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Sample records for licence ix 354c

  1. Genome-Wide Association Study Identifies ZNF354C Variants Associated with Depression from Interferon-Based Therapy for Chronic Hepatitis C

    PubMed Central

    Matsunami, Kayoko; Nishida, Nao; Kaneko, Naoko; Ikeo, Kazuho; Toyo-oka, Licht; Takeuchi, Hiroshi; Matsuura, Kentaro; Tamori, Akihiro; Nomura, Hideyuki; Yoshiji, Hitoshi; Imamura, Masatoshi; Masaki, Naohiko; Hayakawa, Tatsuro; Ide, Tatsuya; Shimada, Noritomo; Ikeda, Fusao; Hino, Keisuke; Nishiguchi, Shuhei; Okuse, Chiaki; Nojiri, Shunsuke; Sawamoto, Kazunobu; Tokunaga, Katsushi; Joh, Takashi; Tanaka, Yasuhito

    2016-01-01

    The therapeutic use of interferon (IFN) is known to cause depression that frequently interrupts treatment. To identify genetic variants associated with IFN-induced depression, we conducted a genome-wide association study (GWAS) of 224 Japanese chronic hepatitis C patients receiving IFN-based therapy in a multicenter prospective study and stratified them into two groups according to the Beck Depression Inventory, Second Edition (BDI-II) score. In the GWAS stage, we selected 42 candidate single nucleotide polymorphisms (SNPs) to perform replication analysis in an independent set of 160 subjects. The SNP rs1863918 in strong linkage disequilibrium with SNPs located around the Zinc finger 354C (ZNF354C) gene on chromosome 5 showed a significant association when the results of GWAS and replication were combined (odds ratio = 2.55, P = 7.89×10−8 in the allele frequency model), suggesting that the rs1863918 T allele was associated with IFN-induced depression. Furthermore, logistic regression analysis showed that rs1863918 T allele, a history of depression, and younger age were independent predictive factors for IFN-induced depression. Interestingly, western blotting and immunofluorescence showed that ZNF354C was highly expressed in the hippocampus in mice, a region implicated in the pathology of psychiatric symptoms. In conclusion, we identified rs1863918 as significantly associated with IFN-induced depression, and revealed that the candidate gene ZNF354C is highly expressed in the hippocampus of mice. Our data might be useful for elucidating the pathogenic mechanisms of depression induced by drugs including IFN. PMID:27723809

  2. Licencing and Training Reform in the Australian Aircraft Maintenance Industry

    ERIC Educational Resources Information Center

    Hampson, Ian; Fraser, Doug

    2016-01-01

    The training and licencing of aircraft maintenance engineers fulfils a crucial protective function since it is they who perform and supervise aircraft maintenance and certify that planes are safe afterwards. In Australia, prior to training reform, a trades-based system of aircraft maintenance engineer training existed in an orderly relation with…

  3. Licence to Kill: About Accreditation Issues and James Bond

    ERIC Educational Resources Information Center

    Scheele, Ko

    2004-01-01

    Accreditation has become something of a hot topic in higher education. In Europe it has been described as a 'Licence to Kill'. The James Bond metaphor is particularly illustrative when reflecting on quality assurance challenges in higher education. Publications on this subject in recent years reveal that the array of issues associated with…

  4. Volunteer Voice. Volume IX.

    ERIC Educational Resources Information Center

    Volunteer Voice, 1992

    1992-01-01

    This document consists of the three volume IX issues of "Volunteer Voice," a newsletter of the Tacoma Community House Training Project. The first issue consists of one teacher's personal account of English-as-a-Second-Language (ESL) teaching and includes the following: an annotated list of ESL text books, a list of activities resources,…

  5. Title IX: Boom or Bust?

    ERIC Educational Resources Information Center

    Mather, Marilyn J.

    2003-01-01

    Athletics has been significantly impacted by Title IX through an increase the number of female athletes, the number of teams available, and indirectly, the development of women's professional leagues. However, women in leadership positions in athletics have declined significantly since Title IX was signed into law. A concern about the…

  6. The social licence for research: why care.data ran into trouble.

    PubMed

    Carter, Pam; Laurie, Graeme T; Dixon-Woods, Mary

    2015-05-01

    In this article we draw on the concept of a social licence to explain public concern at the introduction of care.data, a recent English initiative designed to extract data from primary care medical records for commissioning and other purposes, including research. The concept of a social licence describes how the expectations of society regarding some activities may go beyond compliance with the requirements of formal regulation; those who do not fulfil the conditions for the social licence (even if formally compliant) may experience ongoing challenge and contestation. Previous work suggests that people's cooperation with specific research studies depends on their perceptions that their participation is voluntary and is governed by values of reciprocity, non-exploitation and service of the public good. When these conditions are not seen to obtain, threats to the social licence for research may emerge. We propose that care.data failed to adequately secure a social licence because of: (i) defects in the warrants of trust provided for care.data, (ii) the implied rupture in the traditional role, expectations and duties of general practitioners, and (iii) uncertainty about the status of care.data as a public good. The concept of a social licence may be useful in explaining the specifics of care.data, and also in reinforcing the more general lesson for policy-makers that legal authority does not necessarily command social legitimacy.

  7. The social licence for research: why care.data ran into trouble

    PubMed Central

    Carter, Pam; Laurie, Graeme T; Dixon-Woods, Mary

    2015-01-01

    In this article we draw on the concept of a social licence to explain public concern at the introduction of care.data, a recent English initiative designed to extract data from primary care medical records for commissioning and other purposes, including research. The concept of a social licence describes how the expectations of society regarding some activities may go beyond compliance with the requirements of formal regulation; those who do not fulfil the conditions for the social licence (even if formally compliant) may experience ongoing challenge and contestation. Previous work suggests that people's cooperation with specific research studies depends on their perceptions that their participation is voluntary and is governed by values of reciprocity, non-exploitation and service of the public good. When these conditions are not seen to obtain, threats to the social licence for research may emerge. We propose that care.data failed to adequately secure a social licence because of: (i) defects in the warrants of trust provided for care.data, (ii) the implied rupture in the traditional role, expectations and duties of general practitioners, and (iii) uncertainty about the status of care.data as a public good. The concept of a social licence may be useful in explaining the specifics of care.data, and also in reinforcing the more general lesson for policy-makers that legal authority does not necessarily command social legitimacy. PMID:25617016

  8. Enzymic conversion of alpha-oxyprotohaem IX into biliverdin IX alpha by haem oxygenase.

    PubMed Central

    Yoshinaga, T; Sudo, Y; Sano, S

    1990-01-01

    Conversion of four isomers of meso-oxyprotohaem IX into the corresponding biliverdin IX was attempted with a reconstituted haem oxygenase system in the presence of NADPH-cytochrome c reductase and NADPH. Only the alpha-isomer of meso-oxyprotohaem IX was converted effectively into biliverdin IX alpha, which was further reduced to bilirubin IX alpha by biliverdin reductase. Only trace amounts of biliverdins IX beta, IX gamma and IX delta were respectively formed from the incubation mixture of the corresponding oxyprotohaemin IX isomers with the complete haem oxygenase system under the same conditions. In a kinetic study, the Km for alpha-meso-oxyprotohaem IX was 3.6 microM, which was 2-fold higher than that for protohaem IX. The maximum velocity (Vmax.) of the conversion of alpha-meso-oxyprotohaem IX into biliverdin IX alpha was twice as fast as that of protohaem IX. These results demonstrate that alpha-meso-oxyprotohaem IX is an intermediate of haem degradation and it was converted stereospecifically into biliverdin IX alpha via verdohaem IX alpha. PMID:2122884

  9. 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…

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

    PubMed

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

    1978-11-01

    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.

  11. A European Computer Driving Licence: Integrating Computer Literacy in the New Social Work Degree

    ERIC Educational Resources Information Center

    Gregor, Claire

    2008-01-01

    "Informacy", the learning of information technology skills, is now a key element of all Social Work curricula in the U.K. following the General Social Care Council's accreditation requirements. These stipulate that all undergraduates acquire computer literacy skills to the level of the European Computer Driving Licence (ECDL) or its equivalence…

  12. Title IX: A Brief History. 25 Years of Title IX. WEEA Digest.

    ERIC Educational Resources Information Center

    Valentin, Iram

    This brief history of Title IX points out that the role of women and girls in education and the work force began to change significantly with the passage of Title IX as part of the Education Amendments to the Civil Rights Act of 1964. Title IX ensures legal protection against discrimination for students and employees. This article discusses the…

  13. 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 [ ]....

  14. 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 procedures. Pt. 86, Index Subject Index to Title IX Preamble...

  15. 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 [ ]....

  16. 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... to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets . A Access...

  17. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  18. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  19. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  20. 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 procedures. Pt. 86, Index Subject Index to Title IX Preamble...

  1. 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.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1 Preamble paragraph numbers...

  2. 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..., Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  3. 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... to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets . A Access...

  4. 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...

  5. 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..., Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  6. 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..., Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

  7. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  8. 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... to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets . A Access...

  9. 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.... Pt. 86, 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

    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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  11. 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...

  12. 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

    ... 34 Education 1 2004-07-01 2004-07-01 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  13. 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... to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets . A Access...

  14. 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 procedures. Pt. 86, Index Subject Index to Title IX Preamble...

  15. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  16. 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 procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1...

  17. 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.... Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are...

  18. Statistical Evidence and Compliance with Title IX

    ERIC Educational Resources Information Center

    Cheslock, John J.; Eckes, Suzanne E.

    2008-01-01

    The scope of Title IX clearly includes all aspects of education, but the legislation's application to college athletics receives the most attention. Athletics programs, unlike most academic activities, are sex segregated, so the proper interpretation of the intercollegiate athletics provisions of Title IX is less clear-cut. This article examines…

  19. Title IX and Sex Discrimination. Revised.

    ERIC Educational Resources Information Center

    Office for Civil Rights (ED), Washington, DC.

