Scott; Whitaker, Brian; Lu, Jin; Chen, Qiang; Pisors, Eileen; Shi, Lei; Luo, Jinquan; Sweet, Raymond; Tsui, Ping

    2010-08-31

    Fab antibody display on filamentous phage is widely applied to de novo antibody discovery and engineering. Here we describe a phagemid system for the efficient display and affinity selection of Fabs through linkage to the minor coat protein pIX. Display was successful by fusion of either Fd or Lc through a short linker to the amino terminus of pIX and co-expression of the counter Lc or Fd as a secreted, soluble fragment. Assembly of functional Fab was confirmed by demonstration of antigen-specific binding using antibodies of known specificity. Phage displaying a Fab specific for RSV-F protein with Fd linked to pIX showed efficient, antigen-specific enrichment when mixed with phage displaying a different specificity. The functionality of this system for antibody engineering was evaluated in an optimization study. A RSV-F protein specific antibody with an affinity of about 2nM was randomized at 4 positions in light chain CDR1. Three rounds of selection with decreasing antigen concentration yielded Fabs with an affinity improvement up to 70-fold and showed a general correlation between enrichment frequency and affinity. We conclude that the pIX coat protein complements other display systems in filamentous phage as an efficient vehicle for low copy display and selection of Fab proteins. 2010 Elsevier B.V. All rights reserved.

  9. Two novel mutations in the PPIB gene cause a rare pedigree of osteogenesis imperfecta type IX.

    PubMed

    Jiang, Yu; Pan, Jingxin; Guo, Dongwei; Zhang, Wei; Xie, Jie; Fang, Zishui; Guo, Chunmiao; Fang, Qun; Jiang, Weiying; Guo, Yibin

    2017-06-01

    Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder characterized by increased bone fragility and vulnerability to fractures. PPIB is identified as a candidate gene for OI-IX, here we detect two pathogenic mutations in PPIB and analyze the genotype-phenotype correlation in a Chinese family with OI. Next-generation sequencing (NGS) was used to screen the whole exome of the parents of proband. Screening of variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations. Sanger sequencing was used to confirm the candidate variants. RTQ-PCR was used to analyze the PPIB gene expression. All mutant genes screened out by NGS were excluded except PPIB. Two novel heterozygous PPIB mutations (father, c.25A>G; mother, c.509G>A) were identified in relation to osteogenesis imperfecta type IX. Both mutations were predicted to be pathogenic by bioinformatics analysis and RTQ-PCR analysis revealed downregulated PPIB expression in the two carriers. We report a rare pedigree with an autosomal recessive osteogenesis imperfecta type IX (OI-IX) caused by two novel PPIB mutations identified for the first time in China. The current study expands our knowledge of PPIB mutations and their associated phenotypes, and provides new information on the genetic defects associated with this disease for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Supplemental levels of iron and calcium interfere with repletion of zinc status in zinc-deficient animals.

    PubMed

    Jayalakshmi, S; Platel, Kalpana

    2016-05-18

    Negative interactions between minerals interfering with each other's absorption are of concern when iron and calcium supplements are given to pregnant women and children. We have previously reported that supplemental levels of iron and calcium inhibit the bioaccessibility of zinc, and compromise zinc status in rats fed diets with high levels of these two minerals. The present study examined the effect of supplemental levels of iron and calcium on the recovery of zinc status during a zinc repletion period in rats rendered zinc-deficient. Iron and calcium, both individually and in combination, significantly interfered with the recovery of zinc status in zinc deficient rats during repletion with normal levels of zinc in the diet. Rats maintained on diets containing supplemental levels of these two minerals had significantly lower body weight, and the concentration of zinc in serum and organs was significantly lower than in zinc-deficient rats not receiving the supplements. Iron and calcium supplementation also significantly inhibited the activity of zinc-containing enzymes in the serum as well as liver. Both iron and calcium independently exerted this negative effect on zinc status, while their combination seemed to have a more prominent effect, especially on the activities of zinc containing enzymes. This investigation is probably the first systematic study on the effect of these two minerals on the zinc status of zinc deficient animals and their recovery during repletion with normal amounts of zinc.

  11. Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla.

    PubMed

    Fries, P; Morr, D; Müller, A; Lux, F; Tillement, O; Massmann, A; Seidel, R; Schäfer, T; Menger, M D; Schneider, G; Bücker, A

    2015-12-01

    The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm(2), matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 +/- 0.7; AGuIX: 28.2+/- 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/- 1.2; AGuIX: 29.6 +/- 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/- 0.7; AGuIX: 15.4 +/- 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/- 0.3; AGuIX: 14.0 +/- 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 +/- 0.2; AGuIX: -7.5 +/- 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/- 0.7; AGuIX: 14.9 +/- 2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors. AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T. AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions. The small size

  12. Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

    PubMed Central

    Bekelis, Kimon; Valdés, Pablo A.; Erkmen, Kadir; Leblond, Frederic; Kim, Anthony; Wilson, Brian C.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection. Methods A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches. Results The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological

  13. Ares I-X First Stage Separation Loads and Dynamics Reconstruction

    NASA Technical Reports Server (NTRS)

    Demory, Lee; Rooker, BIll; Jarmulowicz, Marc; Glaese, John

    2011-01-01

    The Ares I-X flight test provided NASA with the opportunity to test hardware and gather critical data to ensure the success of future Ares I flights. One of the primary test flight objectives was to evaluate the environment during First Stage separation to better understand the conditions that the J-2X second stage engine will experience at ignition [1]. A secondary objective was to evaluate the effectiveness of the stage separation motors. The Ares I-X flight test vehicle was successfully launched on October 29, 2009, achieving most of its primary and secondary test objectives. Ground based video camera recordings of the separation event appeared to show recontact of the First Stage and the Upper Stage Simulator followed by an unconventional tumbling of the Upper Stage Simulator. Closer inspection of the videos and flight test data showed that recontact did not occur. Also, the motion during staging was as predicted through CFD analysis performed during the Ares I-X development. This paper describes the efforts to reconstruct the vehicle dynamics and loads through the staging event by means of a time integrated simulation developed in TREETOPS, a multi-body dynamics software tool developed at NASA [2]. The simulation was built around vehicle mass and geometry properties at the time of staging and thrust profiles for the first stage solid rocket motor as well as for the booster deceleration motors and booster tumble motors. Aerodynamic forces were determined by models created from a combination of wind tunnel testing and CFD. The initial conditions such as position, velocity, and attitude were obtained from the Best Estimated Trajectory (BET), which is compiled from multiple ground based and vehicle mounted instruments. Dynamic loads were calculated by subtracting the inertial forces from the applied forces. The simulation results were compared to the Best Estimated Trajectory, accelerometer flight data, and to ground based video.

  14. [A Jehovah's Witness child with hemophilia B and factor IX inhibitors undergoing scoliosis surgery].

    PubMed

    Chau, Anthony; Wu, John; Ansermino, Mark; Tredwell, Stephen; Purdy, Robert

    2008-01-01

    To describe the successful perioperative hemostatic management of a Jehovah's Witness patient with hemophilia B and anaphylactic inhibitors to factor IX, undergoing scoliosis surgery. A 14 (1/2)-yr-old boy with severe hemophilia B who had a history of anaphylactic inhibitors to factor IX was scheduled to undergo corrective scoliosis surgery. He was initially started on epoetin alfa and iron supplementation to maximize preoperative red cell mass. Additionally, he was placed on a desensitization protocol of recombinant coagulation factor IX (rFIX) and was then treated with activated recombinant coagulation factor VII (rFVIIa) during the postoperative period. Tranexamic acid was given concomitantly. The intraoperative blood loss was approximately 350 mL. The nadir hemoglobin concentration was 111 g.L(-1) on postoperative days one and two. On postoperative day 11, the patient was stable and discharged home with a hemoglobin of 138 g.L(-1). He did not require blood transfusion and no adverse events were observed. The use of rFIX, rFVIIa, erythropoetin, iron, and tranexamic acid before, during and after scoliosis surgery may be a viable and safe option for hemophilia patients with inhibitors, who refuse blood products.

  15. [Zinc and chronic enteropathies].

    PubMed

    Giorgi, P L; Catassi, C; Guerrieri, A

    1984-01-01

    In recent years the nutritional importance of zinc has been well established; its deficiency and its symptoms have also been recognized in humans. Furthermore, Acrodermatitis Enteropathica has been isolated, a rare but severe disease, of which skin lesions, chronic diarrhoea and recurring infections are the main symptoms. The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally. Good dietary sources of zinc are meat, fish and, to a less extent, human milk. The amount of zinc absorbed in the small intestine is influenced by other nutrients: some compounds inhibit this process (dietary fiber, phytate) while others (picolinic acid, citric acid), referred to as Zn-binding ligands (ZnBL) facilitate it. Citric acid is thought to be the ligand which accounts for the high level of bioavailability of zinc in human milk. zinc absorption occurs throughout the small intestine, not only in the prossimal tract (duodenum and jejunum) but also in the distal tract (ileum). Diarrhoea is one of the clinical manifestations of zinc deficiency, thus many illnesses distinguished by chronic diarrhoea entail a bad absorption of zinc. In fact, in some cases of chronic enteropathies in infants, like coeliac disease and seldom cystic fibrosis, a deficiency of zinc has been isolated. Some of the symptoms of Crohn's disease, like retarded growth and hypogonadism, have been related to hypozinchemia which is present in this illness. Finally, it is possible that some of the dietary treatments frequently used for persistent post-enteritis diarrhoea (i.e. cow's milk exclusion, abuse and misuse of dietary fiber like carrot and carub powder, use of soy formula) can constitute a scarce supply of zinc and therefore could promote the persistency of diarrhoea itself.

  16. Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy

    NASA Astrophysics Data System (ADS)

    Dong, Jiancheng; Ghiladi, Reza A.; Wang, Qingqing; Cai, Yibing; Wei, Qufu

    2018-06-01

    Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been ‘photo-aged’ with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.

  17. Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy.

    PubMed

    Dong, Jiancheng; Ghiladi, Reza A; Wang, Qingqing; Cai, Yibing; Wei, Qufu

    2018-06-29

    Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been 'photo-aged' with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.

  18. Zinc oxyfluoride transparent conductor

    DOEpatents

    Gordon, Roy G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400.degree. C. to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings.

  19. 5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review.

    PubMed

    Guyotat, Jacques; Pallud, Johan; Armoiry, Xavier; Pavlov, Vladislav; Metellus, Philippe

    2016-01-01

    The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don't permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival).

  20. Zinc Extraction from Zinc Plants Residue Using Selective Alkaline Leaching and Electrowinning

    NASA Astrophysics Data System (ADS)

    Ashtari, Pedram; Pourghahramani, Parviz

    2015-10-01

    Annually, a great amount of zinc plants residue is produced in Iran. One of them is hot filter cake (known as HFC) which can be used as a secondary resource of zinc, cobalt and manganese. Unfortunately, despite its heavy metal content, the HFC is not treated. For the first time, zinc was selectively leached from HFC employing alkaline leaching. Secondly, leaching was optimized to achieve maximum recovery using this method. Effects of factors like NaOH concentration (C = 3, 5, 7 and 9 M), temperature (T = 50, 70, 90 and 105 °C), solid/liquid ratio (weight/volume, S/L = 1/10 and 1/5 W/V) and stirring speed (R = 500 and 800 rpm) were studied on HFC leaching. L16 orthogonal array (OA, two factors in four levels and two factors in two levels) was applied to determine the optimum condition and the most significant factor affecting the overall zinc extraction. As a result, maximum zinc extraction was 83.4 %. Afterwards, a rough test was conducted for zinc electrowinning from alkaline solution according to the common condition available in literature by which pure zinc powder (99.96 %) was successfully obtained.

  1. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

    USDA-ARS?s Scientific Manuscript database

    To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

  2. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  3. Structure of the Type IX Group B Streptococcus Capsular Polysaccharide and Its Evolutionary Relationship with Types V and VII

    PubMed Central

    Berti, Francesco; Campisi, Edmondo; Toniolo, Chiara; Morelli, Laura; Crotti, Stefano; Rosini, Roberto; Romano, Maria Rosaria; Pinto, Vittoria; Brogioni, Barbara; Torricelli, Giulia; Janulczyk, Robert; Grandi, Guido; Margarit, Immaculada

    2014-01-01

    The Group B Streptococcus capsular polysaccharide type IX was isolated and purified, and the structure of its repeating unit was determined. Type IX capsule →4)[NeupNAc-α-(2→3)-Galp-β-(1→4)-GlcpNAc-β-(1→6)]-β-GlcpNAc-(1→4)-β-Galp-(1→4)-β-Glcp-(1→ appears most similar to types VII and V, although it contains two GlcpNAc residues. Genetic analysis identified differences in cpsM, cpsO, and cpsI gene sequences as responsible for the differentiation between the three capsular polysaccharide types, leading us to hypothesize that type V emerged from a recombination event in a type IX background. PMID:24990951

  4. Ares I-X USS Material Testing

    NASA Technical Reports Server (NTRS)

    Dawicke, David S.; Smith, Stephen W.; Raju, Ivatury S.

    2008-01-01

    An independent assessment was conducted to determine the critical initial flaw size (CIFS) for the flange-to-skin weld in the Ares I-X Upper Stage Simulator (USS). Material characterization tests were conducted to quantify the material behavior for use in the CIFS analyses. Fatigue crack growth rate, Charpy impact, and fracture tests were conducted on the parent and welded A516 Grade 70 steel. The crack growth rate tests confirmed that the material behaved in agreement with literature data and that a salt water environment would not significantly degrade the fatigue resistance. The Charpy impact tests confirmed that the fracture resistance of the material did not have a significant reduction for the expected operational temperatures of the vehicle.

  5. Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation.

    PubMed

    Hashimoto, Ayako; Nakagawa, Miki; Tsujimura, Natsuki; Miyazaki, Shiho; Kizu, Kumiko; Goto, Tomoko; Komatsu, Yusuke; Matsunaga, Ayu; Shirakawa, Hitoshi; Narita, Hiroshi; Kambe, Taiho; Komai, Michio

    2016-03-01

    Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely. Copyright © 2016 the American Physiological Society.

  6. Interaction Between Yeasts and Zinc

    NASA Astrophysics Data System (ADS)

    Nicola, Raffaele De; Walker, Graeme

    Zinc is an essential trace element in biological systems. For example, it acts as a cellular membrane stabiliser, plays a critical role in gene expression and genome modification and activates nearly 300 enzymes, including alcohol dehydrogenase. The present chapter will be focused on the influence of zinc on cell physiology of industrial yeast strains of Saccharomyces cerevisiae, with special regard to the uptake and subsequent utilisation of this metal. Zinc uptake by yeast is metabolism-dependent, with most of the available zinc translocated very quickly into the vacuole. At cell division, zinc is distributed from mother to daughter cells and this effectively lowers the individual cellular zinc concentration, which may become zinc depleted at the onset of the fermentation. Zinc influences yeast fermentative performance and examples will be provided relating to brewing and wine fermentations. Industrial yeasts are subjected to several stresses that may impair fermentation performance. Such stresses may also impact on yeast cell zinc homeostasis. This chapter will discuss the practical implications for the correct management of zinc bioavailability for yeast-based biotechnologies aimed at improving yeast growth, viability, fermentation performance and resistance to environmental stresses

  7. Cellular pH and PI3K signaling as determinants of Protoporphyrin IX conversion and ALA PDT response

    NASA Astrophysics Data System (ADS)

    Anderson, Michael; El-Hamidi, Hamid; Celli, Jonathan

    2018-02-01

    ALA PDT is a FDA approved cancer treatment. The general model is that excess exogenous ALA is eventually converted to the active photosensitizer, PpIX, and accumulates PpIX to concentrations well above baseline. This accumulation, however, varies considerable from person to person and even intra-tumorally due to a high number of factors that are involved. Due to this there is an increasing desire to pair ALA PDT with other treatments to enhance the efficacy of PDT. This idea itself isn't new as the labs of Bin Chen and Edward Maytin have a long history of using biology to enhance PpIX accumulation. The PI3K pathway is a long-studied cancer treatment target due to it being one of the most ubiquitous over expressed pathways in cancer and that many treatments have demonstrated enhanced efficacy upon PI3K inhibition. In this paper we show that the PI3K pathway inhibitor, LY294002, alters PpIX accumulation in cells (decreased for A431 and increases for Panc-1 and Panc-1 OR) and significantly increases the efficacy of ALA PDT in every case for both monolayer and spheroid cultures. Additionally, we show that PDT treatments using the nonendogenous photosensitizer, verteporfin, also have enhanced efficacy upon PI3K inhibition. Beyond the treatment synergy of PI3K inhibition and PDT, this work presents a cell pairing model that is perfect to study the previously, to our knowledge, undocumented connection between the PI3K pathway and PpIX accumulation.

  8. Immunogenicity and immune tolerance coagulation Factors VIII and IX.

    PubMed

    Rup, B

    2003-01-01

    Some of the major issues related to the development and control of antibodies that occur during treatment of haemophilia with replacement factors (Factor VIII and Factor IX) are reviewed. Information on analytical issues, immunogenicity, and immune tolerance may be applicable to the study of other therapeutic proteins. Conversely, new information obtained from evaluation of other therapeutic protein products may address issues that remain unresolved for Factor VIII and FIX replacement therapy.

  9. Generalized Quantum Theory of Bianchi IX Cosmologies

    NASA Astrophysics Data System (ADS)

    Craig, David; Hartle, James

    2003-04-01

    We apply sum-over-histories generalized quantum theory to the closed homogeneous minisuperspace Bianchi IX cosmological model. We sketch how the probabilities in decoherent sets of alternative, coarse-grained histories of this model universe are calculated. We consider in particular, the probabilities for classical evolution in a suitable coarse-graining. For a restricted class of initial conditions and coarse grainings we exhibit the approximate decoherence of alternative histories in which the universe behaves classically and those in which it does not, illustrating the prediction that these universes will evolve in an approximately classical manner with a probability near unity.

  10. Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII.

    PubMed

    Kumar, Satish; Ceruso, Mariangela; Tuccinardi, Tiziano; Supuran, Claudiu T; Sharma, Pawan K

    2016-07-01

    Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Sex Discrimination and Intercollegiate Athletics: Putting Some Muscle on Title IX.

    ERIC Educational Resources Information Center

    Yale Law Journal, 1979

    1979-01-01

    Argues that the general language of the Title IX statute, together with certain specific features of it, strongly suggests that the Department of Health, Education, and Welfare should develop more stringent and demanding regulations based on social policy considerations concerning sex discrimination in intercollegiate sports. Available from Yale…

  12. Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

    USGS Publications Warehouse

    Flinn, J.M.; Hunter, D.; Linkous, D.H.; Lanzirotti, A.; Smith, L.N.; Brightwell, J.; Jones, B.F.

    2005-01-01

    Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (??SXRF) confirmed that brain zinc levels were increased by adding ZnCO 3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function. ?? 2004 Elsevier Inc. All rights reserved.

  13. [Advances in the research of zinc deficiency and zinc supplementation treatment in patients with severe burns].