    Title IX of the Education Amendments of 1972 protects people from discrimination based on sex in education programs or activities that receive Federal financial assistance. This brochure outlines the responsibilities of education programs and activities covered by Title IX, the responsibilities of the Office for Civil Rights (OCR) in enforcing…

  20. First test of WTO mechanism for procuring generic medicines under compulsory licence, via Canada's Access to Medicines Regime.

    PubMed

    Elliott, Richard

    2007-12-01

    In July 2007, Rwanda became the first nation to initiate use of a procedure under the rules of the World Trade Organization (WTO) that is supposed to let developing countries import lower-cost, generic medicines produced in other countries under compulsory licences. And two months later, based on Rwanda's initiative, Canada's Commissioner of Patents issued the first compulsory licence under this system to permit the production of a patented AIDS drug to that country.

  1. Immunologic studies of factor IX (Christmas factor). II. Immunoradiometric assay of factor IX antigen.

    PubMed

    Yang, H C

    1978-06-01

    A solid-phase two-site immunoradiometric assay has been developed which measures factor IX antigen levels as low as 0.0004 u per ml of plasma. In normal individuals, the factor IX antigen level correlated with the factor IX procoagulant level. In haemophilia B, 14 patients had markedly reduced antigen levels (less than 0.06 u/ml) and five had normal levels (greater than 0.60 u/ml).

  2. El Titulo IX y La Discriminacion por Sexo (Title IX and Sex Discrimination).

    ERIC Educational Resources Information Center

    Office for Civil Rights (ED), Washington, DC.

    Title IX of the Education Amendments of 1972 protects people from discrimination based on sex in education programs or activities that receive Federal financial assistance. This brochure outlines the responsibilities of education programs and activities covered by Title IX, the responsibilities of the Office for Civil Rights (OCR) in enforcing…

  3. Quantum supersymmetric Bianchi IX cosmology

    NASA Astrophysics Data System (ADS)

    Damour, Thibault; Spindel, Philippe

    2014-11-01

    We study the quantum dynamics of a supersymmetric squashed three-sphere by dimensionally reducing (to one timelike dimension) the action of D =4 simple supergravity for a S U (2 ) -homogeneous (Bianchi IX) cosmological model. The quantization of the homogeneous gravitino field leads to a 64-dimensional fermionic Hilbert space. After imposition of the diffeomorphism constraints, the wave function of the Universe becomes a 64-component spinor of spin(8,4) depending on the three squashing parameters, which satisfies Dirac-like, and Klein-Gordon-like, wave equations describing the propagation of a "quantum spinning particle" reflecting off spin-dependent potential walls. The algebra of the supersymmetry constraints and of the Hamiltonian one is found to close. One finds that the quantum Hamiltonian is built from operators that generate a 64-dimensional representation of the (infinite-dimensional) maximally compact subalgebra of the rank-3 hyperbolic Kac-Moody algebra A E3 . The (quartic-in-fermions) squared-mass term μ^ 2 entering the Klein-Gordon-like equation has several remarkable properties: (i) it commutes with all the other (Kac-Moody-related) building blocks of the Hamiltonian; (ii) it is a quadratic function of the fermion number NF; and (iii) it is negative in most of the Hilbert space. The latter property leads to a possible quantum avoidance of the singularity ("cosmological bounce"), and suggests imposing the boundary condition that the wave function of the Universe vanish when the volume of space tends to zero (a type of boundary condition which looks like a final-state condition when considering the big crunch inside a black hole). The space of solutions is a mixture of "discrete-spectrum states" (parametrized by a few constant parameters, and known in explicit form) and of continuous-spectrum states (parametrized by arbitrary functions entering some initial-value problem). The predominantly negative values of the squared-mass term lead to a "bottle

  4. 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…

  5. 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 committee lacking…

  6. 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.

  7. The European computer driving licence and the use of computers by dental students.

    PubMed

    Antonarakis, G S

    2009-02-01

    The use of computers within the dental curriculum for students is vital for many aspects of their studies. The aim of this study was to assess how dental students who had obtained the European computer driving licence (ECDL) qualification (an internationally-recognised standard of competence) through taught courses, felt about the qualification, and how it changed their habits vis-à-vis computers, and information and communication technology. This study was carried out as a descriptive, one-off, cross-sectional survey. A questionnaire was distributed to 100 students who had successfully completed the course, with questions pertaining to the use of email, word processing and Internet for course-works, Medline for research, computer based learning, online lecture notes, and online communication with members of staff, both before and after ECDL qualification. Scaled responses were given. The attitudes of students towards the course were also assessed. The frequencies and percentage distributions of the responses to each question were analysed. It was found that dental students who follow ECDL teaching and successfully complete its requirements, seem to increase the frequency with which they use email, word processing and Internet for course works, Medline for research purposes, computer based learning, online lecture notes, and online communication with staff. Opinions about the ECDL course varied, many dental students finding the course easy, enjoying it only a little, but admitting that it improved their computer skills.

  8. Vehicle impoundments improve drinking and driving licence suspension outcomes: Large-scale evidence from Ontario.

    PubMed

    Byrne, Patrick A; Ma, Tracey; Elzohairy, Yoassry

    2016-10-01

    Although vehicle impoundment has become a common sanction for various driving offences, large-scale evaluations of its effectiveness in preventing drinking and driving recidivism are almost non-existent in the peer-reviewed literature. One reason is that impoundment programs have typically been introduced simultaneously with other countermeasures, rendering it difficult to disentangle any observed effects. Previous studies of impoundment effectiveness conducted when such programs were implemented in isolation have typically been restricted to small jurisdictions, making high-quality evaluation difficult. In contrast, Ontario's "long-term" and "seven-day" impoundment programs were implemented in relative isolation, but with tight relationships to already existing drinking and driving suspensions. In this work, we used offence data produced by Ontario's population of over 9 million licensed drivers to perform interrupted time series analysis on drinking and driving recidivism and on rates of driving while suspended for drinking and driving. Our results demonstrate two key findings: (1) impoundment, or its threat, improves compliance with drinking and driving licence suspensions; and (2) addition of impoundment to suspension reduces drinking and driving recidivism, possibly through enhanced suspension compliance.

  9. Ares I-X 30 Day Report

    NASA Technical Reports Server (NTRS)

    Ess, Bob; Smith, Marshall

    2009-01-01

    This slide presentation represents the 30 day report on the Ares I-X test flight. Included in the review is information on the following areas: (1) Ground Systems, (2) Guidance, Navigation and Control, (3) Roll Response, (4) Vehicle Response, (5) Control System Performance, (6) Structural Damping, (7) Thrust Oscillation, (8) Stage Separation, (9) Connector Assessment, (10) USS Splashdown, (11) Data Recorder and (12) FS Hardware Assessment.

  10. Proteolytic processing of human coagulation factor IX by plasmin.

    PubMed

    Samis, J A; Ramsey, G D; Walker, J B; Nesheim, M E; Giles, A R

    2000-02-01

    Previous studies have shown that thrombin generation in vivo caused a 92% decrease in factor IX (F.IX) activity and the appearance of a cleavage product after immunoblotting that comigrated with activated F.IX (F.IXa). Under these conditions, the fibrinolytic system was clearly activated, suggesting plasmin may have altered F.IX. Thus, the effect(s) of plasmin on human F.IX was determined in vitro. Plasmin (50 nM) decreased the 1-stage clotting activity of F.IX (4 microM) by 80% and the activity of F.IXa (4 microM) by 50% after 30 minutes at 37 degrees C. Plasmin hydrolysis of F.IX yields products of 45, 30, 20, and 14 kd on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2 products of 52 and 14 kd under nonreducing conditions. Plasmin-treated F.IX did not bind the active site probe, p-aminobenzamidine, or form an SDS-stable complex with antithrombin. It only marginally activated human factor X in the presence of phospholipid and activated factor VIII. Although dansyl-Glu-Gly-Arg-chloromethyl ketone inactivated-F. IXa inhibited the clotting activity of F.IXa, plasmin-treated F.IX did not. Plasmin cleaves F.IX after Lys43, Arg145, Arg180, Lys316, and Arg318, but F.IXa is not appreciably generated despite cleavage at the 2 normal activation sites (Arg145 and Arg180). Tissue plasminogen activator-catalyzed lysis of fibrin formed in human plasma results in generation of the 45- and 30-kd fragments of F.IX and decreased F.IX clotting activity. Collectively, the results suggest that plasmin is able to down-regulate coagulation by inactivating F.IX. PMID:10648407

  11. Activation of human factor IX (Christmas factor).

    PubMed

    Di Scipio, R G; Kurachi, K; Davie, E W

    1978-06-01

    Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its

  12. On the mechanism of the chemical and enzymic oxygenations of alpha-oxyprotohemin IX to Fe.biliverdin IX alpha.

    PubMed Central

    Sano, S; Sano, T; Morishima, I; Shiro, Y; Maeda, Y

    1986-01-01

    alpha-Oxyprotohemin IX, an early intermediate in heme catabolism, was synthesized and its autoxidation to biliverdin IX alpha was studied. In anaerobic aqueous pyridine, alpha-oxyprotohemin (hexacoordinated) underwent autoreduction to yield an Fe(II) alpha-oxyprotoporphyrin pi-neutral radical bis(pyridine) complex, which reacted with an equimolar amount of dioxygen to give pyridine.verdohemochrome IX alpha and CO in 75-80% yield via an intermediate with an absorption maximum at 893 nm. Verdohemochrome IX alpha did not react with further dioxygen. Reconstituted apomyoglobin.alpha-oxyprotohemin IX complex (pentacoordinated) reacted with an equimolar amount of dioxygen to form an Fe(II) oxyporphyrin pi-neutral radical intermediate, which rearranged to a green compound (lambda max 660 and 704 nm) with elision of CO. The green product, which is probably an apomyoglobin.verdoheme pi-radical complex, reacted with another equimolar amount of dioxygen to give Fe(III).biliverdin IX alpha. Demetallation of this gave biliverdin IX alpha in overall yield of 70-75%. These results indicate that the sequence of oxyheme autoxidation in the presence of apomyoglobin is alpha-oxyprotoheme IX O2----CO----verdohemochrome IX alpha pi-radical O2----Fe(III).biliverdin IX alpha. A similar mechanism may prevail in vivo. The hexa- and pentacoordinated Fe(II) pi-radical form of the oxyporphyrin is crucial in triggering the autoxidation of the complex to verdohemochrome IX alpha. Further oxygenation of verdohemochrome IX alpha to Fe(III).biliverdin IX alpha occurred only in the pentacoordinated apomyoglobin.verdoheme Fe(II) complex. PMID:3456152

  13. Decreasing number of young licence holders and reduced number of accidents. A description of trends in Sweden.

    PubMed

    Murray, Asa

    2003-11-01

    The following study compares rates of licence holders and rates of car accidents in two age cohorts born in Sweden in 1972 and 1977, respectively. The research material consists of all accidents with injury which these young people have been involved in as car drivers at age 16-21. The periods concerned are 1988-1993 and 1993-1998, respectively. In the respective periods altogether 2082 and 1453 car accidents leading to injury were recorded. The results show a lower rate of licence holders and a lower rate of car accidents in the later age cohort. Particularly the rate of fatal accidents and accidents leading to serious injury was lower. Comparing the earlier with the later age cohort, the reduction of accidents was greatest in the most densely built-up counties of Sweden and in the groups with the highest risk, namely those age and socio-economic groups who had the highest rate of fatalities and accidents leading to serious injury. Factors behind the decrease in the rates of licence holders and the rates of car accidents are discussed. Recession in the economy and less interest in car driving among young people are factors which are suggested as explanations.

  14. 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

    ... 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... obligation, 86.4(b) Form, 86.4(c) Athletics, ; 86.41 Adjustment period, ; 86.41(d) Contact sport defined, 86... responsible employee”, 86.8(a) (b) H Health and Insurance Benefits and Services, ; 86.39, 86.56...

  15. Constitutive episomal expression of polypeptide IX (pIX) in a 293-based cell line complements the deficiency of pIX mutant adenovirus type 5.

    PubMed Central

    Caravokyri, C; Leppard, K N

    1995-01-01

    The human adenovirus type 5 capsid is composed of a number of distinct polypeptides. It has been shown previously that one of these, polypeptide IX (pIX), is not absolutely required for the production of viable virus. However, viruses lacking this polypeptide have a significantly reduced packaging limit and, in the one case studied, also show a thermolabile virion phenotype. This report describes the use of eukaryotic episomal vectors based on the Epstein-Barr virus replicon to generate cells which stably express pIX. These cells provide pIX that is efficiently incorporated into virions that are genetically pIX-; such enhanced thermostability. These cells have also been used to isolate a genetically pIX- virus having a genome of length some 2.3 kbp in excess of the previously defined packaging limit for pIX- virus; the resulting virions have wild-type thermostability. These cells expand the theoretical capacity of adenovirus vectors for foreign DNA to around 9.2 kbp and may therefore be useful in gene therapy applications in which vector capacity is limiting. PMID:7474071

  16. Cranial Nerves IX, X, XI, and XII

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    This article concludes the series on cranial nerves, with review of the final four (IX–XII). To summarize briefly, the most important and common syndrome caused by a disorder of the glossopharyngeal nerve (craniel nerve IX) is glossopharyngeal neuralgia. Also, swallowing function occasionally is compromised in a rare but disabling form of tardive dyskinesia called tardive dystonia, because the upper motor portion of the glossopharyngel nerve projects to the basal ganglia and can be affected by lesions in the basal ganglia. Vagus nerve funtion (craniel nerve X) can be compromised in schizophrenia, bulimia, obesity, and major depression. A cervical lesion to the nerve roots of the spinal accessory nerve (craniel nerve XI) can cause a cervical dystonia, which sometimes is misdiagnosed as a dyskinesia related to neuroleptic use. Finally, unilateral hypoglossal (craniel nerve XII) nerve palsy is one of the most common mononeuropathies caused by brain metastases. Supranuclear lesions of cranial nerve XII are involved in pseudobulbar palsy and ALS, and lower motor neuron lesions of cranial nerve XII can also be present in bulbar palsy and in ALS patients who also have lower motor neuron involvement. This article reviews these and other syndromes related to cranial nerves IX through XII that might be seen by psychiatry. PMID:20532157

  17. 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.

  18. School Environment and Academic Achievement of Standard IX Students

    ERIC Educational Resources Information Center

    Lawrence, A. S. Arul; Vimala, A.

    2012-01-01

    The present study School Environment and Academic Achievement of standard IX students was probed to find the relationship between School Environment and Academic Achievement of standard IX students. Data for the study were collected using self-made School Environment Scale (SES). The investigator used stratified random sampling technique for…

  19. 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…

  20. Cleavage and activation of human factor IX by serine proteases

    SciTech Connect

    Enfield, D.L.; Thompson, A.R.

    1984-10-01

    Human factor IX circulates as a single-chain glycoprotein. Upon activation in vitro, it is cleaved into disulfide-linked light and heavy chains and an activation peptide. After reduction of activated /sup 125/I-factor IX, the heavy and light chains are readily identified by gel electrophoresis. A direct, immunoradiometric assay for factor IXa was developed to assess activation of factor IX for proteases that cleaved it. The assay utilized radiolabeled antithrombin III with heparin to identify the active site and antibodies to distinguish factor IX. After cleavage of factor IX by factor XIa, factor VIIa-tissue thromboplastin complex, or the factor X-activating enzyme from Russell's viper venom, antithrombin III bound readily to factor IXa. Cleavage of /sup 125/I-factor IX by trypsin, chymotrypsin, and granulocyte elastase in the presence of calcium yielded major polypeptide fragments of the sizes of the factor XIa-generated light and heavy chains. When the immunoradiometric assay was used to assess trypsin-cleaved factor IX, the product bound antithrombin III, but not maximally. After digesting with insolubilized trypsin, clotting activity confirmed activation. In evaluating activation of factor IX, physical evidence of activation cleavages does not necessarily correlate with generation of an active site.

  1. A Model Community College Grievance Procedure for Title IX.

    ERIC Educational Resources Information Center

    Noonan, Roberta L.

    Through a review of the literature, analysis of eleven Title IX grievance plans, and interviews with four compliance officers, twelve criteria essential to an effective grievance procedure for use by students were identified and incorporated into a model Title IX grievance procedure for Moraine Valley Community College (Illinois). The twelve…

  2. 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…

  3. 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…

  4. Sex Bias in Secondary Schools: The Impact of Title IX.

    ERIC Educational Resources Information Center

    Fishel, Andrew; Pottker, Janice

    Title IX of the Education Amendments of 1972 is the first comprehensive anti-sex discrimination law that covers students. Although most of the attention given to the law since its passage has focused on its impact on colleges, Title IX will have the greatest impact on the elementary and secondary levels of education. All school districts in the…

  5. 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).

  6. 77 FR 64401 - Order of Succession for HUD Region IX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... URBAN DEVELOPMENT Order of Succession for HUD Region IX AGENCY: Office of Field Policy and Management, HUD. ACTION: Notice of Order of Succession. SUMMARY: In this notice, the Assistant Deputy Secretary... Succession for the San Francisco Regional Office and its Field Offices (Region IX). This Order of...

  7. 2 CFR Appendix Ix to Part 200 - Hospital Cost Principles

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... guidance is proposed and implemented for hospitals, the existing principles located at 45 CFR Part 74... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Hospital Cost Principles IX Appendix IX to Part 200 Grants and Agreements Office of Management and Budget Guidance for Grants and...

  8. 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

  9. Labeled factor IX kinetics in patients with hemophilia-B

    SciTech Connect

    Smith, K.J.; Thompson, A.R.

    1981-09-01

    Labeled factor IX was infused five time into four patients with hemophilia-B. Ten-minute plasma recovery average 35% (SD +/- 2) and the mean T 1/2 beta-phase elimination was 23 hr (+/- 5). No alteration in the postinfusion 125I-factor-IX could be detected by radioautography of plasma samples run on polyacrylamide gels or on crossed-immunoelectrophoresis. Label was excreted into the urine as free 125I-iodide. Kinetics were similar when the labeled preparation was infused alone or with a commercial concentrate containing unlabeled factor IX. Infusion of factor IX in man is best described by a two-compartment open pharmacokinetic model where factor IX is distributed in a space larger than the plasma volume.

  10. Foot deformities in Renaissance paintings. A mystery of symbolism, artistic licence, illusion and true representation in five renowned Renaissance painters.

    PubMed

    Lazzeri, D; Castello, M F; Grassetti, L; Dashti, T; Zhang, Y X; Persichetti, P

    2015-01-01

    Although Renaissance artists were skilled in representing normal anatomy, a close look at some paintings reveals anatomical variations in the depiction of the feet of human figures. A systematic review has identified 25 paintings by five artists in which the presumptive medico-artistic diagnosis of congenital or acquired foot deformity seems to be varyingly present. The connection between these five painters and what factors have influenced artists' style in the depiction of such deformities is discussed. The possible iconography and medical-historical meaning of such variations, as well as the possibility of artistic licence and real representation that drove the painters to depict these deformities, is explored and debated.

  11. The platelet glycoprotein Ib-IX complex.

    PubMed

    López, J A

    1994-02-01

    The GP Ib-IX complex is part of a conglomerate of polypeptides on the platelet surface that perform several key roles of central importance to the haemostatic function of platelets. When deranged, these interactions can also lead to pathological thrombosis, with potentially disastrous consequences for the organism. In this manuscript, several aspects of the structure and biology of the complex are reviewed, including the structures of its polypeptides and their relationships to other members of a phylogenetically widespread protein family, its topology on the platelet membrane and relationship with cytoskeletal components, peptide sequences involved in binding its ligands, von Willebrand factor and thrombin, its polymorphisms, its biosynthesis, and the organizations of the genes that encode its subunits.

  12. 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.

  13. 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.

  14. 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.