    PubMed

    Wang, X X; Zhang, M J; Li, X B

    2018-01-20

    Zinc is one of the essential trace elements in human body, which plays an important role in regulating acute inflammatory response, glucose metabolism, anti-oxidation, immune and gastrointestinal function of patients with severe burns. Patients with severe burns may suffer from zinc deficiency because of insufficient amount of zinc intake from the diet and a large amount of zinc lose through wounds and urine. Zinc deficiency may affect their wound healing process and prognosis. This article reviews the characteristics of zinc metabolism in patients with severe burns through dynamic monitoring the plasma and urinary concentration of zinc. An adequate dosage of zinc supplemented to patients with severe burns by an appropriate method can increase the level of zinc in plasma and skin tissue and improve wound healing, as well as reduce the infection rates and mortality. At the same time, it is important to observe the symptoms and signs of nausea, dizziness, leukopenia and arrhythmia in patients with severe burns after supplementing excessive zinc.

  14. A systematic quantitative approach to rational drug design and discovery of novel human carbonic anhydrase IX inhibitors.

    PubMed

    Sethi, Kalyan K; Verma, Saurabh M

    2014-08-01

    Drug design involves the design of small molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of carbonic anhydrase IX inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques with the help of SYBYL 7.1 software. The large set of 36 different aromatic/heterocyclic sulfamates carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, such as hCA IX, was chosen for this study. The conventional ligand-based 3D-QSAR studies were performed based on the low energy conformations employing database alignment rule. The ligand-based model gave q(2) values 0.802 and 0.829 and r(2) values 1.000 and 0.994 for CoMFA and CoMSIA, respectively, and the predictive ability of the model was validated. The predicted r(2) values are 0.999 and 0.502 for CoMFA and CoMSIA, respectively. SEA (steric, electrostatic, hydrogen bond acceptor) of CoMSIA has the significant contribution for the model development. The docking of inhibitors into hCA IX active site using Glide XP (Schrödinger) software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps are well in agreement with the structural characteristics of the binding pocket of hCA IX active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved hCA IX inhibitors as leads for various types of metastatic cancers including those of cervical, renal, breast and head and neck origin.

  15. 99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON ...

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

    99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, LOOKING NORTH. NOTE ONE STYLE OF DENVER AGITATOR IN LOWER RIGHT CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  16. Serum thymulin in human zinc deficiency.

    PubMed Central

    Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

    1988-01-01

    The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

  17. Zinc supplementation in public health.

    PubMed

    Penny, Mary Edith

    2013-01-01

    Zinc is necessary for physiological processes including defense against infections. Zinc deficiency is responsible for 4% of global child morbidity and mortality. Zinc supplements given for 10-14 days together with low-osmolarity oral rehydration solution (Lo-ORS) are recommended for the treatment of childhood diarrhea. In children aged ≥ 6 months, daily zinc supplements reduce the duration of acute diarrhea episodes by 12 h and persistent diarrhea by 17 h. Zinc supplements could reduce diarrhea mortality in children aged 12-59 months by an estimated 23%; they are very safe but are associated with an increase in vomiting especially with the first dose. Heterogeneity between the results of trials is not understood but may be related to dose and the etiology of the diarrhea infection. Integration of zinc and Lo-ORS into national programs is underway but slowly, procurement problems are being overcome and the greatest challenge is changing health provider and caregiver attitudes to diarrhea management. Fewer trials have been conducted of zinc adjunct therapy in severe respiratory tract infections and there is as yet insufficient evidence to recommend addition of zinc to antibiotic therapy. Daily zinc supplements for all children >12 months of age in zinc deficient populations are estimated to reduce diarrhea incidence by 11-23%. The greatest impact is in reducing multiple episodes of diarrhea. The effect on duration of diarrheal episodes is less clear, but there may be up to 9% reduction. Zinc is also efficacious in reducing dysentery and persistent diarrhea. Zinc supplements may also prevent pneumonia by about 19%, but heterogeneity across studies has not yet been explained. When analyses are restricted to better quality studies using CHERG (Child Health Epidemiology Reference Group) methodology, zinc supplements are estimated to reduce diarrheal deaths by 13% and pneumonia deaths by 20%. National-level programs to combat childhood zinc deficiency should be

  18. Extreme ultraviolet spectra of S IX and S X relevant to solar coronal plasmas

    NASA Astrophysics Data System (ADS)

    Ali, Safdar; Kato, Hiroyuki; Nakamura, Nobuyuki

    2017-10-01

    We present extreme ultraviolet laboratory spectra of highly charged S IX and S X measured using a compact electron beam ion trap. The data were recorded using a flat-field grazing incidence spectrometer in the wavelength range between 210 and 290 Å. The beam energy was tuned for three different values at 365, 410 and 465 eV while keeping electron beam current constant at 10 mA. By measuring the beam energy dependence, we identified several lines originating from S IX and S X ions with the support of collisional-radiative modeling. We compared them with the present calculations and transitions listed in the NIST data base and found in good agreement.

  19. Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall.

    PubMed

    Middelburg, T A; de Bruijn, H S; Tettero, L; van der Ploeg van den Heuvel, A; Neumann, H A M; de Haas, E R M; Robinson, D J

    2013-09-05

    Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. History of Zinc in Agriculture12

    PubMed Central

    Nielsen, Forrest H.

    2012-01-01

    Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application. PMID:23153732

  1. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  2. Measurements of zinc absorption: application and interpretation in research designed to improve human zinc nutriture.

    PubMed

    Hambidge, K Michael; Miller, Leland V; Tran, Cuong D; Krebs, Nancy F

    2005-11-01

    The focus of this paper is on the application of measurements of zinc absorption in human research, especially studies designed to assess the efficacy of intervention strategies to prevent and manage zinc deficiency in populations. Emphasis is given to the measurement of quantities of zinc absorbed rather than restricting investigations to measurements of fractional absorption of zinc. This is especially important when determining absorption of zinc from the diet, whether it be the habitual diet or an intervention diet under evaluation. Moreover, measurements should encompass all meals for a minimum of one day with the exception of some pilot studies. Zinc absorption is primarily via an active saturable transport process into the enterocytes of the proximal small intestine. The relationship between quantity of zinc absorbed and the quantity ingested is best characterized by saturable binding models. When applied to human studies that have sufficient data to examine dose-response relationships, efficiency of absorption is high until approximately 50-60% maximal absorption is achieved, even with moderate phytate intakes. This also coincides approximately with the quantity of absorbed zinc necessary to meet physiologic requirements. Efficiency of absorption with intakes that exceed this level is low or very low. These observations have important practical implications for the design and interpretation of intervention studies to prevent zinc deficiency. They also suggest the potential utility of measurements of the quantity of zinc absorbed when evaluating the zinc status of populations.

  3. Ares I-X Best Estimated Trajectory and Comparison with Pre-Flight Predictions

    NASA Technical Reports Server (NTRS)

    Karlgaard, Christopher D.; Beck, Roger E.; Derry, Stephen D.; Brandon, Jay M.; Starr, Brett R.; Tartabini, Paul V.; Olds, Aaron D.

    2011-01-01

    The Ares I-X trajectory reconstruction produced best estimated trajectories of the flight test vehicle ascent through stage separation, and of the first and upper stage entries after separation. The trajectory reconstruction process combines on-board, ground-based, and atmospheric measurements to produce the trajectory estimates. The Ares I-X vehicle had a number of on-board and ground based sensors that were available, including inertial measurement units, radar, air- data, and weather balloons. However, due to problems with calibrations and/or data, not all of the sensor data were used. The trajectory estimate was generated using an Iterative Extended Kalman Filter algorithm, which is an industry standard processing algorithm for filtering and estimation applications. This paper describes the methodology and results of the trajectory reconstruction process, including flight data preprocessing and input uncertainties, trajectory estimation algorithms, output transformations, and comparisons with preflight predictions.

  4. Upper Atmospheric Monitoring for Ares I-X Ascent Loads and Trajectory Evaluation on the Day-of-Launch

    NASA Technical Reports Server (NTRS)

    Roberts, Barry C.; McGrath, Kevin; Starr, Brett; Brandon, Jay

    2009-01-01

    During the launch countdown of the Ares I-X test vehicle, engineers from Langley Research Center will use profiles of atmospheric density and winds in evaluating vehicle ascent loads and controllability. A schedule for the release of balloons to measure atmospheric density and winds has been developed by the Natural Environments Branch at Marshall Space Flight Center to help ensure timely evaluation of the vehicle ascent loads and controllability parameters and support a successful launch of the Ares I-X vehicle.

  5. Interaction of zinc with dental mineral.

    PubMed

    Ingram, G S; Horay, C P; Stead, W J

    1992-01-01

    As some currently available toothpastes contain zinc compounds, the reaction of zinc with dental mineral and its effect on crystal growth rates were studied using three synthetic calcium-deficient hydroxyapatites (HAP) as being representative of dental mineral. Zinc was readily acquired by all HAP samples in the absence of added calcium, the amount adsorbed being proportional to the HAP surface area; about 9 mumol Zn/m2 was adsorbed at high zinc concentrations. As zinc was acquired, calcium was released, consistent with 1:1 Ca:Zn exchange. Soluble calcium reduced zinc uptake and similarly, calcium post-treatment released zinc. Pretreatment of HAP with 0.5 mM zinc reduced its subsequent ability to undergo seeded crystal growth, as did extracts of a toothpaste containing 0.5% zinc citrate, even in the presence of saliva. The reverse reaction, i.e. displacement of adsorbed zinc by salivary levels of calcium, however, indicates the mechanism by which zinc can reduce calculus formation in vivo by inhibiting plaque mineralisation without adversely affecting the anti-caries effects of fluoride.

  6. Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

    DOEpatents

    Adler, T.C.; McLarnon, F.R.; Cairns, E.J.

    1994-04-12

    An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K[sub 2]CO[sub 3] salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics. 8 figures.

  7. Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

    DOEpatents

    Adler, Thomas C.; McLarnon, Frank R.; Cairns, Elton J.

    1994-01-01

    An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K.sub.2 CO.sub.3 salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics.

  8. Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc.

    PubMed

    Baltaci, Abdulkerim Kasım; Mogulkoc, Rasim

    2017-06-01

    Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT 3 , FT 4 , TT 3 , and TT 4 ) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.

  9. Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2015-06-01

    The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

  10. MYStIX: Dynamical evolution of young clusters

    NASA Astrophysics Data System (ADS)

    Kuhn, Michael A.

    2014-08-01

    The spatial structure of young stellar clusters in Galactic star-forming regions provides insight into these clusters’ dynamical evolution---a topic with implications for open questions in star-formation and cluster survival. The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) provides a sample of >30,000 young stars in star-forming regions (d<3.6 kpc) that contain at least one O-type star. We use the finite mixture model analysis to identify subclusters of stars and determine their properties: including subcluster radii, intrinsic numbers of stars, central density, ellipticity, obscuration, and age. In 17 MYStIX regions we find 142 subclusters, with a diverse radii and densities and age spreads of up to ~1 Myr in a region. There is a strong negative correlation between subcluster radius and density, which indicates that embedded subclusters expand but also gain stars as they age. Subcluster expansion is also shown by a positive radius--age correlation, which indicates that subclusters are expanding at <1 km/s. The subcluster ellipticity distribution and number--density relation show signs of a hierarchical merger scenario, whereby young stellar clusters are built up through mergers of smaller clumps, causing evolution from a clumpy spatial distribution of stars (seen in some regions) to a simpler distribution of stars (seen in other regions). Many of the simple young stellar clusters show signs of dynamically relaxation, even though they are not old enough for this to have occurred through two-body interactions. However, this apparent contradiction might be explained if small subcluster, which have shorter dynamical relaxation times, can produce dynamically relaxed clusters through hierarchical mergers.

  11. An Assessment of Ares I-X Aeroacoustic Measurements with Comparisons to Pre-Flight Wind Tunnel Test Results

    NASA Technical Reports Server (NTRS)

    Nance, Donald K.; Reed, Darren K.

    2011-01-01

    During the recent successful launch of the Ares I-X Flight Test Vehicle, aeroacoustic data was gathered at fifty-seven locations along the vehicle as part of the Developmental Flight Instrumentation. Several of the Ares I-X aeroacoustic measurements were placed to duplicate measurement locations prescribed in pre-flight, sub-scale wind tunnel tests. For these duplicated measurement locations, comparisons have been made between aeroacoustic data gathered during the ascent phase of the Ares I-X flight test and wind tunnel test data. These comparisons have been made at closely matching flight conditions (Mach number and vehicle attitude) in order to preserve a one-to-one relationship between the flight and wind tunnel data. These comparisons and the current wind tunnel to flight scaling methodology are presented and discussed. The implications of using wind tunnel test data scaled under the current methodology to predict conceptual launch vehicle aeroacoustic environments are also discussed.

  12. Zinc as a Gatekeeper of Immune Function

    PubMed Central

    Wessels, Inga; Maywald, Martina; Rink, Lothar

    2017-01-01

    After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function. PMID:29186856

  13. Different Duck Species Infected Intramuscularly with Duck-Origin Genotype IX APMV-1 Show Discrepant Mortality and Indicate Another Fatal Genotype APMV-1 to Ducks.

    PubMed

    Fu, Guanghua; Cheng, Longfei; Fu, Qiuling; Qi, Baomin; Chen, Cuiteng; Shi, Shaohua; Chen, Hongmei; Wan, Chunhe; Liu, Rongchang; Huang, Yu

    2017-03-01

    Isolations of genotype IX (gIX) avian paramyxovirus type 1 (APMV-1) from various bird species have been more common recently, with isolates showing variable pathogenicity in different species of poultry. Here we sequenced the genome of a Muscovy duck origin gIX virus strain XBT14 and characterized the virulence and pathogenicity of this isolate in chickens and ducks. The genome sequence of strain XBT14 is 15,192 nt in length, containing multiple basic amino acids at the fusion protein cleavage site. The XBT14 strain shared 91.6%-91.9% nucleotide identities with early-genotype viruses (such as genotype III and IV) and shared 85.3%-85.9% nucleotide homologies with later genotype viruses (such as genotype VII). Pathogenicity tests showed that strain XBT14 could cause death in different duck breeds with a mortality rate of 44.4% in Muscovy duck, 25.9% in Sheldrake, and 11.1% in Cherry Valley duck, respectively. Similar mortality discrepancies were also observed in different ducks when infected with chicken-origin gIX virus strain F48E8. These results indicate that XBT14-like velogenic gIX APMV-1 (such as XBT14, F48E8, and GD09-2) could cause fatal infection in duck, and genotype IX is another genotype velogenic to duck as well as genotype VII. Accompanied by genetic differences in the vaccine strains or dominant strains prevailing in poultry, the virulent XBT14-like gIX viruses might become potentially endemic strains in poultry in the future.

  14. Uptake and partitioning of zinc in Lemnaceae.

    PubMed

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility.

  15. Zinc: an essential but elusive nutrient123

    PubMed Central

    King, Janet C

    2011-01-01

    Zinc is essential for multiple aspects of metabolism. Physiologic signs of zinc depletion are linked with diverse biochemical functions rather than with a specific function, which makes it difficult to identify biomarkers of zinc nutrition. Nutrients, such as zinc, that are required for general metabolism are called type 2 nutrients. Protein and magnesium are examples of other type 2 nutrients. Type 1 nutrients are required for one or more specific functions: examples include iron, vitamin A, iodine, folate, and copper. When dietary zinc is insufficient, a marked reduction in endogenous zinc loss occurs immediately to conserve the nutrient. If zinc balance is not reestablished, other metabolic adjustments occur to mobilize zinc from small body pools. The location of those pools is not known, but all cells probably have a small zinc reserve that includes zinc bound to metallothionein or zinc stored in the Golgi or in other organelles. Plasma zinc is also part of this small zinc pool that is vulnerable to insufficient intakes. Plasma zinc concentrations decline rapidly with severe deficiencies and more moderately with marginal depletion. Unfortunately, plasma zinc concentrations also decrease with a number of conditions (eg, infection, trauma, stress, steroid use, after a meal) due to a metabolic redistribution of zinc from the plasma to the tissues. This redistribution confounds the interpretation of low plasma zinc concentrations. Biomarkers of metabolic zinc redistribution are needed to determine whether this redistribution is the cause of a low plasma zinc rather than poor nutrition. Measures of metallothionein or cellular zinc transporters may fulfill that role. PMID:21715515

  16. Understanding Noncompliance: A Qualitative Content Analysis of Title IX Sexual Misconduct Violations Using the Office for Civil Rights Investigative Findings

    ERIC Educational Resources Information Center

    Schaffer, Lenore

    2017-01-01

    On April 4, 2011, the U.S. Department of Education's Office for Civil Rights (OCR) released a Dear Colleague Letter (DCL) reminding higher education institutions (HEIs) of their obligations under Title IX to respond to complaints of sexual misconduct. The 2011 DCL was meant to be a guidance document to assist HEIs in complying with Title IX, but…

  17. Effect of short-term zinc supplementation on zinc and selenium tissue distribution and serum antioxidant enzymes.

    PubMed

    Skalny, Andrey A; Tinkov, Alexey A; Medvedeva, Yulia S; Alchinova, Irina B; Karganov, Mikhail Y; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    A significant association between Zn and Se homeostasis exists. At the same time, data on the influence of zinc supplementation on selenium distribution in organs and tissues seem to be absent. Therefore, the primary objective of the current study is to investigate the influence of zinc asparaginate supplementation on zinc and selenium distribution and serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in Wistar rats. 36 rats were used in the experiment. The duration of the experiment was 7 and 14 days in the first and second series, respectively. The rats in Group I were used as the control ones. Animals in Groups II and III daily obtained zinc asparaginate (ZnA) in the doses of 5 and 15 mg/kg weight, respectively. Zinc and selenium content in liver, kidneys, heart, muscle, serum and hair was assessed using inductively coupled plasma mass spectrometry. Serum SOD and GPx activity was analysed spectrophotometrically using Randox kits. Intragastric administration of zinc asparaginate significantly increased liver, kidney, and serum zinc content without affecting skeletal and cardiac muscle levels. Zinc supplementation also stimulated selenium retention in the rats' organs. Moreover, a significant positive correlation between zinc and selenium content was observed. Finally, zinc asparaginate treatment has been shown to modulate serum GPx but not SOD activity. The obtained data indicate that zinc-induced increase in GPx activity may be mediated through modulation of selenium status. However, future studies are required to estimate the exact mechanisms of zinc and selenium interplay.

  18. Zinc oxide overdose

    MedlinePlus

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  19. Selective Acidic Leaching of Spent Zinc-Carbon Batteries Followed by Zinc Electrowinning

    NASA Astrophysics Data System (ADS)

    Shalchian, Hossein; Rafsanjani-Abbasi, Ali; Vahdati-Khaki, Jalil; Babakhani, Abolfazl

    2015-02-01

    In this work, a selective acidic leaching procedure was employed for recycling zinc from spent zinc-carbon batteries. Leaching experiments were carried out in order to maximize zinc recovery and minimize manganese recovery in diluted sulfuric acid media. Response surface methodology and analysis of variance were employed for experimental design, data analysis, and leaching optimization. The experimental design has 28 experiments that include 24 main runs and four replicate in center point. The optimal conditions obtained from the selective acidic leaching experiments, were sulfuric acid concentration of 1 pct v/v, leaching temperature of 343 K (70 °C), pulp density of 8 pct w/v, and stirring speed of 300 rpm. The results show that the zinc and manganese recoveries after staged selective leaching are about 92 and 15 pct, respectively. Finally, metallic zinc with purity of 99.9 pct and electrolytic manganese dioxide were obtained by electrowinning.