  15. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells

    SciTech Connect

    Vordermark, Dirk . E-mail: vordermark_d@klinik.uni-wuerzburg.de; Kaffer, Anja; Riedl, Susanne; Katzer, Astrid; Flentje, Michael

    2005-03-15

    Purpose: Published clinical studies provide conflicting data regarding the prognostic significance of carbonic anhydrase IX (CA IX) overexpression as an endogenous marker of tumor hypoxia and its comparability with other methods of hypoxia detection. We performed a systematic analysis of CA IX protein levels under various in vitro conditions of tumor hypoxia in HT 1080 human fibrosarcoma and FaDu human pharyngeal carcinoma cells. Because sorting of live CA IX positive cells from tumors provides a tool to study the radiosensitivity of chronically hypoxic cells, we modified and tested a CA IX flow cytometry protocol on mixed hypoxic/aerobic suspensions of HT 1080 and FaDu cells. Methods and materials: HT 1080 and FaDu cells were treated with up to 24 h of in vitro hypoxia and up to 96 h of reoxygenation. To test the effect of nonhypoxic stimuli, glucose and serum availability, pH and cell density were modified. CA IX protein was quantified in Western blots of whole-cell lysates. Mixed suspensions with known percentages of hypoxic cells were prepared for CA IX flow cytometry. The same mixtures were assayed for clonogenic survival after 10 Gy. Results: Hypoxia-induced CA IX protein expression was seen after >6 h at {<=}5% O{sub 2}, and protein was stable over 96 h of reoxygenation in both cell lines. Glucose deprivation abolished the hypoxic CA IX response, and high cell density caused CA IX induction under aerobic conditions. Measured percentages of CA IX-positive cells in mixtures closely reflected known percentages of hypoxic cells in HT 1080 and were associated with radioresistance of mixtures after 10 Gy. Conclusion: CA IX is a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. Except the time course of accumulation, all properties of this marker resembled our previous findings for hypoxia-inducible factor-1{alpha}. A modified flow cytometry protocol provided good separability of CA IX-negative and -positive cells in vitro

  16. 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.

  17. 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

  18. 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

  19. Anisotropic Bianchi types VIII and IX locally rotationally symmetric cosmologies

    SciTech Connect

    Assad, M.J.D.; Soares, I.D.

    1983-10-15

    We present a class of exact cosmological solutions of Einstein-Maxwell equations, which are anisotropic and spatially homogeneous of Bianchi types VIII and IX, and class IIIb in the Stewart-Ellis classification of locally rotationally symmetric models. If we take the electromagnetic field equal to zero, a class of Bianchi types VIII/IX spatially homogeneous anisotropic cosmological solutions with perfect fluid is obtained.

  20. Expression of active human factor IX in transfected cells.

    PubMed

    Busby, S; Kumar, A; Joseph, M; Halfpap, L; Insley, M; Berkner, K; Kurachi, K; Woodbury, R

    Factor IX is the precursor of a serine protease that functions in the intrinsic blood clotting pathway. Deficiencies in this plasma glycoprotein result in haemophilia B (or Christmas disease) and occur in about 1 in 30,000 males. Patients are currently treated with fresh frozen plasma or prothrombin complex concentrates prepared from pooled plasma from normal individuals. There are several problems with this method of treatment, including the probable exposure of the patients to contaminants such as the viral agents responsible for hepatitis and AIDS (acquired immune deficiency syndrome). As a first step towards an alternative source of pure human factor IX, we report here on the use of recombinant DNA techniques to produce biologically active factor IX in cultured mammalian cells. Stable cell lines were produced by cotransfecting a baby hamster kidney (BHK) cell line with a plasmid containing a gene for factor IX and a plasmid containing a selectable marker. Protein secreted by these cell lines reduces the clotting time of plasma from factor IX-deficient patients. We present additional evidence that this protein is authentic human factor IX.

  1. beta-meso-Phenylbiliverdin IX alpha and N-phenylprotoporphyrin IX, products of the reaction of phenylhydrazine with oxyhemoproteins.

    PubMed Central

    Saito, S; Itano, H A

    1981-01-01

    Oxyhemoglobin and oxymyoglobin were allowed to react aerobically with phenylhydrazine and p-tolylhydrazine. The chloroform extract of each reaction mixture, after treatment with H2SO4/methanol, yielded a blue pigment and a green pigment, which were identified by electronic absorption, mass, and proton NMR spectroscopy as the dimethyl esters of beta-meso-arylbiliverdin IX alpha and N-arylprotoporphyrin IX, respectively. N-Phenylprotoporphyrin IX dimethyl ester formed complexes with Zn2+, Cd2+, and Hg2+ but not with other cations. The proton NMR spectrum of the zinc complex suggested binding of the phenyl group to one of the two pyrrole rings of protoporphyrin IX with a propionic acid substituent. The effectiveness of phenylhydrazine as an inducer of Heinz body formation may be due to destabilization of the hemoglobin molecule by the replacement of heme with phenyl adducts of biliverdin and protoporphyrin. PMID:6946488

  2. Necessity of Periodic Ophthalmological Examinations in Binocular B Class Driving Licence Holders Over 50 Years of Age

    PubMed Central

    Kurt, Ali; Öktem, Çağlar; Karabıçak Acer, Ayşe; Kocamış, Özkan; Taşdemir, Sedat

    2016-01-01

    Objective: To determine whether binocular B class driving licence (BBCDL) holders over 50 years old are in compliance with the BBCDL criteria for visual acuity, to determine the age-based prevalence of ophthalmological disorders reducing visual acuity in this group, and to investigate whether periodic ophthalmological examinations are needed in licence holders over 50 years of age. Materials and Methods: This prospective study enrolled 451 adults over 50 years old having a BBCDL. The study subjects were categorized into 3 age groups as group 1 (51-60 years), group 2 (61-70 years), and group 3 (over 71 years). Results: The mean age of the subjects was 60.02±7.27 years; 338 (74.9%) were male and 113 (25.1%) were female. The BBCDL criteria were met by 353 (78.3%) subjects whereas 98 (21.7%) subjects did not meet them. Eighty-four (85.7%) of 98 patients not meeting BBCDL criteria still drove. The mean age of the subjects meeting BBCDL criteria (58.82±6.77 years) was significantly lower than the subjects not meeting them (64.34±7.40 years) (p<0.001). The most common pathologies in the individuals still driving despite not meeting BBCDL criteria were senile cataract (38.5%) and diabetic retinopathy (23.1%) in group 1, senile cataract (55.3%) and diabetic retinopathy (14.9%) in group 2, and senile cataract (63.6%) and senile macular degeneration+senile cataract (18.2%) in group 3. Conclusion: More than a fifth of individuals over 50 years old did not meet the BBCDL criteria, due predominantly to senile cataract, and the majority of these individuals continue to drive. Therefore, we believe that individuals over 50 years old who have a BBCDL should undergo periodic ophthalmological examinations.

  3. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX) during Hypoxia.

    PubMed

    Otsuka, Shimpei; Matsumoto, Kentaro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-Ichiro

    2015-01-01

    5-Aminolevulinic acid (ALA), a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX) in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII), an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis. PMID:26717566

  4. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX) during Hypoxia

    PubMed Central

    Otsuka, Shimpei; Matsumoto, Kentaro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    5-Aminolevulinic acid (ALA), a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX) in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII), an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis. PMID:26717566

  5. Neutrophil elastase cleavage of human factor IX generates an activated factor IX-like product devoid of coagulant function.

    PubMed

    Samis, J A; Kam, E; Nesheim, M E; Giles, A R

    1998-08-15

    In preliminary studies, the generation of thrombin in vivo was found to induce a 92% loss of functional activity of factor IX (F.IX) despite the detection by Western blotting of a product resembling activated F.IX (F.IXa) and a 25% increase in F.IX antigen levels (Hoogendoorn et al, Thromb Haemost 69:1127, 1993 [abstr]). These changes were associated with evidence of increased elastase availability. To study the possibility that these two observations were related, a detailed physical and functional characterization of the hydrolysis of purified human F.IX by human neutrophil elastase (HNE) was performed in vitro. An activated partial thromboplastin time (aPTT) clotting assay demonstrated that, although HNE eliminated the potential of F.IX to be activated, it only marginally reduced the F.IXa activity. Reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that HNE treatment of F.IX generated cleavage products of 30 and 20 kD that could not be distinguished from the respective heavy and light chain peptides that were identified in parallel studies when F.IX was activated by activated bovine F.XI (F.XIa), one of its physiological activators. In addition, nonreducing SDS-PAGE demonstrated that HNE-treated F.IX formed no complexes with antithrombin III (ATIII) in the presence of heparin. Furthermore, HNE-treated F.IX was unable to (1) bind the active site probe p-aminobenzamidine; (2) hydrolyze the synthetic peptide substrate CH3SO2-Leu-Gly-Arg-p-nitroanilide; and (3) activate human factor X (F.X). In contrast to dansyl-Glu-Gly-Arg-chloromethyl ketone (dEGR)-inactivated F.IXa, HNE-treated F.IX (0.01 to 10,000 pmol/L) failed to inhibit the clotting activity of F.IXa (10 pmol/L) in the aPTT. NH2-terminal sequencing indicated that HNE cleaved human F.IX at Thr140, Thr144, Ile164, Thr172, and Val181. The cleavages at Thr140/Thr144 and at Thr172/Val181 are both very close to the normal F.XIa alpha-(Arg145) and beta-(Arg180) cleavage sites

  6. Verdohemochrome IX alpha: preparation and oxidoreductive cleavage to biliverdin IX alpha.

    PubMed Central

    Saito, S; Itano, H A

    1982-01-01

    Several studies have shown that both terminal oxygen atoms of biliverdin are derived from molecular oxygen. Since the conversion of verdohemochrome to biliverdin has been assumed to be hydrolytic, these findings seemed to exclude verdohemochrome as an intermediate in the degradation of heme to biliverdin. Coupled oxidation of myoglobin and ascorbate yielded a pure preparation of verdohemochrome IX alpha. The structure and ferrous state of this product were determined from its composition, ligand reactions, 1H NMR spectrum, and conversion to biliverdin IX alpha dimethyl ester. Reaction with ascorbate and 18O2 converted this compound to biliverdin that contained an atom of 18O. Successive treatment of verdohemochrome, first oxidation with H2O2 and then reduction with phenylhydrazine, yielded the iron complex of biliverdin. These results showed that hydrolysis is not an obligatory step in the conversion of verdohemochrome to biliverdin and, moreover, indicated how heme can be converted, with verdohemochrome as an intermediate, into biliverdin in which the two terminal oxygen atoms are derived from different O2 molecules. PMID:6951184

  7. Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children

    PubMed Central

    Chambost, Hervé; Male, Christoph; Lambert, Thierry; Halimeh, Susan; Chernova, Tatiana; Mancuso, Maria Elisa; Curtin, Julie; Voigt, Christine; Li, Yanyan; Jacobs, Iris; Santagostino, Elena

    2016-01-01

    Summary A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531) PMID:27583313

  8. 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.