  20. Bioavailability of Zinc in Wistar Rats Fed with Rice Fortified with Zinc Oxide

    PubMed Central

    Della Lucia, Ceres Mattos; Santos, Laura Luiza Menezes; Rodrigues, Kellen Cristina da Cruz; Rodrigues, Vivian Cristina da Cruz; Martino, Hércia Stampini Duarte; Pinheiro Sant’Ana, Helena Maria

    2014-01-01

    The study of zinc bioavailability in foods is important because this mineral intake does not meet the recommended doses for some population groups. Also, the presence of dietary factors that reduce zinc absorption contributes to its deficiency. Rice fortified with micronutrients (Ultra Rice®) is a viable alternative for fortification since this cereal is already inserted into the population habit. The aim of this study was to evaluate the bioavailability of zinc (Zn) in rice fortified with zinc oxide. During 42 days, rats were divided into four groups and fed with diets containing two different sources of Zn (test diet: UR® fortified with zinc oxide, or control diet: zinc carbonate (ZnCO3)), supplying 50% or 100%, respectively, of the recommendations of this mineral for animals. Weight gain, food intake, feed efficiency ratio, weight, thickness and length of femur; retention of zinc, calcium (Ca) and magnesium (Mg) in the femur and the concentrations of Zn in femur, plasma and erythrocytes were evaluated. Control diet showed higher weight gain, feed efficiency ratio, retention of Zn and Zn concentration in the femur (p < 0.05). However, no differences were observed (p > 0.05) for dietary intake, length and thickness of the femur, erythrocyte and plasmatic Zn between groups. Although rice fortified with zinc oxide showed a lower bioavailability compared to ZnCO3, this food can be a viable alternative to be used as a vehicle for fortification. PMID:24932657

  1. Zinc finger proteins in cancer progression.

    PubMed

    Jen, Jayu; Wang, Yi-Ching

    2016-07-13

    Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.

  2. Systemic delivery of factor IX messenger RNA for protein replacement therapy

    PubMed Central

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

    2017-01-01

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

  3. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  4. Selection and maturation of antibodies by phage display through fusion to pIX.

    PubMed

    Tornetta, Mark; Reddy, Ramachandra; Wheeler, John C

    2012-09-01

    Antibody discovery and optimization by M13 phage display have evolved significantly over the past twenty years. Multiple methods of antibody display and selection have been developed - direct display on pIII or indirect display through a Cysteine disulfide linkage or a coiled-coil adapter protein. Here we describe display of Fab libraries on the smaller pIX protein at the opposite end of the virion and its application to discovery of novel antibodies from naive libraries. Antibody selection based on pIX-mediated display produces results comparable to other in vitro methods and uses an efficient direct infection of antigen-bound phages, eliminating any chemical dissociation step(s). Additionally, some evidence suggests that pIX-mediated display can be more efficient than pIII-mediated display in affinity selections. Functional assessment of phage-derived antibodies can be hindered by insufficient affinities or lack of epitopic diversity. Here we describe an approach to managing primary hits from our Fab phage libraries into epitope bins and subsequent high-throughput maturation of clones to isolate epitope- and sequence-diverse panels of high affinity binders. Use of the Octet biosensor was done to examine Fab binding in a facile label-free method and determine epitope competition groups. A receptor extracellular domain and chemokine were subjected to this method of binning and affinity maturation. Parental clones demonstrated improvement in affinity from 1-100nM to 10-500pM. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Effect of zinc gluconate, sage oil on inflammatory patterns and hyperglycemia in zinc deficient diabetic rats.

    PubMed

    Elseweidy, Mohamed M; Ali, Abdel-Moniem A; Elabidine, Nabila Zein; Mursey, Nada M

    2017-11-01

    The relationship between zinc homeostasis and pancreatic function had been established. In this study we aimed firstly to configure the inflammatory pattern and hyperglycemia in zinc deficient diabetic rats. Secondly to illustrate the effect of two selected agents namely Zinc gluconate and sage oil (Salvia Officinalis, family Lamiaceae). Rats were fed on Zinc deficient diet, deionized water for 28days along with Zinc level check up at intervals to achieve zinc deficient state then rats were rendered diabetic through receiving one dose of alloxan monohydrate (120mg/kg) body weight, classified later into 5 subgroups. Treatment with sage oil (0.042mg/kg IP) and Zinc gluconate orally (150mg/kg) body weight daily for 8 weeks significantly reduced serum glucose, C-reactive protein (CRP), Tumor necrosis factor alpha (TNF- α), interleukins-6 1 β, inflammatory8 (IFN ȣ), pancreatic 1L1-β along with an increase in serum Zinc and pancreatic Zinc transporter 8 (ZNT8). Histopathological results of pancreatic tissues showed a good correlation with the biochemical findings. Both sage oil and zinc gluconate induced an improvement in the glycemic and inflammatory states. This may be of value like the therapeutic agent for diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer

    PubMed Central

    Franklin, Renty B; Feng, Pei; Milon, B; Desouki, Mohamed M; Singh, Keshav K; Kajdacsy-Balla, André; Bagasra, Omar; Costello, Leslie C

    2005-01-01

    Background The genetic and molecular mechanisms responsible for and associated with the development and progression of prostate malignancy are largely unidentified. The peripheral zone is the major region of the human prostate gland where malignancy develops. The normal peripheral zone glandular epithelium has the unique function of accumulating high levels of zinc. In contrast, the ability to accumulate zinc is lost in the malignant cells. The lost ability of the neoplastic epithelial cells to accumulate zinc is a consistent factor in their development of malignancy. Recent studies identified ZIP1 (SLC39A1) as an important zinc transporter involved in zinc accumulation in prostate cells. Therefore, we investigated the possibility that down-regulation of hZIP1 gene expression might be involved in the inability of malignant prostate cells to accumulate zinc. To address this issue, the expression of hZIP1 and the depletion of zinc in malignant versus non-malignant prostate glands of prostate cancer tissue sections were analyzed. hZIP1 expression was also determined in malignant prostate cell lines. Results hZIP1 gene expression, ZIP1 transporter protein, and cellular zinc were prominent in normal peripheral zone glandular epithelium and in benign hyperplastic glands (also zinc accumulating glands). In contrast, hZIP1 gene expression and transporter protein were markedly down-regulated and zinc was depleted in adenocarcinomatous glands and in prostate intra-epithelial neoplastic foci (PIN). These changes occur early in malignancy and are sustained during its progression in the peripheral zone. hZIP1 is also expressed in the malignant cell lines LNCaP, PC-3, DU-145; and in the nonmalignant cell lines HPr-1 and BPH-1. Conclusion The studies clearly establish that hZIP1 gene expression is down regulated and zinc is depleted in adenocarcinomatous glands. The fact that all the malignant cell lines express hZIP1 indicates that the down-regulation in adenocarcinomatous

  7. OATYC Journal, Vol. IX, Nos. 1-2, Autumn 1983-Spring 1984.

    ERIC Educational Resources Information Center

    Fullen, James, Ed.

    1984-01-01

    "OATYC Journal," which is published by the Ohio Association of Two-Year Colleges, is designed as a forum for the exchange of concepts, methods, and findings relevant to the two-year college classroom. Along with commentaries and letters of reaction from the readership, the two issues of volume IX present the following major articles: (1)…

  8. 5-ALA/PpIX fluorescence detection of gastrointestinal neoplasia

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina G.; Vladimirov, Borislav; Terziev, Ivan; Ivanova, Radina; Avramov, Latchezar

    2009-07-01

    In the recent study delta-ALA/PpIX is used as fluorescent marker for dysplasia and tumor detection in esophagus, stomach and colon. ALA is administered per os six to eight (depending on the lesion location) hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for the LED to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to re-absorption of oxy-hemoglobin in this spectral area. Endogenous and exogenous fluorescence spectra are used to develop simple but effective algorithm, based on dimensionless ratio of the signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues. Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  9. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  10. MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

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

    Detappe, A; Institut Lumiere-Matiere, Villeurbanne; Nano-H, St-Quentin Fallavier

    2015-06-15

    Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM ofmore » nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.« less

  11. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    NASA Astrophysics Data System (ADS)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  12. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

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

    Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.

    2014-12-15

    Fertilization of a mammalian egg initiates a series of 'zinc sparks' that are necessary to induce the egg-to-embryo transition. Despite the importance of these zinc-efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches that resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy-dispersive spectroscopy, X-ray fluorescence microscopy and three-dimensional elemental tomography for high-resolution elemental mapping. We show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each ofmore » which contains, on average, 10(6) zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. The discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes« less

  13. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks.

    PubMed

    Que, Emily L; Bleher, Reiner; Duncan, Francesca E; Kong, Betty Y; Gleber, Sophie C; Vogt, Stefan; Chen, Si; Garwin, Seth A; Bayer, Amanda R; Dravid, Vinayak P; Woodruff, Teresa K; O'Halloran, Thomas V

    2015-02-01

    Fertilization of a mammalian egg initiates a series of 'zinc sparks' that are necessary to induce the egg-to-embryo transition. Despite the importance of these zinc-efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches that resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy-dispersive spectroscopy, X-ray fluorescence microscopy and three-dimensional elemental tomography for high-resolution elemental mapping. We show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 10(6) zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. The discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes.

  14. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

    DOE PAGES

    Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.; ...

    2014-12-15

    Fertilization of a mammalian egg induces a series of ‘zinc sparks’ that are necessary for inducing the egg-to-embryo transition. Despite the importance of these zinc efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches to resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy dispersive spectroscopy, X-ray fluorescence microscopy, and 3D elemental tomography for high resolution elemental mapping. Here we show that the zinc spark arises from a system of thousands ofmore » zinc-loaded vesicles, each of which contains, on average, 106 zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. We conclude that the discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes.« less

  15. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

    PubMed Central

    Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.; Kong, Betty Y.; Gleber, Sophie C.; Vogt, Stefan; Chen, Si; Garwin, Seth A.; Bayer, Amanda R.; Dravid, Vinayak; Woodruff, Teresa K.; O’Halloran, Thomas V.

    2015-01-01

    Fertilization of a mammalian egg induces a series of ‘zinc sparks’ that are necessary for inducing the egg-to-embryo transition. Despite the importance of these zinc efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches to resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy dispersive spectroscopy, X-ray fluorescence microscopy, and 3D elemental tomography for high resolution elemental mapping. We show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 106 zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. The discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes. PMID:25615666

  16. Perceptions of Title IX Administrators in Arkansas Institutions of Higher Education on Implementing Office for Civil Rights Guidance: A Qualitative Study

    ERIC Educational Resources Information Center

    Jones, Arch

    2017-01-01

    With the significant pressure placed on higher education administrators, and more specifically Title IX Coordinators, to manage compliance of the Office for Civil Rights (OCR) guidance on Title IX, this study has focused on the perceptions of the of individuals tasked with this obligation. To determine from the individuals on the front line of…

  17. Ares I-X Range Safety Analyses Overview

    NASA Technical Reports Server (NTRS)

    Starr, Brett R.; Gowan, John W., Jr.; Thompson, Brian G.; Tarpley, Ashley W.

    2011-01-01

    Ares I-X was the first test flight of NASA's Constellation Program's Ares I Crew Launch Vehicle designed to provide manned access to low Earth orbit. As a one-time test flight, the Air Force's 45th Space Wing required a series of Range Safety analysis data products to be developed for the specified launch date and mission trajectory prior to granting flight approval on the Eastern Range. The range safety data package is required to ensure that the public, launch area, and launch complex personnel and resources are provided with an acceptable level of safety and that all aspects of prelaunch and launch operations adhere to applicable public laws. The analysis data products, defined in the Air Force Space Command Manual 91-710, Volume 2, consisted of a nominal trajectory, three sigma trajectory envelopes, stage impact footprints, acoustic intensity contours, trajectory turn angles resulting from potential vehicle malfunctions (including flight software failures), characterization of potential debris, and debris impact footprints. These data products were developed under the auspices of the Constellation's Program Launch Constellation Range Safety Panel and its Range Safety Trajectory Working Group with the intent of beginning the framework for the operational vehicle data products and providing programmatic review and oversight. A multi-center NASA team in conjunction with the 45th Space Wing, collaborated within the Trajectory Working Group forum to define the data product development processes, performed the analyses necessary to generate the data products, and performed independent verification and validation of the data products. This paper outlines the Range Safety data requirements and provides an overview of the processes established to develop both the data products and the individual analyses used to develop the data products, and it summarizes the results of the analyses required for the Ares I-X launch.

  18. Zinc in Infection and Inflammation.

    PubMed

    Gammoh, Nour Zahi; Rink, Lothar

    2017-06-17

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

  19. The zinc paradigm for metalloneurochemistry.

    PubMed

    Barr, Chelsea A; Burdette, Shawn C

    2017-05-09

    Neurotransmission and sensory perception are shaped through metal ion-protein interactions in various brain regions. The term "metalloneurochemistry" defines the unique field of bioinorganic chemistry focusing on these processes, and zinc has been the leading target of metalloneurochemists in the almost 15 years since the definition was introduced. Zinc in the hippocampus interacts with receptors that dictate ion flow and neurotransmitter release. Understanding the intricacies of these interactions is crucial to uncovering the role that zinc plays in learning and memory. Based on receptor similarities and zinc-enriched neurons (ZENs) in areas of the brain responsible for sensory perception, such as the olfactory bulb (OB), and dorsal cochlear nucleus (DCN), zinc participates in odor and sound perception. Development and improvement of methods which allow for precise detection and immediate manipulation of zinc ions in neuronal cells and in brain slices will be critical in uncovering the synaptic action of zinc and, more broadly, the bioinorganic chemistry of cognition. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. High-resolution Laboratory Measurements of Coronal Lines near the Fe IX Line at 171 Å

    NASA Astrophysics Data System (ADS)

    Beiersdorfer, Peter; Träbert, Elmar

    2018-02-01

    We present high-resolution laboratory measurements in the spectral region between 165 and 175 Å that focus on the emission from various ions of C, O, F, Ne, S, Ar, Fe, and Ni. This wavelength region is centered on the λ171 Fe IX channel of the Atmospheric Imaging Assembly on the Solar Dynamics Observatory, and we place special emphasis on the weaker emission lines of Fe IX predicted in this region. In general, our measurements show a multitude of weak lines missing in the current databases, where the emission lines of Ni are probably most in need of further identification and reclassification. We also find that the wavelengths of some of the known lines need updating. Using the multi-reference Møller–Plesset method for wavelength predictions and collisional-radiative modeling of the line intensities, we have made tentative assignments of more than a dozen lines to the spectrum of Fe IX, some of which have formerly been identified as Fe VII, Fe XIV, or Fe XVI lines. Several Fe features remain unassigned, although they appear to be either Fe VII or Fe X lines. Further work will be needed to complete and correct the spectral line lists in this wavelength region.

  1. Mineral resource of the month: zinc

    USGS Publications Warehouse

    Tolcin, Amy C.

    2009-01-01

    The article provides information on zinc, the fourth most-widely consumed metal. It traces the first use of zinc with the Romans' production of brass. It describes the presence of zinc in Earth's crust and the importance of sphalerite as a source of zinc and other some minor metal production. The production and consumption of zinc as well as the commercial and industrial uses of this metal are also discussed.

  2. Zinc Therapy in Dermatology: A Review

    PubMed Central

    Mahajan, Vikram K.; Mehta, Karaninder S.; Chauhan, Pushpinder S.

    2014-01-01

    Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc. PMID:25120566

  3. Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

    PubMed

    Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

    2018-01-24

    Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

  4. Possible role of zinc in diminishing lead-related occupational stress-a zinc nutrition concern.

    PubMed

    Wani, Ab Latif; Ahmad, Ajaz; Shadab, G G H A; Usmani, Jawed Ahmad

    2017-03-01

    Lead and zinc are mostly present at the same occupational source and usually found as co-contaminants. Lead is known to associate with detrimental effects to humans. Zinc however is an essential nutrient and its deficiency causes debilitating effects on growth and development. Besides, it acts as core ion of important enzymes and proteins. The purpose of this study was to examine if zinc concentrations are associated with blood lead levels and if zinc may prevent lead-induced DNA damage. Blood samples were collected from 92 workers as participants occupationally exposed to lead or lead and zinc and 38 comparison participants having no history of such exposure. Lead and zinc levels were determined from blood by atomic absorption spectrophotometry and genetic damage was assessed by comet assay. Correlation was calculated by Spearman's rho. Lead concentrations were observed to increase among workers with increase in years of exposure. There was a significant difference (p < 0.001) in blood lead levels between workers and controls. In addition, significant difference (p < 0.001) in the genetic damage was observed among workers and controls. A clear effect of increased occupational exposure was visible among workers. Multiple regression analysis further reveals the positive effect of lead, while as the inverse effect of zinc on DNA damage. The results suggest that zinc may influence body lead absorption and may have a role in preventing the genetic damage caused by lead.

  5. Effects of dietary supplementation with tribasic zinc sulfate or zinc sulfate on growth performance, zinc content and expression of zinc transporters in young pigs.

    PubMed

    Deng, Bo; Zhou, Xihong; Wu, Jie; Long, Ciming; Yao, Yajun; Peng, Hongxing; Wan, Dan; Wu, Xin

    2017-10-01

    An experiment was conducted to compare the effects of zinc sulfate (ZS) and tribasic zinc sulfate (TBZ) as sources of supplemental zinc on growth performance, serum zinc (Zn) content and messenger RNA (mRNA) expression of Zn transporters (ZnT1/ZnT2/ZnT5/ZIP4/DMT1) of young growing pigs. A total of 96 Duroc × Landrace × Yorkshire pigs were randomly allotted to two treatments and were fed a basal diet supplemented with 100 mg/kg Zn from either ZS or TBZ for 28 days. Feed : gain ratio in pigs fed TBZ were lower (P < 0.05) than pigs fed ZS, and average daily weight gain tended to increase (0.05 ≤ P ≤ 0.10) in pigs fed TBZ. Compared with pigs fed ZS, pigs fed TBZ had a higher CuZn-superoxide dismutase and Zn content in serum (P < 0.05) while they had a lower Zn content in feces (P < 0.05). In addition, ZIP4 mRNA expression of zinc transporter in either duodenum or jejunum of pigs fed TBZ were higher (P < 0.05) than pigs fed ZS. These results indicate that TBZ is more effective in serum Zn accumulation and intestinal Zn absorption, and might be a potential substitute for ZS in young growing pigs. © 2017 Japanese Society of Animal Science.

  6. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach.

    PubMed

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; Van Dorsselaer, Alain; Rabilloud, Thierry

    2014-06-07

    Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.

  7. Recovering Zinc From Discarded Tires

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1984-01-01

    Zinc sulfate monohydrate sold at profit. Shredded tire material steeped in three sulfuric acid baths to extract zinc. Final product removed by evaporating part of solution until product crystallizes out. Recovered as zinc sulfate monohydrate and sold as fertilizer or for general use.

  8. Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B.

    PubMed

    Cao, Ou; Hoffman, Brad E; Moghimi, Babak; Nayak, Sushrusha; Cooper, Mario; Zhou, Shangzhen; Ertl, Hildegund C J; High, Katherine A; Herzog, Roland W

    2009-10-01

    Immune responses to factor IX (F.IX), a major concern in gene therapy for hemophilia, were analyzed for adeno-associated viral (AAV-2) gene transfer to skeletal muscle and liver as a function of the F9 underlying mutation. Vectors identical to those recently used in clinical trials were administered to four lines of hemophilia B mice on a defined genetic background [C3H/HeJ with deletion of endogenous F9 and transgenic for a range of nonfunctional human F.IX (hF.IX) variants]. The strength of the immune response to AAV-encoded F.IX inversely correlated with the degree of conservation of endogenous coding information and levels of endogenous antigen. Null mutation animals developed T- and B-cell responses in both protocols. However, inhibitor titers were considerably higher upon muscle gene transfer (or protein therapy). Transduced muscles of Null mice had strong infiltrates with CD8+ cells, which were much more limited in the liver and not seen for the other mutations. Sustained expression was achieved with liver transduction in mice with crm(-) nonsense and missense mutations, although they still formed antibodies upon muscle gene transfer. Therefore, endogenous expression prevented T-cell responses more effectively than antibody formation, and immune responses varied substantially depending on the protocol and the underlying mutation.

  9. Zinc Signal in Brain Diseases.

    PubMed

    Portbury, Stuart D; Adlard, Paul A

    2017-11-23

    The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer's disease or negative outcomes following brain injury.

  10. Zinc in Entamoeba invadens.

    NASA Technical Reports Server (NTRS)

    Morgan, R. S.; Sattilaro, R. F.

    1972-01-01

    Atomic absorption spectroscopy, electron microprobe analysis, and dithizone staining of trophozoites and cysts of Entamoeba invadens demonstrate that these cells have a high concentration of zinc (approximately one picogram per cell or 1% of their dry weight). In the cysts of this organism, the zinc is confined to the chromatoid bodies, which previous work has shown to contain crystals of ribosomes. The chemical state and function of this zinc are unknown.

  11. Comparison of Ares I-X Wind-Tunnel Derived Buffet Environment with Flight Data

    NASA Technical Reports Server (NTRS)

    Piatak, David J.; Sekula, Martin K.; Rausch, Russ D.

    2011-01-01

    The Ares I-X Flight Test Vehicle (FTV), launched in October 2009, carried with it over 243 buffet verification pressure sensors and was one of the most heavily instrumented launch vehicle flight tests. This flight test represented a unique opportunity for NASA and its partners to compare the wind-tunnel derived buffet environment with that measured during the flight of Ares I-X. It is necessary to define the launch vehicle buffet loads to ensure that structural components and vehicle subsystems possess adequate strength, stress, and fatigue margins when the vehicle structural dynamic response to buffet forcing functions are considered. Ares I-X buffet forcing functions were obtained via wind-tunnel testing of a rigid buffet model (RBM) instrumented with hundreds of unsteady pressure transducers designed to measure the buffet environment across the desired frequency range. This paper discusses the comparison of RBM and FTV buffet environments, including fluctuating pressure coefficient and normalized sectional buffet forcing function root-mean-square magnitudes, frequency content of power-spectral density functions, and force magnitudes of an alternating flow phenomena. Comparison of wind-tunnel model and flight test vehicle buffet environments show very good agreement with root-mean-square magnitudes of buffet forcing functions at the majority of vehicle stations. Spectra proved a challenge to compare because of different wind-tunnel and flight test conditions and data acquisition rates. However, meaningful and promising comparisons of buffet spectra are presented. Lastly, the buffet loads resulting from the transition of subsonic separated flow to supersonic attached flow were significantly over-predicted by wind-tunnel results.

  12. A Photoluminescence Study of the Changes Induced in the Zinc White Pigment by Formation of Zinc Complexes

    PubMed Central

    Artesani, Alessia; Gherardi, Francesca; Nevin, Austin; Valentini, Gianluca; Comelli, Daniela

    2017-01-01

    It is known that oil paintings containing zinc white are subject to rapid degradation. This is caused by the interaction between the active groups of binder and the metal ions of the pigment, which gives rise to the formation of new zinc complexes (metal soaps). Ongoing studies on zinc white paints have been limited to the chemical mechanisms that lead to the formation of zinc complexes. On the contrary, little is known of the photo-physical changes induced in the zinc oxide crystal structure following this interaction. Time-resolved photoluminescence spectroscopy has been applied to follow modifications in the luminescent zinc white pigment when mixed with binder. Significant changes in trap state photoluminescence emissions have been detected: the enhancement of a blue emission combined with a change of the decay kinetic of the well-known green emission. Complementary data from molecular analysis of paints using Fourier transform infrared spectroscopy confirms the formation of zinc carboxylates and corroborates the mechanism for zinc complexes formation. We support the hypothesis that zinc ions migrate into binder creating novel vacancies, affecting the photoluminescence intensity and lifetime properties of zinc oxide. Here, we further demonstrate the advantages of a time-resolved photoluminescence approach for studying defects in semiconductor pigments. PMID:28772700

  13. Induced Protoporphyrin IX Accumulation by the δ-Aminolevulinic Acid in Bacteria and its Potential Use in the Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Brígido-Aparicio, Cyntiha; Ramón-Gallegos, Eva; Arenas-Huertero, Francisco Jesús; Uribe-Hernández, Raúl

    2008-08-01

    The increasing incident of resistant strains to antibiotic has encouraged the search of new antibacterial treatments, such as the photodynamic therapy. In recent years, photodynamic therapy has demonstrated being a good technology for the treatment of recurrent bacteria infection. PDT presents a hopeful approach to eliminate Gram positive and negative bacteria in immunological compromised patients. This therapy uses a laser in combination with a photosensibilizer in presence of intracellular molecular oxygen. The process generates an effect of phototoxicity in bacterial cells. The aim of this work was to determine the in vitro conditions to accumulate PpIX in effective concentrations in Staphylococcus aureus ATCC25923 and Streptococcus pyogenes, which are responsible of human cutaneous diseases. A cellular suspension of both strains was prepared in TSB to obtain growth in Log-phase, then, the suspensions were adjusted to a final concentration of 2.61×108 cells/mL. The strains were exposed to increasing concentrations from 0 to 160μg/mL of δ-ALA in order to determinate the concentration that induces the biggest accumulation of PpIX. PpIX was measured using the Piomelli method modified for bacteria. The concentration selected was 40 mg/mL of ALA. It was found that in basal concentration of δ-ALA (0 μg/mL) both strains accumulated similar amount of PpIX. In concentrations of 5 mg/mL of δ-ALA it was observed a significant (p<0.001) increment in PpIX concentration. Finally it was realized a kinetic to determinate the optimal accumulation over the time at 0, 5, 10, 15 and 30 min, and 1, 2, 4, 8, 16 and 32 h. It was found that the ideal time for PDT application, in both strains, was 24 h because in smaller times there was not statistically significant difference. The S. aureus ATCC25923 accumulated significantly the biggest concentration of PpIX with regard to S. pyogenes. In conclusion, it was found that the optimal conditions to apply PDT will be to expose both

  14. Zinc in Infection and Inflammation

    PubMed Central

    Gammoh, Nour Zahi; Rink, Lothar

    2017-01-01

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli. PMID:28629136

  15. Detection limits of 405 nm and 633 nm excited PpIX fluorescence for brain tumor detection during stereotactic biopsy

    NASA Astrophysics Data System (ADS)

    Markwardt, Niklas; Götz, Marcus; Haj-Hosseini, Neda; Hollnburger, Bastian; Sroka, Ronald; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

    2016-04-01

    5-aminolevulinic-acid-(5-ALA)-induced protoporphyrin IX (PpIX) fluorescence may be used to improve stereotactic brain tumor biopsies. In this study, the sensitivity of PpIX-based tumor detection has been investigated for two potential excitation wavelengths (405 nm, 633 nm). Using a 200 μm fiber in contact with semi-infinite optical phantoms containing ink and Lipovenös, PpIX detection limits of 4.0 nM and 200 nM (relating to 1 mW excitation power) were determined for 405 nm and 633 nm excitation, respectively. Hence, typical PpIX concentrations in glioblastomas of a few μM should be well detectable with both wavelengths. Additionally, blood layers of selected thicknesses were placed between fiber and phantom. Red excitation was shown to be considerably less affected by blood interference: A 50 μm blood layer, for instance, blocked the 405- nm-excited fluorescence completely, but reduced the 633-nm-excited signal by less than 50%. Ray tracing simulations demonstrated that - without blood layer - the sensitivity advantage of 405 nm rises for decreasing fluorescent volume from 50-fold to a maximum of 100-fold. However, at a tumor volume of 1 mm3, which is a typical biopsy sample size, the 633-nm-excited fluorescence signal is only reduced by about 10%. Further simulations revealed that with increasing fiber-tumor distance, the signal drops faster for 405 nm. This reduces the risk of detecting tumor tissue outside the needle's coverage, but diminishes the overlap between optically and mechanically sampled volumes. While 405 nm generally offers a higher sensitivity, 633 nm is more sensitive to distant tumors and considerably superior in case of blood-covered tumor tissue.

  16. A concentrated electrolyte for zinc hexacyanoferrate electrodes in aqueous rechargeable zinc-ion batteries

    NASA Astrophysics Data System (ADS)

    Kim, D.; Lee, C.; Jeong, S.

    2018-01-01

    In this study, a concentrated electrolyte was applied in an aqueous rechargeable zinc-ion battery system with a zinc hexacyanoferrate (ZnHCF) electrode to improve the electrochemical performance by changing the hydration number of the zinc ions. To optimize the active material, ZnHCF was synthesized using aqueous solutions of zinc nitrate with three different concentrations. The synthesized materials exhibited some differences in structure, crystallinity, and particle size, as observed by X-ray diffraction and scanning electron microscopy. Subsequently, these well-structured materials were applied in electrochemical tests. A more than two-fold improvement in the charge/discharge capacities was observed when the concentrated electrolyte was used instead of the dilute electrolyte. Additionally, the cycling performance observed in the concentrated electrolyte was superior to that in the dilute electrolyte. This improvement in the electrochemical performance may result from a decrease in the hydration number of the zinc ions in the concentrated electrolyte.

  17. New Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A Streptococcal Infection.

    PubMed

    Ong, Cheryl-Lynn Y; Berking, Olga; Walker, Mark J; McEwan, Alastair G

    2018-06-01

    Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation ("nutritional immunity") to combat infections. Here, we investigate the role of zinc import and export in the protection of Streptococcus pyogenes (group A Streptococcus ; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defense. In order to determine the role of GAS zinc import and export during infection, we utilized zinc import (Δ adcA Δ adcAII ) and export (Δ czcD ) deletion mutants in competition with the wild type in both in vitro and in vivo virulence models. We demonstrate that nutritional immunity is deployed extracellularly, while zinc toxicity is utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and azurophilic granules in neutrophils contain zinc stores for use against intracellular pathogens. Copyright © 2018 American Society for Microbiology.

  18. Particulate nanocomposite from oyster (Crassostrea rivularis) hydrolysates via zinc chelation improves zinc solubility and peptide activity.

    PubMed

    Zhang, Ziran; Zhou, Feibai; Liu, Xiaoling; Zhao, Mouming

    2018-08-30

    An oyster protein hydrolysates-zinc complex (OPH-Zn) was prepared and investigated to improve zinc bioaccessibility. Zinc ions chelating with oyster protein hydrolysates (OPH) cause intramolecular and intermolecular folding and aggregation, homogeneously forming the OPH-Zn complex as nanoclusters with a Z-average at 89.28 nm (PDI: 0.16 ± 0.02). The primary sites of zinc-binding in OPH were carboxyl groups, carbonyl groups, and amino groups, and they were related to the high number of charged amino acid residues. Furthermore, formation of the OPH-Zn complex could significantly enhance zinc solubility both under specific pH conditions as well as during simulated gastrointestinal digestion, compared to the commonly used ZnSO 4 . Additionally, after digestion, either preserved or enhanced antioxidant activity of OPH was found when chelated with zinc. These results indicated that the OPH-Zn complex could be a potential functional ingredient with improved antioxidant bioactivity and zinc bioaccessibility. Copyright © 2018. Published by Elsevier Ltd.

  19. Zinc-mediated Allosteric Inhibition of Caspase-6*

    PubMed Central

    Velázquez-Delgado, Elih M.; Hardy, Jeanne A.

    2012-01-01

    Zinc and caspase-6 have independently been implicated in several neurodegenerative disorders. Depletion of zinc intracellularly leads to apoptosis by an unknown mechanism. Zinc inhibits cysteine proteases, including the apoptotic caspases, leading to the hypothesis that zinc-mediated inhibition of caspase-6 might contribute to its regulation in a neurodegenerative context. Using inductively coupled plasma optical emission spectroscopy, we observed that caspase-6 binds one zinc per monomer, under the same conditions where the zinc leads to complete loss of enzymatic activity. To understand the molecular details of zinc binding and inhibition, we performed an anomalous diffraction experiment above the zinc edge. The anomalous difference maps showed strong 5σ peaks, indicating the presence of one zinc/monomer bound at an exosite distal from the active site. Zinc was not observed bound to the active site. The zinc in the exosite was liganded by Lys-36, Glu-244, and His-287 with a water molecule serving as the fourth ligand, forming a distorted tetrahedral ligation sphere. This exosite appears to be unique to caspase-6, as the residues involved in zinc binding were not conserved across the caspase family. Our data suggest that binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation. PMID:22891250

  20. The biological inorganic chemistry of zinc ions.

    PubMed

    Krężel, Artur; Maret, Wolfgang

    2016-12-01

    The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the "mobile" zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn 2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn 2+ differs from s-block cations such as Ca 2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is

  1. Generic absence of strong singularities in loop quantum Bianchi-IX spacetimes

    NASA Astrophysics Data System (ADS)

    Saini, Sahil; Singh, Parampreet

    2018-03-01

    We study the generic resolution of strong singularities in loop quantized effective Bianchi-IX spacetime in two different quantizations—the connection operator based ‘A’ quantization and the extrinsic curvature based ‘K’ quantization. We show that in the effective spacetime description with arbitrary matter content, it is necessary to include inverse triad corrections to resolve all the strong singularities in the ‘A’ quantization. Whereas in the ‘K’ quantization these results can be obtained without including inverse triad corrections. Under these conditions, the energy density, expansion and shear scalars for both of the quantization prescriptions are bounded. Notably, both the quantizations can result in potentially curvature divergent events if matter content allows divergences in the partial derivatives of the energy density with respect to the triad variables at a finite energy density. Such events are found to be weak curvature singularities beyond which geodesics can be extended in the effective spacetime. Our results show that all potential strong curvature singularities of the classical theory are forbidden in Bianchi-IX spacetime in loop quantum cosmology and geodesic evolution never breaks down for such events.

  2. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  3. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  4. Noninvasive imaging of absolute PpIX concentration distribution in nonmelanoma skin tumors at pre-PDT

    NASA Astrophysics Data System (ADS)

    Sunar, Ulas; Rohrbach, Daniel; Morgan, Janet; Zeitouni, Natalie

    2013-03-01

    Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX (PpIX) in phantoms and in vivo. We correct fluorescence against the effects of native tissue absorption and scattering parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug concentration in vivo at pre-PDT.

  5. Longitudinal changes in zinc transport kinetics, metallothionein, and zinc transporter expression in a blood-brain barrier model in response to a moderately excessive zinc environment$

    PubMed Central

    Gauthier, Nicole A.; Karki, Shakun; Olley, Bryony J.; Thomas, W. Kelly

    2008-01-01

    A blood-brain barrier (BBB) model composed of porcine brain capillary endothelial cells (BCEC) was exposed to a moderately excessive zinc environment (50 µmol Zn/L) in cell culture and longitudinal measurements were made of zinc transport kinetics, ZnT-1 (SLC30A1) expression, and changes in the protein concentration of metallothionein (MT), ZnT-1, ZnT-2 (SLC30A2), and Zip1 (SLC39A1). Zinc release by cells of the BBB model was significantly increased after 12–24 h of exposure, but decreased back to control levels after 48–96 h, as indicated by transport across the BBB from both the ablumenal (brain) and lumenal (blood) directions. Expression of ZnT-1, the zinc export protein, increased 169% within 12 h, but was no longer different from controls after 24 h. Likewise, ZnT-1 protein content increased transiently after 12 h of exposure but returned to control levels by 24 h. Capacity for zinc uptake and retention increased from both the lumenal and ablumenal directions within 12–24 h of exposure and remained elevated. MT and ZnT-2 were elevated within 12 h and remained elevated throughout the study. Zip1 was unchanged by the treatment. The BBB’s response to a moderately high zinc environment was dynamic and involved multiple mechanisms. The initial response was to increase the cell’s capacity to sequester zinc with additional MT and increase zinc export with the ZnT-1 protein. But, the longer term strategy involved increasing ZnT-2 transporters, presumably to sequester zinc into intracellular vesicles as a mechanism to protect the brain and maintain brain zinc homeostasis. PMID:18061429

  6. Zinc-The key to preventing corrosion

    USGS Publications Warehouse

    Kropschot, S.J.; Doebrich, Jeff L.

    2011-01-01

    Centuries before it was identified as an element, zinc was used to make brass (an alloy of zinc and copper) and for medicinal purposes. Metallic zinc and zinc oxide were produced in India sometime between the 11th and 14th centuries and in China in the 17th century, although the discovery of pure metallic zinc is credited to the German chemist Andreas Marggraf, who isolated the element in 1746. Refined zinc metal is bluish-white when freshly cast; it is hard and brittle at most temperatures and has relatively low melting and boiling points. Zinc alloys readily with other metals and is chemically active. On exposure to air, it develops a thin gray oxide film (patina), which inhibits deeper oxidation (corrosion) of the metal. The metal's resistance to corrosion is an important characteristic in its use.

  7. Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

    DOEpatents

    Adler, Thomas C.; McLarnon, Frank R.; Cairns, Elton J.

    1995-01-01

    An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing one or more hydroxides having the formula M(OH), one or more fluorides having the formula MF, and one or more carbonates having the formula M.sub.2 CO.sub.3, where M is a metal selected from the group consisting of alkali metals. The electrolyte inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics.