  9. Carbonic anhydrase IX: regulation and role in cancer.

    PubMed

    Benej, Martin; Pastorekova, Silvia; Pastorek, Jaromir

    2014-01-01

    Tumor microenvironment substantially influences the process of tumorigenesis. In many solid tumors, imbalance between the demand of rapidly proliferating cancer cells and the capabilities of the vascular system generates areas with insufficient oxygen supply. In response to tumor hypoxia, cancer cells modulate their gene expression pattern to match the requirements of the altered microenvironment. One of the most significant adaptations to this milieu is the shift towards anaerobic glycolysis to keep up the energy demands. This oncogenic metabolism is often maintained also in aerobic cells. Lactic acid, its metabolic end-product, accumulates hand-in-hand with carbon dioxide, leading to acidification of the extracellular environment. Carbonic anhydrase IX (CA IX) is the most widely expressed gene in response to hypoxia. Its crucial role in intracellular pH maintenance represents the means by which cancer cells adapt to the toxic conditions of the extracellular milieu. Furthermore, the activity of CA IX stimulates the migratory pathways of cancer cells and is connected with the increase of the aggressive/invasive phenotype of tumors. CA IX expression in many types of tumors indicates its relevance as a general marker of tumor hypoxia. Moreover, its expression is closely related to prognosis of the clinical outcome in several tumor types. All above mentioned facts support the strong position of CA IX as a potential drug therapy target. Here, we summarize the state-of-the-art knowledge on its regulation and role in cancer development.

  10. 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.

  11. Star Formation Rate in Holmberg IX Dwarf Galaxy

    NASA Astrophysics Data System (ADS)

    Andjelic, M. M.

    2011-12-01

    In this paper we use previously determined Hα fluxes for dwarf galaxy Holmberg IX (Arbutina et al. 2009) to calculate star formation rate (SFR) in this galaxy. We discuss possible contaminations of Hα flux and, for the first time, we take into account optical emission from supernova remnants (SNRs) as a possible source of contamination of Hα flux. Derived SFR for Holmberg IX is 3.4×10-4M_{⊙} yr-1. Our value is lower then in previous studies, due to luminous shock-heated source M&H 9-10, possible hypernova remnant, which we excluded from the total Hα flux in our calculation of SFR.

  12. 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.

  13. Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.

    PubMed Central

    Liebman, H A; Limentani, S A; Furie, B C; Furie, B

    1985-01-01

    Factor IX is a vitamin K-dependent blood clotting zymogen that is functionally defective or absent in patients with hemophilia B. A method of immunoaffinity chromatography has been developed for a one-step high yield purification of factor IX directly from plasma. The technique utilizes conformation-specific antibodies that bind solely to the metal-stabilized factor IX conformer, but not to the conformer of factor IX found in the absence of metal ions. Anti-factor IX-Ca(II) antibodies were immobilized on an agarose matrix. Human plasma in the presence of 7.5 mM MgCl2 was applied to the antibody-agarose column. The factor IX that binds to these antibodies was specifically eluted by metal chelation with EDTA. This immunopurification resulted in a 10,000-fold one-step purification of the fully functional zymogen. Purified factor IX yielded a single band upon gel electrophoresis in Na-DodSO4 and had a specific activity of 120-150 units/mg. The purified factor IX was separated from other vitamin K-dependent blood clotting proteins and hepatitis virus; no activated factor IX was detected. This method has application for the large scale purification of factor IX for the treatment of hemophilia B. Images PMID:2408269

  14. Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.

    PubMed

    Liebman, H A; Limentani, S A; Furie, B C; Furie, B

    1985-06-01

    Factor IX is a vitamin K-dependent blood clotting zymogen that is functionally defective or absent in patients with hemophilia B. A method of immunoaffinity chromatography has been developed for a one-step high yield purification of factor IX directly from plasma. The technique utilizes conformation-specific antibodies that bind solely to the metal-stabilized factor IX conformer, but not to the conformer of factor IX found in the absence of metal ions. Anti-factor IX-Ca(II) antibodies were immobilized on an agarose matrix. Human plasma in the presence of 7.5 mM MgCl2 was applied to the antibody-agarose column. The factor IX that binds to these antibodies was specifically eluted by metal chelation with EDTA. This immunopurification resulted in a 10,000-fold one-step purification of the fully functional zymogen. Purified factor IX yielded a single band upon gel electrophoresis in Na-DodSO4 and had a specific activity of 120-150 units/mg. The purified factor IX was separated from other vitamin K-dependent blood clotting proteins and hepatitis virus; no activated factor IX was detected. This method has application for the large scale purification of factor IX for the treatment of hemophilia B.

  15. 40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Ground-Water Monitoring List IX... Pt. 264, App. IX Appendix IX to Part 264—Ground-Water Monitoring List Ground-Water Monitoring List... species in the ground water that contain this element are included. 3 CAS index names are those used...

  16. 40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Ground-Water Monitoring List IX... Pt. 264, App. IX Appendix IX to Part 264—Ground-Water Monitoring List Ground-Water Monitoring List... species in the ground water that contain this element are included. 3 CAS index names are those used...

  17. 40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Ground-Water Monitoring List IX... Pt. 264, App. IX Appendix IX to Part 264—Ground-Water Monitoring List Ground-Water Monitoring List... species in the ground water that contain this element are included. 3 CAS index names are those used...

  18. 40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Ground-Water Monitoring List IX... Pt. 264, App. IX Appendix IX to Part 264—Ground-Water Monitoring List Ground-Water Monitoring List... species in the ground water that contain this element are included. 3 CAS index names are those used...

  19. 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.

  20. 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.

  1. 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…

  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. 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.

  4. 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.

  5. Working in tandem: The contribution of remedial programs and roadside licence suspensions to drinking and driving deterrence in Ontario.

    PubMed

    Ma, Tracey; Byrne, Patrick A; Haya, Maryam; Elzohairy, Yoassry

    2015-12-01

    In 1998, Ontario implemented a remedial program called "Back On Track" (BOT) for individuals convicted of alcohol-impaired driving. Drivers convicted before October 2000 were exposed to a single-component program ("Edu BOT"); those convicted after participated in a multi-component program ("Full BOT"). We evaluated the impact of BOT, and the preceding 90-day roadside licence suspension, on drinking and driving recidivism, an outcome yet to be examined, using population-wide driver records. A Chi Square Test was used to compare the three-year cumulative incidence of recidivism between three historically-defined cohorts: No BOT, Edu BOT, and Full BOT. Stratified analyses by completion status and by age were also conducted. Analyses of the roadside suspension were conducted using an interrupted time series approach based on segmented Poisson/negative binomial regression. The roadside suspension was associated with a 65.2% reduction in drinking driving recidivism. In combination with indefinite suspensions for non-completion, the BOT program was also associated with a 21% decrease in drinking and driving recidivism in the three years following a CCC driving prohibition, from 8.5% to 6.7%. This reduction cannot be explained by pre-existing trends in recidivism. Conversion of the BOT program from the single-component version to the multi-component program further reduced the three-year cumulative incidence of recidivism to 5.5% (a total reduction of 35% from pre-BOT). Results provide strong converging evidence that remedial alcohol education/treatment programs in combination with other sanctions can produce substantial increases in road safety.

  6. Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody.

    PubMed

    Goodall, A H; Kemble, G; O'Brien, D P; Rawlings, E; Rotblat, F; Russell, G C; Janossy, G; Tuddenham, E G

    1982-03-01

    A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.

  7. 40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B) IX Appendix IX to Part 268 Protection of.... 268, App. IX Appendix IX to Part 268—Extraction Procedure (EP) Toxicity Test Method and...

  8. 40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B) IX Appendix IX to Part 268 Protection of.... 268, App. IX Appendix IX to Part 268—Extraction Procedure (EP) Toxicity Test Method and...

  9. 40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B) IX Appendix IX to Part 268 Protection of.... 268, App. IX Appendix IX to Part 268—Extraction Procedure (EP) Toxicity Test Method and...

  10. 40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B) IX Appendix IX to Part 268 Protection of.... 268, App. IX Appendix IX to Part 268—Extraction Procedure (EP) Toxicity Test Method and...

  11. 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

  12. Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death.

    PubMed

    Wang, Yan; Cordewener, Jan H G; America, Antoine H P; Shan, Weixing; Bouwmeester, Klaas; Govers, Francine

    2015-09-01

    L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

  13. In-vivo fluorescence dosimetry of aminolevulinate-based protoporphyrin IX (PpIX) accumulation in human nonmelanoma skin cancers and precancers

    NASA Astrophysics Data System (ADS)

    Warren, Christine B.; Lohser, Sara; Chang, Sung; Bailin, Philip A.; Maytin, Edward V.