  8. A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity.

    PubMed

    Richards, Christopher D; Warr, Coral G; Burke, Richard

    2017-01-01

    Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The Drosophila zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised Drosophila zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of Zip88E presented here indicates that Zip88E may instead play a role in detecting and responding to zinc toxicity. Larvae homozygous for a null Zip88E allele are viable yet display heightened sensitivity to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied by an overall decrease in Metallothionein B transcription throughout the larval midgut. A Zip88E reporter gene is expressed only in the salivary glands, a handful of enteroendocrine cells at the boundary between the anterior and middle midgut regions, and in two parallel strips of sensory cell projections connecting to the larval ventral ganglion. Zip88E expression solely in this restricted subset of cells is sufficient to rescue the Zip88E mutant phenotype. Together, our data suggest that Zip88E may be functioning in a small subset of cells to detect excessive zinc levels and induce a systemic response to reduce dietary zinc absorption and hence protect against toxicity.

  9. Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

    PubMed Central

    Méndez, Rosa O.; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B.; de la Barca, Ana M. Calderón; García, Hugo S.

    2014-01-01

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1. PMID:24922175

  10. Regeneration of zinc chloride hydrocracking catalyst

    DOEpatents

    Zielke, Clyde W.

    1979-01-01

    Improved rate of recovery of zinc values from the solids which are carried over by the effluent vapors from the oxidative vapor phase regeneration of spent zinc chloride catalyst is achieved by treatment of the solids with both hydrogen chloride and calcium chloride to selectively and rapidly recover the zinc values as zinc chloride.

  11. Medicago truncatula Zinc-Iron Permease6 provides zinc to rhizobia-infected nodule cells.

    PubMed

    Abreu, Isidro; Saéz, Ángela; Castro-Rodríguez, Rosario; Escudero, Viviana; Rodríguez-Haas, Benjamín; Senovilla, Marta; Larue, Camille; Grolimund, Daniel; Tejada-Jiménez, Manuel; Imperial, Juan; González-Guerrero, Manuel

    2017-11-01

    Zinc is a micronutrient required for symbiotic nitrogen fixation. It has been proposed that in model legume Medicago truncatula, zinc is delivered by the root vasculature into the nodule and released in the infection/differentiation zone. There, transporters must introduce this element into rhizobia-infected cells to metallate the apoproteins that use zinc as a cofactor. MtZIP6 (Medtr4g083570) is an M. truncatula Zinc-Iron Permease (ZIP) that is expressed only in roots and nodules, with the highest expression levels in the infection/differentiation zone. Immunolocalization studies indicate that it is located in the plasma membrane of nodule rhizobia-infected cells. Down-regulating MtZIP6 expression levels with RNAi does not result in any strong phenotype when plants are fed mineral nitrogen. However, these plants displayed severe growth defects when they depended on nitrogen fixed by their nodules, losing of 80% of their nitrogenase activity. The reduction of this activity was likely an indirect effect of zinc being retained in the infection/differentiation zone and not reaching the cytosol of rhizobia-infected cells. These data are consistent with a model in which MtZIP6 would be responsible for zinc uptake by rhizobia-infected nodule cells in the infection/differentiation zone. © 2017 John Wiley & Sons Ltd.

  12. Atomic Data and Spectral Line Intensities for Ca IX

    NASA Technical Reports Server (NTRS)

    Landi, E.; Bhatia, A. K.

    2012-01-01

    Electron impact collision strengths, energy levels, oscillator strengths and spontaneous radiative decay rates are calculated for Ca IX. We include in the calculations the 33 lowest configurations in the n = 3, 4, 5 complexes, corresponding to 283 fine structure levels in the 3l3l ', 3l4l'' and 3l4l''' configurations, where l,l' = s, p, d, l '' = s, p, d, f and l''' = s, p, d, f, g. Collision strengths are calculated at five incident energies for all transitions: 5.8, 13.6, 24.2, 38.6 and 57.9 Ry above the threshold of each transition. An additional energy, very close to the transition threshold, has been added, whose value is between 0.0055 Ry and 0.23 Ry depending on the levels involved. Calculations have been carried out using the Flexible Atomic Code and the distorted wave approximation. Excitation rate coefficients are calculated as a function of electron temperature by assuming a Maxwellian electron velocity distribution. Using the excitation rate coefficients and the radiative transition rates calculated in the present work, statistical equilibrium equations for level populations are solved at electron densities covering the 10(exp 8)-10(exp 14)/cubic cm range and at an electron temperature of log T(sub e)(K)=5.8, corresponding to the maximum abundance of Ca IX. Spectral line intensities are calculated, and their diagnostic relevance is discussed.

  13. Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

    PubMed Central

    Kanoni, Stavroula; Nettleton, Jennifer A.; Hivert, Marie-France; Ye, Zheng; van Rooij, Frank J.A.; Shungin, Dmitry; Sonestedt, Emily; Ngwa, Julius S.; Wojczynski, Mary K.; Lemaitre, Rozenn N.; Gustafsson, Stefan; Anderson, Jennifer S.; Tanaka, Toshiko; Hindy, George; Saylor, Georgia; Renstrom, Frida; Bennett, Amanda J.; van Duijn, Cornelia M.; Florez, Jose C.; Fox, Caroline S.; Hofman, Albert; Hoogeveen, Ron C.; Houston, Denise K.; Hu, Frank B.; Jacques, Paul F.; Johansson, Ingegerd; Lind, Lars; Liu, Yongmei; McKeown, Nicola; Ordovas, Jose; Pankow, James S.; Sijbrands, Eric J.G.; Syvänen, Ann-Christine; Uitterlinden, André G.; Yannakoulia, Mary; Zillikens, M. Carola; Wareham, Nick J.; Prokopenko, Inga; Bandinelli, Stefania; Forouhi, Nita G.; Cupples, L. Adrienne; Loos, Ruth J.; Hallmans, Goran; Dupuis, Josée; Langenberg, Claudia; Ferrucci, Luigi; Kritchevsky, Stephen B.; McCarthy, Mark I.; Ingelsson, Erik; Borecki, Ingrid B.; Witteman, Jacqueline C.M.; Orho-Melander, Marju; Siscovick, David S.; Meigs, James B.; Franks, Paul W.; Dedoussis, George V.

    2011-01-01

    OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: −0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: −0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels. PMID:21810599

  14. Electrochemical behavior of zinc particles with silica based coatings as anode material for zinc air batteries with improved discharge capacity

    NASA Astrophysics Data System (ADS)

    Schmid, M.; Willert-Porada, M.

    2017-05-01

    Silica coatings on zinc particles as anode material for alkaline zinc air batteries are expected to reduce early formation of irreversible ZnO passivation layers during discharge by controlling zinc dissolution and precipitation of supersaturated zincates, Zn(OH)42-. Zinc particles were coated with SiO2 (thickness: 15 nm) by chemical solution deposition and with Zn2SiO4 (thickness: 20 nm) by chemical vapor deposition. These coatings formed a Si(OH)4 gel in aqueous KOH and retarded hydrogen evolution by 40%. By treatment in aqueous KOH and drying afterwards, the silica coatings were changed into ZnO-K2O·SiO2 layers. In this work, the electrochemical performance of such coated zinc particles is investigated by different electrochemical methods in order to gain a deeper understanding of the mechanisms of the coatings, which reduce zinc passivation. In particular, zinc utilization and changes in internal resistance are investigated. Moreover, methods for determination of diffusion coefficients, charge carrier numbers and activation energies for electrochemical oxidation are determined. SiO2-coated zinc particles show improved discharge capacity (CVD-coated zinc: 69% zinc utilization, CSD-coated zinc: 62% zinc utilization) as compared to as-received zinc (57% zinc utilization) at C/20 rate, by reducing supersaturation of zincates. Additionally, KOH-modified SiO2-coated zinc particles enhance rechargeability after 100% depth-of-discharge.

  15. Zinc Levels in Left Ventricular Hypertrophy.

    PubMed

    Huang, Lei; Teng, Tianming; Bian, Bo; Yao, Wei; Yu, Xuefang; Wang, Zhuoqun; Xu, Zhelong; Sun, Yuemin

    2017-03-01

    Zinc is one of the most important trace elements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and left ventricular hypertrophy (LVH). A total of 519 patients was enrolled and their serum zinc levels were measured in this study. We performed analyses on the relationship between zinc levels and LVH and the four LV geometry pattern patients: normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH. We performed further linear and multiple regression analyses to confirm the relationship between zinc and left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). Our data showed that zinc levels were 710.2 ± 243.0 μg/L in the control group and were 641.9 ± 215.2 μg/L in LVH patients. We observed that zinc levels were 715 ± 243.5 μg/L, 694.2 ± 242.7 μg/L, 643.7 ± 225.0 μg/L, and 638.7 ± 197.0 μg/L in normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH patients, respectively. We further found that there was a significant inverse linear relationship between zinc and LVM (p = 0.001) and LVMI (p = 0.000) but did not show a significant relationship with RWT (p = 0.561). Multiple regression analyses confirmed that the linear relationship between zinc and LVM and LVMI remained inversely significant. The present study revealed that serum zinc levels were significantly decreased in the LVH patients, especially in the eccentric LVH and concentric LVH patients. Furthermore, zinc levels were significantly inversely correlated with LVM and LVMI.

  16. Preparation, characterization and bioactivities of Athelia rolfsii exopolysaccharide-zinc complex (AEPS-zinc).

    PubMed

    Dong, Jinman; Li, Hongmei; Min, Weihong

    2018-07-01

    A new Athelia rolfsii exopolysaccharides (AEPS) were purified by Sephacryl S-300 and S-200. The physicochemical characteristics of AEPS fractions were assayed by HPGPC and GC methods. The structures of AEPS and AEPS‑zinc complex were characterized by SEM, FTIR and NMR. Moreover, the bioactivities of complex were also evaluated by experiments in vitro and in vivo. AEPSI consisted of glucose, galacturonic acid, talose, galactose, mannose and xylose, the relative contents of them were 24.74, 19.60, 33.65, 8.77, 7.97 and 5.28%, respectively. AEPSII consisted of glucose, inositol, galacturonic acid, ribitol, gluconic acid, talose and xylose, whose relative contents were 36.06, 21.21, 12.78, 11.07, 6.58, 5.45 and 6.82%, respectively. The Mw and Mn of AEPSI were 6.1324×10 4 and 1.4218×10 4 Da, those of AEPSII were 517 and 248Da. SEM observations showed that microstructures of AEPS and AEPS‑zinc complex were obviously different both in size and shape. FTIR and NMR analysis indicated that AEPS might chelate with zinc ion through hydroxy and carboxy group. In vitro experiments showed that AEPS‑zinc complex had a good bioavailability, in vivo experiments showed that it had good effect on improving zinc deficiency and antioxidant activities, which suggested that it could be used as zinc supplementation with high antioxidant activities. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. History of zinc in agriculture

    USDA-ARS?s Scientific Manuscript database

    Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, over 20 years would past before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure a parakeratosis in swine. In 1958, it wa...

  18. Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: acrodermatitis enteropathica and transient neonatal zinc deficiency as examples.

    PubMed

    Kasana, Shakhenabat; Din, Jamila; Maret, Wolfgang

    2015-01-01

    Discovering genetic causes of zinc deficiency has been a remarkable scientific journey. It started with the description of a rare skin disease, its treatment with various agents, the successful therapy with zinc, and the identification of mutations in a zinc transporter causing the disease. The journey continues with defining the molecular and cellular pathways that lead to the symptoms caused by zinc deficiency. Remarkably, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency. One is ZIP4, which is involved in intestinal zinc uptake. Its mutations can cause acrodermatitis enteropathica (AE) with autosomal recessive inheritance. The other one is ZnT2, the transporter responsible for supplying human milk with zinc. Mutations in this transporter cause transient neonatal zinc deficiency (TNZD) with symptoms similar to AE but with autosomal dominant inheritance. The two diseases can be distinguished in affected infants. AE is fatal if zinc is not supplied to the infant after weaning, whereas TNZD is a genetic defect of the mother limiting the supply of zinc in the milk, and therefore the infant usually will obtain enough zinc once weaned. Although these diseases are relatively rare, the full functional consequences of the numerous mutations in ZIP4 and ZnT2 and their interactions with dietary zinc are not known. In particular, it remains unexplored whether some mutations cause milder disease phenotypes or increase the risk for other diseases if dietary zinc requirements are not met or exceeded. Thus, it is not known whether widespread zinc deficiency in human populations is based primarily on a nutritional deficiency or determined by genetic factors as well. This consideration becomes even more significant with regard to mutations in the other 22 human zinc transporters, where associations with a range of diseases, including diabetes, heart disease, and mental illnesses have been observed

  19. Dynamic docking and electron transfer between Zn-myoglobin and cytochrome b(5).

    PubMed

    Liang, Zhao-Xun; Nocek, Judith M; Huang, Kai; Hayes, Ryan T; Kurnikov, Igor V; Beratan, David N; Hoffman, Brian M

    2002-06-19

    We present a broad study of the effect of neutralizing the two negative charges of the Mb propionates on the interaction and electron transfer (ET) between horse Mb and bovine cyt b(5), through use of Zn-substituted Mb (ZnMb, 1) to study the photoinitiated reaction, ((3)ZnP)Mb + Fe(3+)cyt b(5) --> (ZnP)(+)Mb + Fe(2+)cyt b(5). The charge neutralization has been carried out both by replacing the Mb heme with zinc-deuteroporphyrin dimethylester (ZnMb(dme), 2), which replaces the charges by small neutral hydrophobic patches, and also by replacement with the newly prepared zinc-deuteroporphyrin diamide (ZnMb(diamide), 3), which converts the charged groups to neutral, hydrophilic ones. The effect of propionate neutralization on the conformation of the zinc-porphyrin in the Mb heme pocket has been studied by multinuclear NMR with an (15)N labeled zinc porphyrin derivative (ZnMb((15)N-diamide), 4). The rates of photoinitiated ET between the Mb's (1-3) and cyt b(5) have been measured over a range of pH values and ionic strengths. Isothermal titration calorimetry (ITC) and NMR methods have been used to independently investigate the effect of charge neutralization on Mb/b(5) binding. The neutralization of the two heme propionates of ZnMb by formation of the heme diester or, for the first time, the diamide increases the second-order rate constant of the ET reaction between ZnMb and cyt b(5) by as much as several 100-fold, depending on pH and ionic strength, while causing negligible changes in binding affinity. Brownian dynamic (BD) simulations and ET pathway calculations provide insight into the protein docking and ET process. The results support a new "dynamic docking" paradigm for protein-protein reactions in which numerous weakly bound conformations of the docked complex contribute to the binding of cyt b(5) to Mb and Hb, but only a very small subset of these are ET active, and this subset does not include the conformations most favorable for binding; the Mb surface is a

  20. The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

    PubMed Central

    Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

    2009-01-01

    The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

  1. Improved colorimetric determination of serum zinc.

    PubMed

    Johnson, D J; Djuh, Y Y; Bruton, J; Williams, H L

    1977-07-01

    We show how zinc may easily be quantified in serum by first using an optimum concentration of guanidine hydrochloride to cause release of zinc from proteins, followed by complexation of released metals with cyanide. The cyanide complex of zinc is preferentially demasked with chloral hydrate, followed by a colorimetric reaction between zinc and 4-(2-pyridylazo)resorcinol. This is a sensitive water-soluble ligand; its complex with zinc has an absorption maximum at 497 nm. Values found by this technique compare favorably with those obtained by atomic absorption spectroscopy.

  2. [Geriatric rehabilitation from the perspective of Book 9 of the German social code, SGB IX].

    PubMed

    Fuchs, H

    2007-10-01

    The legal foundations for provision and realization of geriatric rehabilitation benefits are contained in particular in Book 9 of the German social code, SGB IX (covering rehabilitation and participation of people with disabilities). This paper discusses claims foundations and benefit prerequisites of geriatric rehabilitation taking into consideration the relations between Book 5 (on health insurance) and Book 9 of the social code. The article includes a definition of "geriatric rehabilitation" in light of the SGB IX, describes the benefit carriers' obligations as well as the procedure in place for determining geriatric rehab need, in this context appraising the designation as "geriatric patient" in terms of its appropriateness as an identifying criterion in determining need. Provision of geriatric rehab benefits is contingent on a potential for attaining rehab goals as specified by SGB IX as well as on fulfillment of the benefit prerequisites. Responsibility for the content, extent and quality of geriatric rehabilitation lies with the benefit carriers, as is the case for the obligation to secure availability of the required numbers and quality of rehabilitation facilities and services. The article specifies the legal foundations of the various benefit types (ambulatory, mobile rehab, under a Personal Budget, integrated benefit provision, or early rehab), and discusses geriatric rehabilitation in the framework of an insurance-based medical care system as well as of activating care.

  3. Photovoltaic cells employing zinc phosphide

    DOEpatents

    Barnett, Allen M.; Catalano, Anthony W.; Dalal, Vikram L.; Masi, James V.; Meakin, John D.; Hall, Robert B.

    1984-01-01

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  4. Modeling the temporal variability of zinc concentrations in zinc roof runoff-experimental study and uncertainty analysis.

    PubMed

    Sage, Jérémie; El Oreibi, Elissar; Saad, Mohamed; Gromaire, Marie-Christine

    2016-08-01

    This study investigates the temporal variability of zinc concentrations from zinc roof runoff. The influence of rainfall characteristics and dry period duration is evaluated by combining laboratory experiment on small zinc sheets and in situ measurements under real weather conditions from a 1.6-m(2) zinc panel. A reformulation of a commonly used conceptual runoff quality model is introduced and its ability to simulate the evolution of zinc concentrations is evaluated. A systematic and sharp decrease from initially high to relatively low and stable zinc concentrations after 0.5 to 2 mm of rainfall is observed for both experiments, suggesting that highly soluble corrosion products are removed at early stages of runoff. A moderate dependence between antecedent dry period duration and the magnitude of zinc concentrations at the beginning of a rain event is evidenced. Contrariwise, results indicate that concentrations are not significantly influenced by rainfall intensities. Simulated rainfall experiment nonetheless suggests that a slight effect of rainfall intensities may be expected after the initial decrease of concentrations. Finally, this study shows that relatively simple conceptual runoff quality models may be adopted to simulate the variability of zinc concentrations during a rain event and from a rain event to another.

  5. Short-Term Subclinical Zinc Deficiency in Weaned Piglets Affects Cardiac Redox Metabolism and Zinc Concentration.

    PubMed

    Brugger, Daniel; Windisch, Wilhelm M

    2017-04-01

    Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism. Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets. Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients. Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively ( P < 0.0001). Further reduction in dietary zinc promoted a linear decrease of glutathione and α-tocopherol (30 and 0.6 nmol/mg dietary Zn, respectively; P < 0.05) and a linear increase of gene expression [0.02, 0.01, 0.003, and 0.02 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05)]. Tissue zinc declined linearly with reduction in dietary zinc (0.21 mg tissue Zn/mg dietary Zn; P = 0.004) from 88.0 to 42.7 mg/kg ( P < 0.0001), below which it linearly increased inversely to further reduction in dietary zinc (0.57 mg tissue Zn/mg dietary Zn; P = 0.006). H 2 O 2 -detoxification activity and metallothionein 1A gene expression decreased linearly with reduction in dietary zinc from 88.0 to 28.1 mg/kg [0.02 mU and 0.008 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05]. Fas cell-surface death receptor, etoposide-induced 2.4 and cyclin-dependent kinase inhibitor 1A gene expression correlated

  6. Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer

    PubMed Central

    Buchlis, George; Podsakoff, Gregory M.; Radu, Antonetta; Hawk, Sarah M.; Flake, Alan W.; Mingozzi, Federico

    2012-01-01

    In previous work we transferred a human factor IX–encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer. PMID:22271447

  7. Monte Carlo modeling of in vivo protoporphyrin IX fluorescence and singlet oxygen production during photodynamic therapy for patients presenting with superficial basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Valentine, Ronan M.; Brown, C. Tom A.; Moseley, Harry; Ibbotson, Sally; Wood, Kenny

    2011-04-01

    We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 +/- 1 J/cm2. Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm2 could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.