    2009-06-01

    PDT is clinically useful for precancers (actinic keratoses; AK) of the skin, but the optimal duration for 5-ALA application is still controversial. For basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), cure rates remain inferior to surgical excision. Lack of knowledge about regional levels of PpIX levels within target tissues clearly contribute to these suboptimal results. To investigate PpIX levels achievable in human skin neoplasias in-vivo, a clinical study to monitor PpIX accumulation in vivo was performed. PpIX-fluorescence in patients undergoing ALA-PDT for facial AK was monitored via real-time in-vivo fluorescence dosimetry, with measurements q20 min following application of 5-ALA (Levulan Kerastick). PpIX accumulation followed linear kinetics in nearly all cases. The slopes varied widely, and did not correlate with clinical outcome in all patients. Some patients with a low accumulation of PpIX fluorescence had a good response to therapy, whereas others with high PpIX accumulation required repeat treatment (although not necessarily of the same lesion). PpIX accumulation rates did correlate to a certain degree with the overall amount of erythema. We conclude that unknown factors besides PpIX levels must be critical for the response to treatment. To assess the relationship between PpIX levels in various skin cancers, patients undergoing routine Mohs surgery for BCC or SCC were measured by in-vivo dosimetry at 2 h after 5-ALA application. Overall, a progressive increase in PpIX signal during malignant progression was observed, in the following rank order: Normal skin < AK < SCC ~ BCC.

  14. 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

  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. 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.

  17. The gene structure of human anti-haemophilic factor IX.

    PubMed

    Anson, D S; Choo, K H; Rees, D J; Giannelli, F; Gould, K; Huddleston, J A; Brownlee, G G

    1984-05-01

    The mRNA sequence of the human intrinsic clotting factor IX (Christmas factor) has been completed and is 2802 residues long, including a 29 residue long 5' non-coding and a 1390 residue long 3' non-coding region, but excluding the poly(A) tail. The factor IX gene is approximately 34 kb long and we define, by the sequencing of 5280 residues, the presumed promoter region, all eight exons, and some intron and flanking sequence. Introns account for 92% of the gene length and the longest is estimated to be 10 100 residues. Exons conform roughly to previously designated protein regions, but the catalytic region of the protein is coded by two separate exons. This differs from the arrangement in the other characterized serine protease genes which are further subdivided in this region.

  18. Technical Progress on the Ares I-X Flight Test

    NASA Technical Reports Server (NTRS)

    Davis, S.R.; Robinson, K.F.; Flynn, K.C.

    2008-01-01

    Ares I-X will be NASA's first test flight for a new human-rated launch vehicle since 1981, and the team is well on its way toward completing the vehicle's design and hardware fabrication for an April 2009 launch. This uncrewed suborbital development test flight gives NASA its first opportunities to: gather critical data about the flight dynamics of the integrated launch vehicle; understand how to control its roll during flight; better characterize the stage separation environments during future flight; and demonstrate the first stage recovery system. The Ares I-X Flight Test Vehicle (FTV) incorporates a mix of flight and mockup hardware. It is powered by a four-segment solid rocket booster, and will be modified to include a fifth, spacer segment; the upper stage, Orion crew exploration vehicle, and launch abort system are simulator hardware to make the FTV aerodynamically similar to the same size, shape, and weight of Ares I. The Ares IX first stage includes an existing Shuttle solid rocket motor and thrust vector control system controlled by an Ascent Thrust Vector Controller (ATVC) designed and built by Honeywell International. The avionics system will be tested in a dedicated System Integration Laboratory located at Lockheed Martin Space Systems (LMSS) in Denver, Colorado. The Upper Stage Simulator (USS) is made up of cylindrical segments that will be stacked and integrated at Kennedy Space Center (KSC) for launch. Glenn Research Center is already building these segments, along with their internal access structures. The active Roll Control System (RoCS) includes two thruster units harvested from Peacekeeper missiles. Duty cycle testing for RoCS was conducted, and fuel tanking and detanking tests will occur at KSC in early 2008. This important flight will provide valuable experience for the ground operations team in integrating, stacking, and launching Ares I. Data from Ares I-X will ensure the safety and reliability of America's newest launch vehicle.

  19. Loop quantum cosmology of Bianchi type IX models

    SciTech Connect

    Wilson-Ewing, Edward

    2010-08-15

    The loop quantum cosmology 'improved dynamics' of the Bianchi type IX model are studied. The action of the Hamiltonian constraint operator is obtained via techniques developed for the Bianchi type I and type II models, no new input is required. It is shown that the big bang and big crunch singularities are resolved by quantum gravity effects. We also present effective equations which provide quantum geometry corrections to the classical equations of motion.

  20. 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.

  1. Active gamma-carboxylated human factor IX expressed using recombinant DNA techniques.

    PubMed

    de la Salle, H; Altenburger, W; Elkaim, R; Dott, K; Dieterlé, A; Drillien, R; Cazenave, J P; Tolstoshev, P; Lecocq, J P

    Factor IX (Christmas factor), a vitamin K-dependent plasma protein made in the liver, functions in the middle phase of the intrinsic pathway of blood coagulation. A functional deficiency of factor IX underlies haemophilia B, a chromosome X-linked recessive disease for which the major therapeutic approach is replacement treatment using factor IX concentrates. The cloning and characterization of the gene for human factor IX would mean that human factor IX could be produced in greater yield and purity through using recombinant DNA techniques. We have now used a human factor IX cDNA clone, inserted into a vaccinia virus-derived vector, to infect human hepatoma cells which normally produce no factor IX, and mouse fibroblasts. Fully active factor IX was produced by the hepatoma cells, whereas the fibroblasts produced a protein less active than natural factor IX, even in the presence of high levels of vitamin K. Human factor IX is extensively post-translationally modified, and thus represents probably the most complex protein produced in active form by recombinant DNA techniques to date. Our study also illustrates the potential of vaccinia virus-based vectors for expressing significant amounts of complex, clinically useful proteins in eukaryotic cells, in addition to its already demonstrated usefulness for producing live recombinant vaccines.

  2. Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients

    PubMed Central

    Kalavska, Katarina; Chovanec, Michal; Zatovicova, Miriam; Takacova, Martina; Gronesova, Paulina; Svetlovska, Daniela; Baratova, Magdalena; Miskovska, Vera; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Sycova-Mila, Zuzana; Cierna, Zuzana; Kajo, Karol; Spanik, Stanislav; Babal, Pavel; Mardiak, Jozef; Pastorekova, Silvia; Mego, Michal

    2016-01-01

    Despite the fact that testicular germ cell tumors (TGCTs) are one of the most chemosensitive solid tumors, a small proportion of patients fail to be cured following cisplatin-based first line chemotherapy. Upregulation of carbonic anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The current prospective study investigated the prognostic value of serum CA IX level in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no evidence of disease, 57 metastatic chemotherapy-naïve and 10 metastatic relapsed chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35 healthy controls were enrolled in the study. Serum CA IX values were determined using an enzyme-linked immunosorbent assay, and intratumoral CA IX was analyzed by immunohistochemistry. Metastatic chemotherapy-naïve patients had significantly higher mean CA IX serum levels than healthy controls (490.6 vs. 249.6 pg/ml, P=0.005), while there was no difference in serum CA IX levels in non-metastatic or relapsed TGCT patients compared with healthy controls. There was no significant difference in the mean serum CA IX levels between different groups of patients and between the first and second cycle of chemotherapy, nor association with patients/tumor characteristics. Serum CA IX was not prognostic for progression-free survival [hazard ratio (HR)=0.81, P=0.730] or overall survival (HR=0.64, P=0.480). However, there was a significant association between intratumoral CA IX expression and serum CA IX concentration (rho=0.51, P=0.040). These results suggest that serum CA IX level correlates with tumor CA IX expression in TGCT patients, but fails to exhibit either a prognostic value or an association with patients/tumor characteristics. PMID:27698832

  3. Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients

    PubMed Central

    Kalavska, Katarina; Chovanec, Michal; Zatovicova, Miriam; Takacova, Martina; Gronesova, Paulina; Svetlovska, Daniela; Baratova, Magdalena; Miskovska, Vera; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Sycova-Mila, Zuzana; Cierna, Zuzana; Kajo, Karol; Spanik, Stanislav; Babal, Pavel; Mardiak, Jozef; Pastorekova, Silvia; Mego, Michal

    2016-01-01

    Despite the fact that testicular germ cell tumors (TGCTs) are one of the most chemosensitive solid tumors, a small proportion of patients fail to be cured following cisplatin-based first line chemotherapy. Upregulation of carbonic anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The current prospective study investigated the prognostic value of serum CA IX level in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no evidence of disease, 57 metastatic chemotherapy-naïve and 10 metastatic relapsed chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35 healthy controls were enrolled in the study. Serum CA IX values were determined using an enzyme-linked immunosorbent assay, and intratumoral CA IX was analyzed by immunohistochemistry. Metastatic chemotherapy-naïve patients had significantly higher mean CA IX serum levels than healthy controls (490.6 vs. 249.6 pg/ml, P=0.005), while there was no difference in serum CA IX levels in non-metastatic or relapsed TGCT patients compared with healthy controls. There was no significant difference in the mean serum CA IX levels between different groups of patients and between the first and second cycle of chemotherapy, nor association with patients/tumor characteristics. Serum CA IX was not prognostic for progression-free survival [hazard ratio (HR)=0.81, P=0.730] or overall survival (HR=0.64, P=0.480). However, there was a significant association between intratumoral CA IX expression and serum CA IX concentration (rho=0.51, P=0.040). These results suggest that serum CA IX level correlates with tumor CA IX expression in TGCT patients, but fails to exhibit either a prognostic value or an association with patients/tumor characteristics.

  4. New polymorphic variants of human blood clotting factor IX

    SciTech Connect

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V.; Plutalov, O.V.; Berlin, Yu.A.

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  5. Evidence that biliverdin-IX beta reductase and flavin reductase are identical.

    PubMed Central

    Shalloe, F; Elliott, G; Ennis, O; Mantle, T J

    1996-01-01

    A search of the database shows that human biliverdin-IX beta reductase and flavin reductase are identical. We have isolated flavin reductase from bovine erythrocytes and show that the activity co-elutes with biliverdin-IX beta reductase. Preparations of the enzyme that are electrophoretically homogeneous exhibit both flavin reductase and biliverdin-IX beta reductase activities; however, they are not capable of catalysing the reduction of biliverdin-IX alpha. Although there is little obvious sequence identity between biliverdin-IX alpha reductase (BVR-A) and biliverdin-IX beta reductase (BVR-B), they do show weak immunological cross-reactivity. Both enzymes bind to 2',5'-ADP-Sepharose. PMID:8687377

  6. Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.

    PubMed

    Anson, D S; Austen, D E; Brownlee, G G

    Haemophilia B, or Christmas disease, is an inherited X-chromosome-linked bleeding disorder caused by a defect in clotting factor IX and occurs in about 1 in 30,000 males in the United Kingdom. Injection of factor IX concentrate obtained from blood donors allows most patients to be successfully managed. However, because of impurities in the factor IX concentrate presently in use, this treatment involves some risk of infection by blood-borne viruses such as non-A, non-B hepatitis and the virus causing acquired immune deficiency syndrome (AIDS). Because of the recent concern about the increasing incidence of AIDS amongst haemophiliacs, a factor IX preparation derived from a source other than blood is desirable. Here, we report that after introduction of human factor IX DNA clones into a rat hepatoma cell line using recombinant DNA methods, we were able to isolate small amounts of biologically active human factor IX.

  7. Determination of aminolevulinic-acid-induced protoporphyrin IX in mice skin

    NASA Astrophysics Data System (ADS)

    Stolik, S.; Tomás, S. A.; Ramón-Gallegos, E.; Cruz-Orea, A.; Sánchez-Sinencio, F.

    2003-01-01

    The kinetics of Protoporphyrin IX (PpIX) production in mice skin was studied by photoacoustic spectroscopy. PpIX was induced in mice by intraperitoneal administration of δ-aminolevulinic acid (δ-ALA) in doses of 10, 20, and 30 mg/kg. Mice were sacrificed at specific times within an 8 h interval following δ-ALA administration, and their abdominal skin was excised for the optical measurements. The PpIX content was determined from the photoacoustic amplitude at 410 nm, where PpIX presents its Soret band. For each dose, maximum PpIX was observed at two points. The first maximum occurred at around 15-45 min, depending on the ALA dose, and the second one took place approximately 2 h after δ-ALA administration. These peaks are associated with PpIX production in blood vessels and tissue, respectively. Fluorescence measurements of the PpIX content in plasma extracted intracardiacally confirmed the previous statement. Finally, phase resolved photoacoustic spectroscopy was applied to evaluate the mean depth at which PpIX is generated within the mice skin. This evaluation confirms that the ALA-induced porphyrins in skin are rather produced in the epidermis than in the dermis.

  8. 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. PMID:27439028

  9. Cell cycle dependence of protophorphyrin IX generation in 9L rat gliosarcoma

    NASA Astrophysics Data System (ADS)

    Luo, Shiming; Da, Xing; Chen, Qun

    2006-09-01

    Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target tissue. Always, the curative effect is dependent on the light fluence, the concentration of the photosensitizer and the concentration of the oxygen. To date, Protophorphyrin IX (PpIX) as the only one endogenous photosensitizer is widely used in PDT of brain tumors. Since PpIX is synthesized in intracellular structure, and is likely dependent on the phase of the cell cycle. The cell cycle dependence of PpIX production is thus investigated in the current work in 9L gliosarcoma cells.

  10. 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.

  11. Saccharin: a lead compound for structure-based drug design of carbonic anhydrase IX inhibitors.

    PubMed

    Mahon, Brian P; Hendon, Alex M; Driscoll, Jenna M; Rankin, Gregory M; Poulsen, Sally-Ann; Supuran, Claudiu T; McKenna, Robert

    2015-02-15

    Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and a prognostic marker and target for several cancers. Saccharin (SAC) based compounds may provide an avenue to overcome CA isoform specificity, as they display both nanomolar affinity and preferential binding, for CA IX compared to CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate bound to a CA IX-mimic are presented and compared to CA II. The structures provide substantial new insight into the mechanism of SAC selective CA isoform inhibition.

  12. Mg-Protoporphyrin IX Signals Enhance Plant’s Tolerance to Cold Stress

    PubMed Central

    Zhang, Zhong-Wei; Wu, Zi-Li; Feng, Ling-Yang; Dong, Li-Hua; Song, An-Jun; Yuan, Ming; Chen, Yang-Er; Zeng, Jian; Chen, Guang-Deng; Yuan, Shu

    2016-01-01

    The relationship between Mg-protoporphyrin IX (Mg-Proto IX) signals and plant’s tolerance to cold stress is investigated. Arabidopsis seedlings grown for 3 weeks were pretreated with 2 mM glutamate (Glu) and 2 mM MgCl2 for 48 h at room temperature to induce Mg-Proto IX accumulation. Then cold stress was performed at 4°C for additional 72 h. Glu + MgCl2 pre-treatments alleviated the subsequent cold stress significantly by rising the leaf temperature through inducing Mg-Proto IX signals. The protective role of Glu + MgCl2 treatment was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling, and cyanide-resistant respiration. And the enhancement of cold-responsive gene expression was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling and ABA signaling, but not in the mutant of cyanide-resistant respiration. Cold stress promoted cyanide-resistant respiration and leaf total respiration exponentially, which could be further induced by the Glu + MgCl2 treatment. Mg-Proto IX signals also activate antioxidant enzymes and increase non-enzymatic antioxidants [glutathione but not ascorbic acid (AsA)] to maintain redox equilibrium during the cold stress. PMID:27803706

  13. Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease.

    PubMed Central

    Fässler, R; Schnegelsberg, P N; Dausman, J; Shinya, T; Muragaki, Y; McCarthy, M T; Olsen, B R; Jaenisch, R

    1994-01-01

    Type IX collagen is a nonfibrillar collagen composed of three gene products, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules are localized on the surface of type II-containing fibrils and consist of two arms, a long arm that is crosslinked to type II collagen and a short arm that projects into the perifibrillar space. In hyaline cartilage, the alpha 1(IX) collagen transcript encodes a polypeptide with a large N-terminal globular domain (NC4), whereas in many other tissues an alternative transcript encodes an alpha 1(IX) chain with a truncated NC4 domain. It has been proposed that type IX molecules are involved in the interaction of fibrils with each other or with other components of the extracellular matrix. To test this hypothesis, we have generated a mouse strain lacking both isoforms of the alpha 1(IX) chain. Homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis. Images PMID:8197187

  14. Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases.

    PubMed Central

    Fevery, J; Van de Vijver, M; Michiels, R; Heirwegh, K P

    1977-01-01

    The bilrubin-IXalpha conjugates in bile and the activities of bilirubin-IX alpha--UDP-glycosyltransferases in liver and kidney were determined for ten species of mammals and for the chicken. 1. In the mammalian species, bilirubin-IX alpha glucuronide was the predominant bile pigment. Excretion of neutral glycosides was unimportant, except in the cat, the mouse, the rabbit and the dog, where glucose and xylose represented 12--41% of total conjugating groups bound to bilirubin-IX alpha. In chicken bile, glucoside and glucuronide conjugates were of equal importance. They probably represent only a small fraction of the total bile pigment. 2. The transferase activities in liver showed pronounced species variation. This was also apparent with regard to activation by digitonin, pH optimum and relative activities of transferases acting on either UDP-glucuronic acid or neutral UDP-sugars. 3. Man, the dog, the cat and the rat excrete bilirubin-IX alpha largely as diconjugated derivatives. In general, diconjugated bilirubin-IX alpha could also be synthesized in vitro with liver homogenate, bilirubin-IX alpha and UDP-sugar. In contrast, for the other species examined, bilirubin pigments consisted predominantly of monoconjugated bilirubin-IX alpha. Synthesis in vitro with UDP-glucuronic acid, UDP-glucose or UDP-xylose as the sugar donor led exclusively to the formation of monoconjugated bilirubin-IX alpha. 4. The transferase activities in the kidney were restricted to the cortex and were important only for the rat and the dog. No activity at all could be detected for several species, including man. 5. Comparison of the transferase activities in liver with reported values of the maximal rate of excretion in bile suggests a close linkage between conjugation and biliary secretion of bilirubin-IX alpha. PMID:407905

  15. The Transmembrane Domains of β and IX Subunits Mediate the Localization of the Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane Domain.

    PubMed

    Xu, Guofeng; Shang, Dan; Zhang, Zuping; Shaw, Tanner S; Ran, Yali; López, José A; Peng, Yuandong

    2015-09-01

    We have previously reported that the structural elements of the GP Ib-IX complex required for its localization to glycosphingolipid-enriched membranes (GEMs) reside in the Ibβ and IX subunits. To identify them, we generated a series of cell lines expressing mutant GP Ibβ and GP IX where 1) the cytoplasmic tails (CTs) of either or both GP Ibβ and IX are truncated, and 2) the transmembrane domains (TMDs) of GP Ibβ and GP IX were swapped with the TMD of a non-GEMs associating molecule, human transferrin receptor. Sucrose density fractionation analysis showed that the removal of either or both of the CTs from GP Ibβ and GP IX does not alter GP Ibα-GEMs association when compared with the wild type. In contrast, swapping of the TMDs of either GP Ibβ or GP IX with that of transferrin receptor results in a significant loss (∼ 50%) of GP Ibα from the low density GEMs fractions, with the largest effect seen in the dual TMD-replaced cells (> 80% loss) when compared with the wild type cells (100% of GP Ibα present in the GEMs fractions). Under high shear flow, the TMD-swapped cells adhere poorly to a von Willebrand factor-immobilized surface to a much lesser extent than the previously reported disulfide linkage dysfunctional GP Ibα-expressing cells. Thus, our data demonstrate that the bundle of GP Ibβ and GP IX TMDs instead of their individual CTs is the structural element that mediates the β/IX complex localization to the membrane GEMs, which through the α/β disulfide linkage brings GP Ibα into the GEMs. PMID:26203189

  16. 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.