  8. Effectiveness of CAI Package on Achievement in Physics of IX Standard Students

    ERIC Educational Resources Information Center

    Maheswari, I. Uma; Ramakrishnan, N.

    2015-01-01

    The present study is an experimental one in nature, to find out the effectiveness of CAI package on in Physics of IX std. students. For this purpose a CAI package was developed and validated. The validated CAI package formed an independent variable of this study. The dependent variable is students' achievements in physics content. In order to find…

  9. Zinc titanate sorbents

    DOEpatents

    Gupta, R.P.; Gangwal, S.K.; Jain, S.C.

    1998-02-03

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750 to about 950 C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 microns, and about 1 part titanium dioxide having a median particle size of less than about 1 micron. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  10. Zinc titanate sorbents

    DOEpatents

    Gupta, Raghubir P.; Gangwal, Santosh K.; Jain, Suresh C.

    1998-01-01

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750.degree. C. to about 950.degree. C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 .mu., and about 1 part titanium dioxide having a median particle size of less than about 1 .mu.. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  11. Zinc in innate and adaptive tumor immunity

    PubMed Central

    2010-01-01

    Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order. PMID:21087493

  12. Effects of Different Zinc Species on Cellar Zinc Distribution, Cell Cycle, Apoptosis and Viability in MDAMB231 Cells.

    PubMed

    Wang, Yan-hong; Zhao, Wen-jie; Zheng, Wei-juan; Mao, Li; Lian, Hong-zhen; Hu, Xin; Hua, Zi-chun

    2016-03-01

    Intracellular metal elements exist in mammalian cells with the concentration range from picomoles per litre to micromoles per litre and play a considerable role in various biological procedures. Element provided by different species can influence the availability and distribution of the element in a cell and could lead to different biological effects on the cell's growth and function. Zinc as an abundant and widely distributed essential trace element, is involved in numerous and relevant physiological functions. Zinc homeostasis in cells, which is regulated by metallothioneins, zinc transporter/SLC30A, Zrt-/Irt-like proteins/SLC39A and metal-response element-binding transcription factor-1 (MTF-1), is crucial for normal cellular functioning. In this study, we investigated the influences of different zinc species, zinc sulphate, zinc gluconate and bacitracin zinc, which represented inorganic, organic and biological zinc species, respectively, on cell cycle, viability and apoptosis in MDAMB231 cells. It was found that the responses of cell cycle, apoptosis and death to different zinc species in MDAMB231 cells are different. Western blot analysis of the expression of several key proteins in regulating zinc-related transcription, cell cycle, apoptosis, including MTF-1, cyclin B1, cyclin D1, caspase-8 and caspase-9 in treated cells further confirmed the observed results on cell level.

  13. Overexpression of Plastidic Protoporphyrinogen IX Oxidase Leads to Resistance to the Diphenyl-Ether Herbicide Acifluorfen1

    PubMed Central

    Lermontova, Inna; Grimm, Bernhard

    2000-01-01

    The use of herbicides to control undesirable vegetation has become a universal practice. For the broad application of herbicides the risk of damage to crop plants has to be limited. We introduced a gene into the genome of tobacco (Nicotiana tabacum) plants encoding the plastid-located protoporphyrinogen oxidase of Arabidopsis, the last enzyme of the common tetrapyrrole biosynthetic pathway, under the control of the cauliflower mosaic virus 35S promoter. The transformants were screened for low protoporphyrin IX accumulation upon treatment with the diphenyl ether-type herbicide acifluorfen. Leaf disc incubation and foliar spraying with acifluorfen indicated the lower susceptibility of the transformants against the herbicide. The resistance to acifluorfen is conferred by overexpression of the plastidic isoform of protoporphyrinogen oxidase. The in vitro activity of this enzyme extracted from plastids of selected transgenic lines was at least five times higher than the control activity. Herbicide treatment that is normally inhibitory to protoporphyrinogen IX oxidase did not significantly impair the catalytic reaction in transgenic plants and, therefore, did not cause photodynamic damage in leaves. Therefore, overproduction of protoporphyrinogen oxidase neutralizes the herbicidal action, prevents the accumulation of the substrate protoporphyrinogen IX, and consequently abolishes the light-dependent phytotoxicity of acifluorfen. PMID:10631251

  14. Status of zinc injection in PWRs

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

    Bergmann, C.A.

    1995-03-01

    Based on laboratory and other studies, it was concluded that zinc addition in a PWR primary coolant should result in reduced Alloy 600 PWSCC and general corrosion rates of the materials of construction. Because of these positive results, a Westinghouse Owner`s Subgroup, EPRI, and Westinghouse provided funds to continue the development and application of zinc in an operating plant. As part of the program, Southern Operating Nuclear Company agreed to operate the Farley 2 plant with zinc addition as a demonstration test of the effectiveness of zinc. Since zinc is incorporated in the corrosion oxide film on the primary systemmore » surfaces and Farley 2 is a mature plant, it was estimated that about 10 kgs of zinc would be needed to condition the plant before an equilibrium value in the coolant would be reached. The engineered aspects of a Zinc Addition and Monitoring System (ZAMS) considered such items as the constitutents, location, sizing and water supply of the ZAMS. Baseline data such as the PWSCC history of the Alloy 600 steam generator tubing, fuel oxide thickness, fuel crud deposits, radiation levels, and RCP seal leak-off rates were obtained before zinc addition is initiated. This presentation summarizes some of the work performed under the program, and the status of zinc injection in the Farley 2 plant.« less

  15. Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role of zinc-metallothionein in zinc-induced genoprotection.

    PubMed

    Jourdan, Eric; Emonet-Piccardi, Nathalie; Didier, Christine; Beani, Jean-Claude; Favier, Alain; Richard, Marie-Jeanne

    2002-09-15

    Zinc is an essential oligoelement for cell growth and cell survival and has been demonstrated to protect cells from oxidative stress induced by UVA or from genotoxic stress due to UVB. In a recent work we demonstrated that the antioxidant role of zinc could be related to its ability to induce metallothioneins (MTs). In this study we identified the mechanism of zinc protection against solar-simulated light (SSL) injury. Cultured human keratinocytes (HaCaT) were used to examine MTs expression and localization in response to solar-simulated radiation. We found translocation to the nucleus, with overexpression of MTs in irradiated cells, a novel observation. The genoprotective effect of zinc was dependent on time and protein synthesis. DNA damage was significantly decreased after 48 h of ZnCl(2) (100 microM) treatment and is inhibited by actinomycin D. ZnCl(2) treatment (100 microM) led to an intense induction, redistribution, and accumulation of MT in the nucleus of irradiated cells. MT expression correlated with the time period of ZnCl(2) treatment. CdCl(2), a potent MT inducer, did not show any genoprotection, although the MTs were expressed in the nucleus. Overall our findings demonstrate that MTs could be a good candidate for explaining the genoprotection mediated by zinc on irradiated cells.

  16. Systematic review of zinc fortification trials.

    PubMed

    Das, Jai K; Kumar, Rohail; Salam, Rehana A; Bhutta, Zulfiqar A

    2013-01-01

    Zinc is one of the essential trace elements required by the human body as it is present in more than a hundred specific enzymes and serves as an important structural ion in transcription factors. Around one third of the world population lives in countries with a high prevalence of zinc deficiency. Food fortification with zinc seems to be an attractive public health strategy and a number of programs have been initiated, especially in developing countries. We conducted a systematic review to assess the efficacy of zinc fortification. A total of 11 studies with 771 participants were included in our analysis. Zinc fortification was associated with significant improvements in plasma zinc concentrations [standard mean difference (SMD) 1.28, 95% CI 0.56, 2.01] which is a functional indicator of zinc status. Significant improvement was observed for height velocity (SMD 0.52, 95% CI 0.01, 1.04); however, this finding was weak and based on a restricted analysis. Further subgroup analysis showed significant improvement in height velocity among very-low-birth-weight infants (SMD 0.70, 95% CI 0.02, 1.37), while for healthy newborns, the impact was insignificant. Zinc fortification had insignificant impacts on serum alkaline levels, serum copper levels, hemoglobin and weight gain. Although the findings highlight that zinc fortification is associated with an increased serum concentration of the micronutrient, overall evidence of the effectiveness of this approach is limited. Data on pregnant and lactating women is scarce. Large-scale fortification programs with robust impact assessment should be initiated to cover larger populations in all age groups. Mass fortification of zinc may be a cost-effective strategy to overcome zinc deficiency. Copyright © 2013 S. Karger AG, Basel.

  17. Venous drainage of the dorsal sector of the liver: differences between segments I and IX. A study on corrosion casts of the human liver.

    PubMed

    Gadzijev, E M; Ravnik, D; Stanisavljevic, D; Trotovsek, B

    1997-01-01

    The aim of this study was to determine the venous drainage of the dorsal sector of the liver in order to define the differences between segments I and IX and their implications for sectorially and segmentally oriented hepatic surgery. The study was based on corrosion casts of 61 macroscopically healthy livers. The drainage pathways of veins at least 10 mm long and 1 mm wide were evaluated and statistically analysed. On average, 9 veins drained the two segments and three veins from both segments entered the inferior vena cava. In 95% of cases the veins from segment I drained predominantly into the inferior vena cava, whereas in segment IX this pathway was dominant in only 30% of cases. In 64% of cases a vein originating in segment IX entered the right hepatic v. The difference in the venous drainage of the two segments suggests that segment IX partly belongs to the neighbouring segments and may thus be only a paracaval region of the right liver.

  18. Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome.

    PubMed

    Rivera, C E; Villagra, J; Riordan, M; Williams, S; Lindstrom, K J; Rick, M E

    2001-01-01

    We describe a new mutation in glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome (BSS). Sequencing of GPIX revealed a homozygous (T-->C) transition at nucleotide 1717 (GenBank/HUMGPIX/M80478), resulting in a Cys(8) (TGT)-->Arg (CGT) replacement in the mature peptide. DNA restriction enzyme analysis using BsaAI revealed that the patient was homozygous and that his parents were heterozygous for the defect. This mutation disrupts a putative disulphide bond between the Cys(8) and Cys(12) that would alter the secondary structure of GPIX and which probably accounts for the absence of the GPIb/IX/V complex from the platelet surface in this patient.

  19. The Relationship between Zinc Intake and Serum/Plasma Zinc Concentration in Children: A Systematic Review and Dose-Response Meta-Analysis

    PubMed Central

    Moran, Victoria Hall; Stammers, Anna-Louise; Medina, Marisol Warthon; Patel, Sujata; Dykes, Fiona; Souverein, Olga W.; Dullemeijer, Carla; Pérez-Rodrigo, Carmen; Serra-Majem, Lluis; Nissensohn, Mariela; Lowe, Nicola M.

    2012-01-01

    Recommendations for zinc intake during childhood vary widely across Europe. The EURRECA project attempts to consolidate the basis for the definition of micronutrient requirements, taking into account relationships among intake, status and health outcomes, in order to harmonise these recommendations. Data on zinc intake and biomarkers of zinc status reported in randomised controlled trials (RCTs) can provide estimates of dose-response relationships which may be used for underpinning zinc reference values. This systematic review included all RCTs of apparently healthy children aged 1–17 years published by February 2010 which provided data on zinc intake and biomarkers of zinc status. An intake-status regression coefficient () was calculated for each individual study and calculated the overall pooled and SE () using random effects meta-analysis on a double log scale. The pooled dose-response relationship between zinc intake and zinc status indicated that a doubling of the zinc intake increased the serum/plasma zinc status by 9%. This evidence can be utilised, together with currently used balance studies and repletion/depletion studies, when setting zinc recommendations as a basis for nutrition policies. PMID:23016120

  20. Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation1

    PubMed Central

    Wessells, K. Ryan; Hess, Sonja Y.; Rouamba, Noel; Ouédraogo, Zinewendé P.; Kellogg, Mark; Goto, Rie; Duggan, Christopher; Ouédraogo, Jean-Bosco; Brown, Kenneth H.

    2015-01-01

    Objectives Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12 and folate; however, little information is available on mineral absorption. We therefore investigated the relationship between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc absorption, as estimated by the change in plasma zinc concentration (PZC) following short-term zinc or placebo supplementation. Methods We conducted a randomized, partially-masked, placebo-controlled trial among 282 apparently healthy children 6–23 mo of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg zinc, as zinc sulfate, or placebo, daily for 21 d. Results At baseline, mean ± SD PZC was 62.9 ± 11.9 µg/dL; median (IQR) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentration were 0.04 (0.03 – 0.07) and 11.4 (9.0 – 15.6) µmol/L, respectively. Change in PZC was significantly greater in the zinc supplemented versus placebo group (15.6 ± 13.3 µg/dL vs. 0.02 ± 10.9 µg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (−1.1 µg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relationship did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC. Conclusions Although altered intestinal permeability may reduce dietary zinc absorption, it likely does not undermine the efficacy of zinc supplementation, given the large increases in PZC following short-term zinc supplementation observed in this study, even among those with increased urinary L:M recovery ratios. PMID:23689263

  1. VizieR Online Data Catalog: Atomic data for X-ray lines of FeVIII and FeIX (O'Dwyer+, 2012)

    NASA Astrophysics Data System (ADS)

    O'Dwyer, B.; Del Zanna, G.; Badnell, N. R.; Mason, H. E.; Storey, P. J.

    2012-04-01

    The distorted wave extension of the autostructure code has been used to calculate energy levels, radiative transition probabilities and collisional excitation rates of Fe VIII and Fe IX up to n=6 for Fe IX and n=7 for Fe VIII. We have compared some of the data with previous calculations, finding overall agreement for radiative transition rates, but interesting differences for some collisional data. ************************************************************************** * * * Sorry, but the author(s) never supplied the tabular material * * announced in the paper * * * **************************************************************************

  2. A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations123

    PubMed Central

    Zyba, Sarah J; Killilea, David W; Holland, Tai C; Kim, Elijah; Moy, Adrian; Sutherland, Barbara; Shigenaga, Mark K

    2017-01-01

    Background: Food fortification has been recommended to improve a population’s micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. Objective: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status. Design: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period. Results: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase. Conclusions: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352. PMID:28003206

  3. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, Toshifumi

    1997-01-01

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate .alpha.-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal.

  4. Ferritin: a zinc detoxicant and a zinc ion donor.

    PubMed Central

    Price, D; Joshi, J G

    1982-01-01

    Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

  5. Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

    PubMed

    Fidanzi-Dugas, Chloë; Liagre, Bertrand; Chemin, Guillaume; Perraud, Aurélie; Carrion, Claire; Couquet, Claude-Yves; Granet, Robert; Sol, Vincent; Léger, David Yannick

    2017-07-01

    Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE 2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Decision Making in Intercollegiate Athletics: One Institution's Journey to Maintain Title IX Compliance

    ERIC Educational Resources Information Center

    Rowland, John W.

    2012-01-01

    The allocation of resources and participation opportunities in intercollegiate athletics has been a debate among researchers for nearly 40 years. Title IX and traditionally male-dominated budgeting practices continue to be opposing forces that shape the financial and gender makeup of university athletic departments. In fact, the need to be Title…

  7. Title IX: Does Help for Women Come at the Expense of African Americans?

    ERIC Educational Resources Information Center

    Greenlee, Craig T.

    1997-01-01

    Federal law that forbids sex discrimination in educational institutions receiving federal funds (Title IX) has created opportunities for women athletes, but some say men's sports have lost ground. Since athletics provide major educational opportunities for black men, less so for black women, critics are concerned blacks may be losing. (MSE)

  8. Ares I-X First Stage Internal Aft Skirt Re-Entry Heating Data and Modeling

    NASA Technical Reports Server (NTRS)

    Schmitz, Craig P.; Tashakkor, Scott B.

    2011-01-01

    The CLVSTATE engineering code is being used to predict Ares-I launch vehicle first stage reentry aerodynamic heating. An engineering analysis is developed which yields reasonable predictions for the timing of the first stage aft skirt thermal curtain failure and the resulting internal gas temperatures. The analysis is based on correlations of the Ares I-X internal aft skirt gas temperatures and has been implemented into CLVSTATE. Validation of the thermal curtain opening models has been accomplished using additional Ares I-X thermocouple, calorimeter and pressure flight data. In addition, a technique which accounts for radiation losses at high altitudes has been developed which improves the gas temperature measurements obtained by the gas temperature probes (GTP). Updates to the CLVSTATE models are shown to improve the accuracy of the internal aft skirt heating predictions which will result in increased confidence in future vehicle designs

  9. Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors.

    PubMed

    Akocak, Suleyman; Lolak, Nabih; Nocentini, Alessio; Karakoc, Gulcin; Tufan, Anzel; Supuran, Claudiu T

    2017-06-15

    A series of sixteen novel aromatic and heterocyclic bis-sulfonamide Schiff bases were prepared by conjugation of well known aromatic and heterocyclic aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores with aromatic and heterocyclic bis-aldehydes. The obtained bis-sulfonamide Schiff bases were investigated as inhibitors of four selected human (h) CA isoforms, hCA I, hCA II, hCA VII and hCA IX. Most of the newly synthesized compounds showed a good inhibitory profile against isoforms hCA II and hCA IX, also showing moderate selectivity against hCA I and VII. Several efficient lead compounds were identified among this bis-sulfonamide Schiff bases with low nanomolar to sub-nanomolar activity against hCA II (K i s ranging between 0.4 and 861.1nM) and IX (K i s between 0.5 and 933.6nM). Since hCA II and hCA IX are important drug targets (antiglaucoma and anti-tumor agents), these isoform-selective inhibitors may be considered of interest for various biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. INTER- AND INTRA-CLUSTER AGE GRADIENTS IN MASSIVE STAR FORMING REGIONS AND INDIVIDUAL NEARBY STELLAR CLUSTERS REVEALED BY MYStIX

    NASA Astrophysics Data System (ADS)

    Getman, Konstantin V.; Feigelson, Eric; Kuhn, Michael A.; Broos, Patrick S; Townsley, Leisa K.; Naylor, Tim; Povich, Matthew S.; Luhman, Kevin; Garmire, Gordon

    2014-08-01

    The MYStIX (Massive Young Star-Forming Complex Study in Infrared and X-ray) project seeks to characterize 20 OB-dominated young star forming regions (SFRs) at distances <4 kpc using photometric catalogs from the Chandra X-ray Observatory, Spitzer Space Telescope, UKIRT and 2MASS surveys. As part of the MYStIX project, we developed a new stellar chronometer that employs near-infrared and X-ray photometry data, AgeJX. Computing AgeJX averaged over MYStIX (sub)clusters reveals previously unknown age gradients across most of the MYStIX regions as well as within some individual rich clusters. Within the SFRs, the inferred AgeJX ages are youngest in obscured locations in molecular clouds, intermediate in revealed stellar clusters, and oldest in distributed stellar populations. Noticeable intra-cluster gradients are seen in the NGC 2024 (Flame Nebula) star cluster and the Orion Nebula Cluster (ONC): stars in cluster cores appear younger and thus were formed later than stars in cluster halos. The latter result has two important implications for the formation of young stellar clusters. Clusters likely form slowly: they do not arise from a single nearly-instantaneous burst of star formation. The simple models where clusters form inside-out are likely incorrect, and more complex models are needed. We provide several star formation scenarios that alone or in combination may lead to the observed core-halo age gradients.

  11. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, T.

    1997-02-18

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate {alpha}-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal. 33 figs.

  12. Recovery of zinc and manganese from alkaline and zinc-carbon spent batteries

    NASA Astrophysics Data System (ADS)

    De Michelis, I.; Ferella, F.; Karakaya, E.; Beolchini, F.; Vegliò, F.

    This paper concerns the recovery of zinc and manganese from alkaline and zinc-carbon spent batteries. The metals were dissolved by a reductive-acid leaching with sulphuric acid in the presence of oxalic acid as reductant. Leaching tests were realised according to a full factorial design, then simple regression equations for Mn, Zn and Fe extraction were determined from the experimental data as a function of pulp density, sulphuric acid concentration, temperature and oxalic acid concentration. The main effects and interactions were investigated by the analysis of variance (ANOVA). This analysis evidenced the best operating conditions of the reductive acid leaching: 70% of manganese and 100% of zinc were extracted after 5 h, at 80 °C with 20% of pulp density, 1.8 M sulphuric acid concentration and 59.4 g L -1 of oxalic acid. Both manganese and zinc extraction yields higher than 96% were obtained by using two sequential leaching steps.

  13. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    Varistors and/or resistors that includes doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  14. Low-Resistivity Zinc Selenide for Heterojunctions

    NASA Technical Reports Server (NTRS)

    Stirn, R. J.

    1986-01-01

    Magnetron reactive sputtering enables doping of this semiconductor. Proposed method of reactive sputtering combined with doping shows potential for yielding low-resistivity zinc selenide films. Zinc selenide attractive material for forming heterojunctions with other semiconductor compounds as zinc phosphide, cadmium telluride, and gallium arsenide. Semiconductor junctions promising for future optoelectronic devices, including solar cells and electroluminescent displays. Resistivities of zinc selenide layers deposited by evaporation or chemical vapor deposition too high to form practical heterojunctions.

  15. Ares I-X Range Safety Simulation and Analysis IV and V

    NASA Technical Reports Server (NTRS)

    Merry, Carl M.; Brewer, Joan D.; Dulski, Matt B.; Gimenez, Adrian; Barron, Kyle; Tarpley, Ashley F.; Craig, A. Scott; Beaty, Jim R.; Starr, Brett R.

    2011-01-01

    NASA s Ares I-X vehicle launched on a suborbital test flight from the Eastern Range in Florida on October 28, 2009. NASA generated a Range Safety (RS) product data package to meet the RS trajectory data requirements defined in the Air Force Space Command Manual (AFSPCMAN) 91-710. Some products included were a nominal ascent trajectory, ascent flight envelopes, and malfunction turn data. These products are used by the Air Force s 45th Space Wing (45SW) to ensure public safety and to make flight termination decisions on launch day. Due to the criticality of the RS data, an independent validation and verification (IV&V) effort was undertaken to accompany the data generation analyses to ensure utmost data quality and correct adherence to requirements. As a result of the IV&V efforts, the RS product package was delivered with confidence that two independent organizations using separate simulation software generated data to meet the range requirements and yielded similar results. This document captures the Ares I-X RS product IV&V analysis, including the methodology used to verify inputs, simulation, and output data for certain RS products. Additionally a discussion of lessons learned is presented to capture advantages and disadvantages to the IV&V processes used.

  16. Enforcing Title IX. A Report of the U.S. Commission on Civil Rights.

    ERIC Educational Resources Information Center

    Commission on Civil Rights, Washington, DC.

    This report reassesses for the Department of Education (ED) the enforcement effort of Title IX by the Office for Civil Rights (OCR) and offers recommendations. OCR is criticized for being very slow to issue important guidelines, process complaints, conduct compliance reviews, and enforce the law. Also OCR is charged with showing little commitment…

  17. African Swine Fever Virus p72 Genotype IX in Domestic Pigs, Congo, 2009

    PubMed Central

    Anchuelo, Raquel; Pelayo, Virginia; Poudevigne, Frédéric; Leon, Tati; Nzoussi, Jacques; Bishop, Richard; Pérez, Covadonga; Soler, Alejandro; Nieto, Raquel; Martín, Hilario; Arias, Marisa

    2011-01-01

    African swine fever virus p72 genotype IX, associated with outbreaks in eastern Africa, is cocirculating in the Republic of the Congo with West African genotype I. Data suggest that viruses from eastern Africa are moving into western Africa, increasing the threat of outbreaks caused by novel viruses in this region. PMID:21801650

  18. Effects of serum zinc level on tinnitus.

    PubMed

    Berkiten, Güler; Kumral, Tolgar Lütfi; Yıldırım, Güven; Salturk, Ziya; Uyar, Yavuz; Atar, Yavuz

    2015-01-01

    The aim of this study was to assess zinc levels in tinnitus patients, and to evaluate the effects of zinc deficiency on tinnitus and hearing loss. One-hundred patients, who presented to an outpatient clinic with tinnitus between June 2009 and 2014, were included in the study. Patients were divided into three groups according to age: Group I (patients between 18 and 30years of age); Group II (patients between 31 and 60years of age); and Group III (patients between 61 and 78years of age). Following a complete ear, nose and throat examination, serum zinc levels were measured and the severity of tinnitus was quantified using the Tinnitus Severity Index Questionnaire (TSIQ). Patients were subsequently asked to provide a subjective judgment regarding the loudness of their tinnitus. The hearing status of patients was evaluated by audiometry and high-frequency audiometry. An average hearing sensitivity was calculated as the mean value of hearing thresholds between 250 and 20,000Hz. Serum zinc levels between 70 and 120μg/dl were considered normal. The severity and loudness of tinnitus, and the hearing thresholds of the normal zinc level and zinc-deficient groups, were compared. Twelve of 100 (12%) patients exhibited low zinc levels. The mean age of the zinc-deficient group was 65.41±12.77years. Serum zinc levels were significantly lower in group III (p<0.01). The severity and loudness of tinnitus were greater in zinc-deficient patients (p=0.011 and p=0.015, respectively). Moreover, the mean thresholds of air conduction were significantly higher in zinc-deficient patients (p=0.000). We observed that zinc levels decrease as age increases. In addition, there was a significant correlation between zinc level and the severity and loudness of tinnitus. Zinc deficiency was also associated with impairments in hearing thresholds. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Ares I-X Range Safety Flight Envelope Analysis

    NASA Technical Reports Server (NTRS)

    Starr, Brett R.; Olds, Aaron D.; Craig, Anthony S.

    2011-01-01

    Ares I-X was the first test flight of NASA's Constellation Program's Ares I Crew Launch Vehicle designed to provide manned access to low Earth orbit. As a one-time test flight, the Air Force's 45th Space Wing required a series of Range Safety analysis data products to be developed for the specified launch date and mission trajectory prior to granting flight approval on the Eastern Range. The range safety data package is required to ensure that the public, launch area, and launch complex personnel and resources are provided with an acceptable level of safety and that all aspects of prelaunch and launch operations adhere to applicable public laws. The analysis data products, defined in the Air Force Space Command Manual 91-710, Volume 2, consisted of a nominal trajectory, three sigma trajectory envelopes, stage impact footprints, acoustic intensity contours, trajectory turn angles resulting from potential vehicle malfunctions (including flight software failures), characterization of potential debris, and debris impact footprints. These data products were developed under the auspices of the Constellation's Program Launch Constellation Range Safety Panel and its Range Safety Trajectory Working Group with the intent of beginning the framework for the operational vehicle data products and providing programmatic review and oversight. A multi-center NASA team in conjunction with the 45th Space Wing, collaborated within the Trajectory Working Group forum to define the data product development processes, performed the analyses necessary to generate the data products, and performed independent verification and validation of the data products. This paper outlines the Range Safety data requirements and provides an overview of the processes established to develop both the data products and the individual analyses used to develop the data products, and it summarizes the results of the analyses required for the Ares I-X launch.

  20. Zinc Status of Vegetarians during Pregnancy: A Systematic Review of Observational Studies and Meta-Analysis of Zinc Intake.

    PubMed

    Foster, Meika; Herulah, Ursula Nirmala; Prasad, Ashlini; Petocz, Peter; Samman, Samir

    2015-06-05

    Pregnant women are vulnerable to a low zinc status due to the additional zinc demands associated with pregnancy and foetal development. The present systematic review explores the relationship between habitual vegetarian diets and dietary zinc intake/status during pregnancy. The association between vegetarian diets and functional pregnancy outcome also is considered. A literature search was conducted of MEDLINE; PubMed; Embase; the Cochrane Library; Web of Science; and Scopus electronic databases up to September 2014. Six English-language observational studies qualified for inclusion in the systematic review. A meta-analysis was conducted that compared the dietary zinc intake of pregnant vegetarian and non-vegetarian (NV) groups; the zinc intake of vegetarians was found to be lower than that of NV (-1.38 ± 0.35 mg/day; p < 0.001); and the exclusion of low meat eaters from the analysis revealed a greater difference (-1.53 ± 0.44 mg/day; p = 0.001). Neither vegetarian nor NV groups met the recommended dietary allowance (RDA) for zinc. In a qualitative synthesis; no differences were found between groups in serum/plasma zinc or in functional outcomes associated with pregnancy. In conclusion; pregnant vegetarian women have lower zinc intakes than NV control populations and both groups consume lower than recommended amounts. Further information is needed to determine whether physiologic adaptations in zinc metabolism are sufficient to meet maternal and foetal requirements during pregnancy on a low zinc diet.

  1. Zinc Status of Vegetarians during Pregnancy: A Systematic Review of Observational Studies and Meta-Analysis of Zinc Intake

    PubMed Central

    Foster, Meika; Herulah, Ursula Nirmala; Prasad, Ashlini; Petocz, Peter; Samman, Samir

    2015-01-01

    Pregnant women are vulnerable to a low zinc status due to the additional zinc demands associated with pregnancy and foetal development. The present systematic review explores the relationship between habitual vegetarian diets and dietary zinc intake/status during pregnancy. The association between vegetarian diets and functional pregnancy outcome also is considered. A literature search was conducted of MEDLINE; PubMed; Embase; the Cochrane Library; Web of Science; and Scopus electronic databases up to September 2014. Six English-language observational studies qualified for inclusion in the systematic review. A meta-analysis was conducted that compared the dietary zinc intake of pregnant vegetarian and non-vegetarian (NV) groups; the zinc intake of vegetarians was found to be lower than that of NV (−1.38 ± 0.35 mg/day; p < 0.001); and the exclusion of low meat eaters from the analysis revealed a greater difference (−1.53 ± 0.44 mg/day; p = 0.001). Neither vegetarian nor NV groups met the recommended dietary allowance (RDA) for zinc. In a qualitative synthesis; no differences were found between groups in serum/plasma zinc or in functional outcomes associated with pregnancy. In conclusion; pregnant vegetarian women have lower zinc intakes than NV control populations and both groups consume lower than recommended amounts. Further information is needed to determine whether physiologic adaptations in zinc metabolism are sufficient to meet maternal and foetal requirements during pregnancy on a low zinc diet. PMID:26056918

  2. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-07-27

    Varistors and/or resistors are described that include doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  3. Long life, rechargeable nickel-zinc battery

    NASA Technical Reports Server (NTRS)

    Luksha, E.

    1974-01-01

    A production version of the inorganic separator was evaluated for improving the life of the nickel-zinc system. Nickel-zinc cells (7-10 Ah capacities) of different electrode separator configurations were constructed and tested. The nickel-zinc cells using the inorganic separator encasing the zinc electrode, the nickel electrode, or both electrodes had shorter lives than cells using Visking and cellophane separation. Cells with the inorganic separation all fell below 70% of their theoretical capacity within 30 cycles, but the cells constructed with organic separation required 80 cycles. Failure of the cells using the ceramic separator was irreversible capacity degradation due to zinc loss through cracks developed in the inorganic separator. Zinc loss through the separator was minimized with the use of combinations of the inorganic separator with Visking and cellophane. Cells using the combined separation operated 130 duty cycles before degrading to 70% of their theoretical capacity.

  4. Stabilized nickel-zinc battery

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

    Himy, A.; Wagner, O.C.

    An alkaline nickel-zinc cell which has (1) a nickel-nickel hydroxide cathode; (2) a zinc-zinc oxide anode containing (A) a corrosion inhibitor such as PBO, SNO2, Tl2O3, in(OH)3 or mixtures thereof; (B) a slight corrosion accelerator such as cdo, bi2o3, ga2o3, or mixtures thereof; and (C) a zinc active material; (3) a mass-transport separator; (4) an alkaline electrolyte; and (5) means for charging the cell with an interrupted current having a frequency of from more than zero to 16 hertz with a rest period of not less than 60 milliseconds. Another desirable feature is the use of a pressure-cutoff switch tomore » terminate charging when the internal pressure of the cell reaches a selected value in the range of from 5 to 8 psig.« less

  5. Factors influencing zinc status of apparently healthy indians.

    PubMed

    Agte, Vaishali V; Chiplonkar, Shashi A; Tarwadi, Kirtan V

    2005-10-01

    To identify dietary, environmental and socio-economic factors associated with mild zinc deficiency, three zinc status indices; erythrocyte membrane zinc (RBCMZn), plasma zinc and super oxide dismutase (SOD) were assessed in free living and apparently healthy Indian population. Dietary patterns of 232 men and 223 women (20-65 yr) from rural, industrial and urban regions of Western India were evaluated by food frequency questionnaire. RBCMZn was estimated using atomic absorption spectrometry, hemoglobin and serum ceruloplasmin by spectrophotometer. On a sub sample (48 men and 51 women) plasma zinc and SOD were also assessed. Mean RBCMZn was 0.5 +/- 0.1 micromols/g protein with 46% individuals showing zinc deficiency. Mean plasma zinc was 0.98 +/- 0.12 microg/mL with 25% men and 2.5% women having values below normal range. Mean SOD was 0.97 +/- 0.1 (u/mL cells). A significant positive correlation was observed between intakes of green leafy vegetables, other vegetables and milk products with RBCMZn status (p < 0.05). But these were not correlated with plasma zinc (p > 0.2). Cereal and legume intakes were negatively correlated with RBCMZn (p < 0.05) but positively correlated with plasma zinc (p < 0.05) and not correlated with SOD (p > 0.2). Fruit and other vegetable intake were positively correlated with SOD (p < 0.05) alone. Logistic regression analyses revealed that RBCMZn was positively associated with intakes of beta-carotene, zinc and environmental conditions and negatively associated with family size (p < 0.05). Plasma zinc indicated positive association with zinc, thiamin and riboflavin intakes (p < 0.05) and SOD showed negative association with iron and family size. RBCMZn was a more sensitive indicator of long-term zinc status than plasma zinc and SOD. Prominent determinants of zinc status were intakes of beta-carotene and zinc along with environmental conditions and family size.

  6. Multi-modular, tris(triphenylamine) zinc porphyrin-zinc phthalocyanine-fullerene conjugate as a broadband capturing, charge stabilizing, photosynthetic 'antenna-reaction center' mimic.

    PubMed

    Kc, Chandra B; Lim, Gary N; D'Souza, Francis

    2015-04-21

    A broadband capturing, charge stabilizing, photosynthetic antenna-reaction center model compound has been newly synthesized and characterized. The model compound is comprised of a zinc porphyrin covalently linked to three units of triphenylamine entities and a zinc phthalocyanine entity. The absorption and fluorescence spectra of zinc porphyrin complemented that of zinc phthalocyanine offering broadband coverage. Stepwise energy transfer from singlet excited triphenylamine to zinc porphyrin, and singlet excited zinc porphyrin to zinc phthalocyanine (kENT ∼ 10(11) s(-1)) was established from spectroscopic and time-resolved transient absorption techniques. Next, an electron acceptor, fullerene was introduced via metal-ligand axial coordination to both zinc porphyrin and zinc phthalocyanine centers, and they were characterized by spectroscopic and electrochemical techniques. An association constant of 4.9 × 10(4) M(-1) for phenylimidazole functionalized fullerene binding to zinc porphyrin, and 5.1 × 10(4) M(-1) for it binding to zinc phthalocyanine was obtained. An energy level diagram for the occurrence of different photochemical events within the multi-modular donor-acceptor conjugate was established from spectral and electrochemical data. Unlike the previous zinc porphyrin-zinc phthalocyanine-fullerene conjugates, the newly assembled donor-acceptor conjugate has been shown to undergo the much anticipated initial charge separation from singlet excited zinc porphyrin to the coordinated fullerene followed by a hole shift process to zinc phthalocyanine resulting in a long-lived charge separated state as revealed by femto- and nanosecond transient absorption spectroscopic techniques. The lifetime of the final charge separated state was about 100 ns.

  7. Prediction of Serum Zinc Levels in Mexican Children at 2 Years of Age Using a Food Frequency Questionnaire and Different Zinc Bioavailability Criteria

    PubMed Central

    Cantoral, Alejandra; Téllez-Rojo, Martha; Shamah-Levy, Teresa; Schnaas, Lourdes; Hernández-Ávila, Mauricio; Peterson, Karen; Ettinger, Adrienne

    2017-01-01

    Background The 2006 Mexican National Health and Nutrition Survey documented a prevalence of zinc deficiency of almost 30% in children aged one to two years old. Objective We sought to validate a Food Frequency Questionnaire (FFQ) for quantifying dietary bioavailable zinc intake in two-year old Mexican children accounting for phytic acid intake and using serum zinc as a reference. Methods This cross-sectional study was nested within a longitudinal birth cohort of 333 young children in Mexico City. Non-fasting serum zinc concentration was measured and dietary zinc intake was calculated on the basis of a semi-quantitative FFQ administered to their mothers. The relationship between dietary zinc intake and serum zinc was assessed using linear regression, adjusting for phytic acid intake, and analyzed according to two distinct international criteria to estimate bioavailable zinc. Models were stratified by zinc deficiency status. Results Dietary zinc, adjusted for phytic acid intake, explained the greatest proportion of the variance of serum zinc. For each mg of dietary zinc intake, serum zinc increased on average by 0.95 μg/dL (0.15 μmol/L) (p=0.06). When stratified by zinc status, this increase was 0.74 μg/dL (p=0.12) for each milligram of zinc consumed among children with adequate serum zinc (N=276) whereas among those children with zinc deficiency (N=57), serum zinc increased by only 0.11 μg/dL (p=0.82). Conclusion A semi-quantitative FFQ can be used for predicting serum zinc in relation to dietary intake in young children, particularly among those who are zinc-replete, and when phytic acid/phytate intake is considered. Future studies should be conducted accounting for both zinc status and dietary zinc inhibitors to further elucidate and validate these findings. PMID:26121697

  8. In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

    NASA Astrophysics Data System (ADS)

    Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

    1993-10-01

    The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

  9. Zinc and the modulation of redox homeostasis

    PubMed Central

    Oteiza, Patricia I.

    2012-01-01

    Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

  10. The Application of Lean Thinking Principles and Kaizen Practices for the Successful Development and Implementation of the Ares I-X Flight Test Rocket and Mission

    NASA Technical Reports Server (NTRS)

    Askins, B. R.; Davis, S. R.; Heitzman, K. S.; Olsen, R. A.

    2011-01-01

    On October 28, 2009 the Ares I-X flight test rocket launched from Kennedy Space Center and flew its suborbital trajectory as designed. The mission was successfully completed as data from the test, and associated development activities were analyzed, transferred to stakeholders, and well documented. A positive lesson learned from Ares I-X was that the application of lean thinking principles and kaizen practices was very effective in streamlining development activities. Ares I-X, like other historical rocket development projects, was hampered by technical, cost, and schedule challenges and if not addressed boldly could have resulted in cancellation of the test. The mission management team conducted nine major meetings, referred to as lean events, across its elements to assess plans, procedures, processes, requirements, controls, culture, organization, use of resources, and anything that could be changed to optimize schedule or reduce risk. The preeminent aspect of the lean events was the focus on value added activities and the removal or at least reduction in non-value added activities. Trained Lean Six Sigma facilitators assisted the Ares I-X developers in conducting the lean events. They indirectly helped formulate the mission s own unique methodology for assessing schedule. A core team was selected to lead the events and report to the mission manager. Each activity leveraged specialized participants to analyze the subject matter and its related processes and then recommended alternatives and solutions. Stakeholders were the event champions. They empowered and encouraged the team to succeed. The keys to success were thorough preparation, honest dialog, small groups, adherence to the Ares I-X ground rules, and accountability through disciplined reporting and tracking of actions. This lean event formula was game-changing as demonstrated by Ares I-X. It is highly recommended as a management tool to help develop other complex systems efficiently. The key benefits for

  11. The Application of Lean Thinking Principles and Kaizen Practices for the Successful Development and Implementation of the Ares I-X Flight Test Rocket and Mission

    NASA Technical Reports Server (NTRS)

    Askins, B. R.; Davis, S. R.; Heitzman, K. S.; Olsen, R. A.

    2011-01-01

    On October 28, 2009 the Ares I-X flight test rocket launched from Kennedy Space Center and flew its suborbital trajectory as designed. The mission was successfully completed as data from the test, and associated development activities were analyzed, transferred to stakeholders, and well documented. Positive lessons learned from Ares I-X were that the application of lean thinking principles and kaizen practices are effective in streamlining development activities. Ares I-X, like other historical rocket development projects, was hampered by technical, cost, and schedule challenges and if not addressed boldly could have resulted in cancellation of the test. The mission management team conducted nine major meetings, referred to as lean events, across its elements to assess plans, procedures, processes, requirements, controls, culture, organization, use of resources, and anything that could be changed to optimize schedule or reduce risk. The preeminent aspect of the lean events was the focus on value added activities and the removal or at least reduction in non-value activities. Trained Lean Six Sigma facilitators assisted the Ares I-X developers in conducting the lean events. They indirectly helped formulate the mission s own unique methodology for assessing schedule. A core team was selected to lead the events and report to the mission manager. Each activity leveraged specialized participants to analyze the subject matter and its related processes and then recommended alternatives and solutions. Stakeholders were the event champions. They empowered and encouraged the team to succeed. The keys to success were thorough preparation, honest dialog, small groups, adherence to the Ares I-X ground rules, and accountability through disciplined reporting and tracking of actions. This lean event formula was game-changing as demonstrated by the success of Ares I-X. It is highly recommended as a management tool to help develop other complex systems efficiently. The key benefits

  12. 21 CFR 172.399 - Zinc methionine sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc methionine sulfate. 172.399 Section 172.399... CONSUMPTION Special Dietary and Nutritional Additives § 172.399 Zinc methionine sulfate. Zinc methionine... conditions: (a) The additive is the product of the reaction between equimolar amounts of zinc sulfate and DL...

  13. Process for preparing zinc oxide-based sorbents

    DOEpatents

    Gangwal, Santosh Kumar [Cary, NC; Turk, Brian Scott [Durham, NC; Gupta, Raghubir Prasad [Durham, NC

    2011-06-07

    The disclosure relates to zinc oxide-based sorbents, and processes for preparing and using them. The sorbents are preferably used to remove one or more reduced sulfur species from gas streams. The sorbents comprise an active zinc component, optionally in combination with one or more promoter components and/or one or more substantially inert components. The active zinc component is a two phase material, consisting essentially of a zinc oxide (ZnO) phase and a zinc aluminate (ZnAl.sub.2O.sub.4) phase. Each of the two phases is characterized by a relatively small crystallite size of typically less than about 500 Angstroms. Preferably the sorbents are prepared by converting a precursor mixture, comprising a precipitated zinc oxide precursor and a precipitated aluminum oxide precursor, to the two-phase, active zinc oxide containing component.

  14. Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

    PubMed

    D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

    2017-12-01

    A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

  15. Pseudomonas aeruginosa Trent and zinc homeostasis.

    PubMed

    Davies, Corey B; Harrison, Mark D; Huygens, Flavia

    2017-09-01

    Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Ares I-X Range Safety Simulation Verification and Analysis Independent Validation and Verification

    NASA Technical Reports Server (NTRS)

    Merry, Carl M.; Tarpley, Ashley F.; Craig, A. Scott; Tartabini, Paul V.; Brewer, Joan D.; Davis, Jerel G.; Dulski, Matthew B.; Gimenez, Adrian; Barron, M. Kyle

    2011-01-01

    NASA s Ares I-X vehicle launched on a suborbital test flight from the Eastern Range in Florida on October 28, 2009. To obtain approval for launch, a range safety final flight data package was generated to meet the data requirements defined in the Air Force Space Command Manual 91-710 Volume 2. The delivery included products such as a nominal trajectory, trajectory envelopes, stage disposal data and footprints, and a malfunction turn analysis. The Air Force s 45th Space Wing uses these products to ensure public and launch area safety. Due to the criticality of these data, an independent validation and verification effort was undertaken to ensure data quality and adherence to requirements. As a result, the product package was delivered with the confidence that independent organizations using separate simulation software generated data to meet the range requirements and yielded consistent results. This document captures Ares I-X final flight data package verification and validation analysis, including the methodology used to validate and verify simulation inputs, execution, and results and presents lessons learned during the process

  17. Changes in zinc status and zinc transporters expression in whole blood of patients with Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Florea, Daniela; Molina-López, Jorge; Hogstrand, Christer; Lengyel, Imre; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Planells, Elena

    2018-09-01

    Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of many nutrients and especially zinc, depleting their body reserves. This study was designed to assess the zinc status in critical care patients with systemic inflammatory response syndrome (SIRS), comparing them with a group of healthy people, and studying the association with expression of zinc transporters. This investigation was a prospective, multicentre, comparative, observational and analytic study. Twelve critically ill patients from different hospitals and 12 healthy subjects from Granada, Spain, all with informed consent were recruited. Data on daily nutritional assessment, ICU severity scores, inflammation, clinical and nutritional parameters, plasma and blood cell zinc concentrations, and levels of transcripts for zinc transporters in whole blood were taken at admission and at the seventh day of the ICU stay. Zinc levels on critical ill patient are diminish comparing with the healthy control (HS: 0.94 ± 0.19; CIPF: 0.67 ± 0.16 mg/dL). The 58% of critical ill patients showed zinc plasma deficiency at beginning of study while 50.0% of critical ill after 7 days of ICU stay. ZnT7, ZIP4 and ZIP9 were the zinc transporters with highest expression in whole blood. In general, all zinc transporters were significantly down-regulated (P < 0.05) in the critical ill population at admission in comparison with healthy subjects. Severity scores and inflammation were significantly associated (P < 0.05) with zinc plasma levels, and zinc transporters ZIP3, ZIP4, ZIP8, ZnT6, ZnT7. Expression of 11 out of 24 zinc transporters was analysed, and ZnT1, ZnT4, ZnT5 and ZIP4, which were downregulated by more than 3-fold in whole blood of patients. In summary, in our study an alteration of zinc status was related with the severity-of-illness scores and inflammation in critical ill patients since admission in ICU stay. SIRS

  18. Maternal Zinc Intakes and Homeostatic Adjustments during Pregnancy and Lactation

    PubMed Central

    Donangelo, Carmen Marino; King, Janet C.

    2012-01-01

    Zinc plays critical roles during embryogenesis, fetal growth, and milk secretion, which increase the zinc need for pregnancy and lactation. Increased needs can be met by increasing the dietary zinc intake, along with making homeostatic adjustments in zinc utilization. Potential homeostatic adjustments include changes in circulating zinc, increased zinc absorption, decreased zinc losses, and changes in whole body zinc kinetics. Although severe zinc deficiency during pregnancy has devastating effects, systematic reviews and meta-analysis of the effect of maternal zinc supplementation on pregnancy outcomes have consistently shown a limited benefit. We hypothesize, therefore, that zinc homeostatic adjustments during pregnancy and lactation improve zinc utilization sufficiently to provide the increased zinc needs in these stages and, therefore, mitigate immediate detrimental effects due to a low zinc intake. The specific questions addressed are the following: How is zinc utilization altered during pregnancy and lactation? Are those homeostatic adjustments influenced by maternal zinc status, dietary zinc, or zinc supplementation? These questions are addressed by critically reviewing results from published human studies on zinc homeostasis during pregnancy and lactation carried out in different populations worldwide. PMID:22852063

  19. Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

    PubMed

    Cho, Minsu; Hu, Guanggan; Caza, Mélissa; Horianopoulos, Linda C; Kronstad, James W; Jung, Won Hee

    2018-01-01

    Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

  20. High performance zinc anode for battery applications

    NASA Technical Reports Server (NTRS)

    Casey, John E., Jr. (Inventor)

    1998-01-01

    An improved zinc anode for use in a high density rechargeable alkaline battery is disclosed. A process for making the zinc electrode comprises electrolytic loading of the zinc active material from a slightly acidic zinc nitrate solution into a substrate of nickel, copper or silver. The substrate comprises a sintered plaque having very fine pores, a high surface area, and 80-85 percent total initial porosity. The residual porosity after zinc loading is approximately 25-30%. The electrode of the present invention exhibits reduced zinc mobility, shape change and distortion, and demonstrates reduced dendrite buildup cycling of the battery. The disclosed battery is useful for applications requiring high energy density and multiple charge capability.

  1. Zinc Regulation of Aminopeptidase B Involved in Neuropeptide Production

    PubMed Central

    Hwang, Shin-Rong; Hook, Vivian

    2009-01-01

    Aminopeptidase B (AP-B) is a metallopeptidase that removes basic residues from the N-termini of neuropeptide substrates in secretory vesicles. This study assessed zinc regulation of AP-B activity, since secretory vesicles contain endogenous zinc. AP-B was inhibited by zinc at concentrations typically present in secretory vesicles. Zinc effects were dependent on concentration, incubation time, and the molar ratio of zinc to enzyme. AP-B activity was recovered upon removal of zinc. AP-B with zinc became susceptible to degradation by trypsin, suggesting that zinc alters enzyme conformation. Zinc regulation demonstrates the metallopeptidase property of AP-B. PMID:18571504

  2. Method for the regeneration of spent molten zinc chloride

    DOEpatents

    Zielke, Clyde W.; Rosenhoover, William A.

    1981-01-01

    In a process for regenerating spent molten zinc chloride which has been used in the hydrocracking of coal or ash-containing polynuclear aromatic hydrocarbonaceous materials derived therefrom and which contains zinc chloride, zinc oxide, zinc oxide complexes and ash-containing carbonaceous residue, by incinerating the spent molten zinc chloride to vaporize the zinc chloride for subsequent condensation to produce a purified molten zinc chloride: an improvement comprising the use of clay in the incineration zone to suppress the vaporization of metals other than zinc. Optionally water is used in conjunction with the clay to further suppress the vaporization of metals other than zinc.

  3. SPITZER IRAC OBSERVATIONS OF IR EXCESS IN HOLMBERG IX X-1: A CIRCUMBINARY DISK OR A VARIABLE JET?

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

    Dudik, R. P.; Berghea, C. T.; Roberts, T. P.

    2016-11-01

    We present Spitzer Infrared Array Camera photometric observations of the ultraluminous X-ray source (ULX, X-1) in Holmberg IX. We construct a spectral energy distribution (SED) for Holmberg IX X-1 based on published optical, UV, and X-ray data combined with the IR data from this analysis. We modeled the X-ray and optical data with disk and stellar models; however, we find a clear IR excess in the ULX SED that cannot be explained by fits or extrapolations of any of these models. Instead, further analysis suggests that the IR excess results from dust emission, possibly a circumbinary disk, or a variablemore » jet.« less

  4. Serum zinc, copper, retinol-binding protein, prealbumin, and ceruloplasmin concentrations in infants receiving intravenous zinc and copper supplementation.

    PubMed

    Lockitch, G; Godolphin, W; Pendray, M R; Riddell, D; Quigley, G

    1983-02-01

    One hundred twenty-seven newborn infants requiring parenteral nutrition were randomly assigned to receive differing amounts of zinc (40 to 400 micrograms/kg/day) and copper (20 or 40 micrograms/kg/day) supplementation within five birth weight groups (600 to 2,500 gm). The serum zinc concentration remained relatively constant in the group receiving the most zinc supplementation after two weeks of therapy, but declined sharply in the groups receiving less supplementation. No effect of increased copper intake was noted on ceruloplasmin values, but a difference in serum copper concentrations was noted at two weeks. No correlation was noted between serum zinc and copper values or among those for serum zinc, retinol-binding protein, and prealbumin. Reference ranges were defined for serum zinc, copper, retinol-binding protein, prealbumin, and ceruloplasmin in the preterm infant.

  5. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... amounts consistent with good manufacturing practice. (d) Labeling. The color additive and any mixtues... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc...). It is principally composed of Zn. (2) Color additive mixtures for drug use made with zinc oxide may...

  6. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc gluconate. 182.8988 Section 182.8988 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b...

  7. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from...

  8. 21 CFR 182.8997 - Zinc sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc sulfate. 182.8997 Section 182.8997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of...

  9. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions...

  10. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use. This...

  11. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use. This...

  12. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc gluconate. 182.8988 Section 182.8988 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is generally recognized as safe when used...

  13. 21 CFR 182.8988 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc gluconate. 182.8988 Section 182.8988 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8988 Zinc gluconate. (a) Product. Zinc gluconate. (b) Conditions of use. This substance is generally recognized as safe when used...

  14. Zinc activates damage-sensing TRPA1 ion channels.

    PubMed

    Hu, Hongzhen; Bandell, Michael; Petrus, Matt J; Zhu, Michael X; Patapoutian, Ardem

    2009-03-01

    Zinc is an essential biological trace element. It is required for the structure or function of over 300 proteins, and it is increasingly recognized for its role in cell signaling. However, high concentrations of zinc have cytotoxic effects, and overexposure to zinc can cause pain and inflammation through unknown mechanisms. Here we show that zinc excites nociceptive somatosensory neurons and causes nociception in mice through TRPA1, a cation channel previously shown to mediate the pungency of wasabi and cinnamon through cysteine modification. Zinc activates TRPA1 through a unique mechanism that requires zinc influx through TRPA1 channels and subsequent activation via specific intracellular cysteine and histidine residues. TRPA1 is highly sensitive to intracellular zinc, as low nanomolar concentrations activate TRPA1 and modulate its sensitivity. These findings identify TRPA1 as an important target for the sensory effects of zinc and support an emerging role for zinc as a signaling molecule that can modulate sensory transmission.

  15. Biomarkers of Nutrition for Development (BOND)—Zinc Review12345

    PubMed Central

    King, Janet C; Brown, Kenneth H; Gibson, Rosalind S; Krebs, Nancy F; Lowe, Nicola M; Siekmann, Jonathan H; Raiten, Daniel J

    2016-01-01

    Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes

  16. Photoluminescence of cerium fluoride and cerium-doped lanthanum fluoride nanoparticles and investigation of energy transfer to photosensitizer molecules.

    PubMed

    Cooper, Daniel R; Kudinov, Konstantin; Tyagi, Pooja; Hill, Colin K; Bradforth, Stephen E; Nadeau, Jay L

    2014-06-28

    CexLa1-xF3 nanoparticles have been proposed for use in nanoscintillator-photosensitizer systems, where excitation of nanoparticles by ionizing radiation would result in energy transfer to photosensitizer molecules, effectively combining the effects of radiotherapy and photodynamic therapy. Thus far, there have been few experimental investigations of such systems. This study reports novel synthesis methods for water-dispersible Ce0.1La0.9F3/LaF3 and CeF3/LaF3 core/shell nanoparticles and an investigation of energy transfer to photosensitizers. Unbound deuteroporphyrin IX 2,4-disulfonic acid was found to substantially quench the luminescence of large (>10 nm diameter) aminocaproic acid-stabilized nanoparticles at reasonable concentrations and loading amounts: up to 80% quenching at 6% w/w photosensitizer loading. Energy transfer was found to occur primarily through a cascade, with excitation of "regular" site Ce(3+) at 252 nm relayed to photosensitizer molecules at the nanoparticle surface through intermediate "perturbed" Ce(3+) sites. Smaller (<5 nm) citrate-stabilized nanoparticles were coated with the bisphosphonate alendronate, allowing covalent conjugation to chlorin e6 and resulting in static quenching of the nanoparticle luminescence: ∼50% at ∼0.44% w/w. These results provide insight into energy transfer mechanisms that may prove valuable for optimizing similar systems.

  17. Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines

    PubMed Central

    Caughey, Winslow S.; Raymond, Lynne D.; Horiuchi, Motohiro; Caughey, Byron

    1998-01-01

    A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC50 values of 0.5–1 μM in scrapie-infected mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects on protein biosynthesis in general or PrP-sen biosynthesis in particular. Tetrapyrroles also inhibited PrP-res formation in a cell-free reaction composed predominantly of hamster PrP-res and PrP-sen. Inhibitors were found among phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples included compounds containing anionic, neutral protic, and cationic peripheral substituents and various metals. We conclude that certain tetrapyrroles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects. The inhibition observed in the cell-free conversion reaction suggests that the mechanism involved direct interactions of the tetrapyrrole with PrP-res and/or PrP-sen. These findings introduce a new class of inhibitors of PrP-res formation that represents a potential source of therapeutic agents for transmissible spongiform encephalopathies. PMID:9770449

  18. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  19. 21 CFR 582.5997 - Zinc sulfate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

  20. 21 CFR 182.8991 - Zinc oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc oxide. 182.8991 Section 182.8991 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8991 Zinc oxide. (a) Product. Zinc oxide. (b) Conditions of use...

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