  17. Extremity War Injuries IX: Reducing Disability Within the Military.

    PubMed

    Andersen, Col Romney C; Schmidt, Andrew H; Fitzgerald, Capt Brian T; Tintle, Lcdr Scott M; Helgeson, Maj Melvin D; Lehman, Ltc Ronald A; Davila, Col Jeffrey N; Potter, Benjamin K; Burns, Maj Travis C; Swiontkowski, Marc F; Ficke, Col James R

    2015-08-01

    Extremity War Injury Symposium IX focused on reducing disability within the military, centering on cartilage defects, amputations, and spinal cord injury. Many areas of upper and lower extremity trauma and disability were discussed, including segmental nerve injuries, upper extremity allotransplantation, and the importance of patient-reported functional outcomes compared with the traditionally reported measures. Strategic planning addressed progression toward clinical solutions by setting clear objectives and goals and outlining pathways to address the "translation gap" that often prevents bridging of basic science to clinical application.

  18. Spectral hole burning study of protoporphyrin IX substituted myoglobin.

    PubMed Central

    Zollfrank, J; Friedrich, J; Parak, F

    1992-01-01

    Protoporphyrin IX substituted myoglobin reveals excellent hole burning properties. We investigated the frequency shift of persistent spectral holes under isotropic pressure conditions in a range from 0 to 2.4 MPa. In this range, the protein behaves like an elastic solid. The shift of the holes under pressure shows a remarkable frequency dependence from which the compressibility of the protein can be determined. The compressibility, in turn, allows for an estimation of the equilibrium volume fluctuations. Within the frame of the model used to interpret the pressure data, it is possible to determine the absorption frequency of the isolated chromophore and the associated solvent shift in the protein environment. PMID:1504243

  19. Factor IX molecular defects in diagnosing hemophilia B: a review.

    PubMed

    Tanimoto, M

    1989-07-01

    The past several years have seen an explosive growth in the application of recombinant DNA methods to study the molecular pathology of various inherited disorders. As a consequence, molecular defects responsible for the disease have been identified at the sequence level. In this review, I briefly describe the recent progress in the uses of factor IX gene probes in clinical diagnosis of hemophilia B (Christmas disease) carriers, as well as their use for analyzing the structural gene abnormalities that are responsible for the disease.

  20. Optimization of a Novel Peptide Ligand Targeting Human Carbonic Anhydrase IX

    PubMed Central

    Rana, Shoaib; Nissen, Felix; Marr, Annabell; Markert, Annette; Altmann, Annette; Mier, Walter; Debus, Juergen; Haberkorn, Uwe; Askoxylakis, Vasileios

    2012-01-01

    Background Carbonic anhydrase IX (CA IX) is a hypoxia-regulated transmembrane protein over-expressed in various types of human cancer. Recently, a new peptide with affinity for human carbonic anhydrase IX (CaIX-P1) was identified using the phage display technology. Aim of the present study is to characterize the binding site in the sequence of CaIX-P1, in order to optimize the binding and metabolic properties and use it for targeting purposes. Methodology/Principal Findings Various fragments of CaIX-P1 were synthesized on solid support using Fmoc chemistry. Alanine scanning was performed for identification of the amino acids crucial for target binding. Derivatives with increased binding affinity were radiolabeled and in vitro studies were carried out on the CA IX positive human renal cell carcinoma cell line SKRC 52 and the CA IX negative human pancreatic carcinoma cell line BxPC3. Metabolic stability was investigated in cell culture medium and human serum. Organ distribution and planar scintigraphy studies were performed in Balb/c nu/nu mice carrying subcutaneously transplanted SKRC 52 tumors. The results of our studies clearly identified amino acids that are important for target binding. Among various fragments and derivatives the ligand CaIX-P1-4-10 (NHVPLSPy) was found to possess increased binding potential in SKRC 52 cells, whereas no binding capacity for BxPC3 cells was observed. Binding of radiolabeled CaIX-P1-4-10 on CA IX positive cells could be inhibited by both the unlabeled and the native CaIX-P1 peptide but not by control peptides. Stability experiments indicated the degradation site in the sequence of CaIX-P1-4-10. Biodistribution studies showed a higher in vivo accumulation in the tumor than in most healthy tissues. Conclusions Our data reveal modifications in the sequence of the CA IX affine ligand CaIX-P1 that might be favorable for improvement of target affinity and metabolic stability, which are necessary prior to the use of the ligand in

  1. 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.

  2. 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.

  3. Rules of the game change for comparing IX to RO

    SciTech Connect

    Stoebenau, H.P.

    1995-08-01

    This article examines how modern packed-bed demineralization with reverse-flow regeneration counters the notion that reverse osmosis is superior to ion exchange, the classical method for treating powerplant makeup water. Recently published articles argue that demineralization for industrial water treatment is steadily becoming the domain of membrane processes based on reverse osmosis (RO). For some experts, the economic crossover pint at which RO outperforms ion exchange (IX) for makeup-water demineralization occurs at a total dissolved solids (TDS) level of 75 ppm. However, three developments during the past five years have completely changed the basis for the IX-vs-RO debate, even at TDS levels as high as 400 to 500 ppm. These are: (1) An improved understanding of the operating characteristics of RO. (2) The application of jetted-resin technology for producing uniform-particle-size (UPS) resin. (3) Refinement of the packed-bed, reverse-flow (RF) demineralization technique, greatly reducing operating and capital costs.

  4. 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.

  5. The PhIX High Intensity Plasma Source

    NASA Astrophysics Data System (ADS)

    Goulding, R. H.; Caughman, J. B. O.; Peng, Y.-K. M.; Rapp, J.; Rasmussen, D. A.; Biewer, T. M.; Canik, J. M.; Chen, G.; Diem, S. J.; Meitner, S. J.; Owen, L. W.

    2012-10-01

    The Physics Integration eXperiment (PhIX) is a linear high-intensity rf plasma source presently being constructed at ORNL that combines a high density helicon plasma generator with an electron heating section. It will be used to explore the physics related to heating an overdense, streaming plasma in a linear geometry by whistler waves and Electron Bernstein Waves (EBW), including optimization of heating efficiency and maximization of particle flux. Interactions between the plasma production and heating regions, and the source and a downstream target, will also be investigated. Experiments using the device will provide data for the design of an rf powered high particle flux (˜10^24/m^2- s), high heat flux(˜10 MW /m^2) steady-state linear plasma-materials test station (PMTS). In preparatory experiments, the helicon device has operated at power levels up to 90 kW, producing high plasma densities in He (6 x10^19 m-3) and D (> 4 x10^19 m-3), and has also operated at high magnetic field strength up to 0.5 T. Separate ECH experiments have demonstrated both whistler and EBW coupling at 6 GHz to an overdense plasma. A review of these experiments will be presented, as well as an overview of PhIX and its status.

  6. 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…

  7. "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…

  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. Derivation of a triple mosaic adenovirus based on modification of the minor capsid protein IX

    SciTech Connect

    Tang Yizhe; Le, Long P.; Matthews, Qiana L.; Han Tie; Wu Hongju; Curiel, David T.

    2008-08-01

    Adenoviral capsid protein IX (pIX) has been shown to be a potential locale to insert targeting, imaging-related and therapeutic modalities by genetic modification. Recent evidences suggested that capsid protein mosaicism could be a promising strategy for improving the utility of Ad vector. In this study, we explored a method to genetically generate triple pIX mosaic Ad serotype 5 (Ad5) displaying three types of pIX on a single virion. pIXs were modified at their carboxy termini with a Flag sequence, a hexahistidine sequence (His{sub 6}) or a monomeric red fluorescent protein (mRFP1), respectively. Western blotting analysis and fluorescence microscopy of the purified recombinant viruses indicated that all three modified pIXs were incorporated into the viral particles. Immuno-gold electron microscopy (EM) further confirmed that three types of pIX indeed co-existed on an individual virion. These results firstly validated a triple mosaic capsid configuration on pIX, and demonstrated the possibility of further radical design.

  10. Summary of the Regulation for Title IX Education Amendments of 1972.

    ERIC Educational Resources Information Center

    Association of American Colleges, Washington, DC. Project on the Status and Education of Women.

    Title IX of the Education Amendemtns of 1972 bars sex discrimination in any academic, extracurricular, research, occupational training or other educational program operated by an organization or agency that receives or benefits from federal aid. The regulation (45 CFR Part 86) for Title IX summarized in this document falls into five categories:…

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

    ERIC Educational Resources Information Center

    Dunkle, Margaret C.; Sandler, Bernice

    1974-01-01

    Title IX of the Education Amendments of 1972 mandates that sex discrimination be eliminated in federally assisted education programs. Although a few issues such as competitive athletics have generated wide interest, Title IX has significant implications for a variety of less publicized issues including recruiting, admissions, financial aid,…

  12. Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Campbell, C. L.; Brown, C. T. A.; Wood, K.; Moseley, H.

    2016-11-01

    Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distribution.

  13. Title IX: What It Means and Doesn't Mean to Athletic Programs.

    ERIC Educational Resources Information Center

    Dunkle, Margaret C.

    This document examines equal opportunity for women in athletic programs--one of the most closely scrutinized and least understood issues of Title IX. Areas considered are: (1) basic provisions of Title IX; (2) the self-evaluation requirement; (3) grievance procedures; (4) the "adjustment period"; (5) overall equal athletic opportunity; (6) student…

  14. 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.

  15. 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.

  16. Improved in vitro and in vivo cutaneous delivery of protoporphyrin IX from PLGA-based nanoparticles.

    PubMed

    da Silva, Carolina L; Del Ciampo, José O; Rossetti, Fábia C; Bentley, Maria V L B; Pierre, Maria B R

    2013-01-01

    We report the development of D, L lactic co-glycolic acid) (PLGA)-based nanoparticles (NPs) for topical delivery of protoporphyrin IX (PpIX), a photosensitizer (PS), in treatments like photodynamic therapy (PDT) of skin cancers. PpIX-NPs were obtained in ~75.0% yield, encapsulation efficiency of 67.7%, drug content of 50.3 μg mg(-1), average diameter of 290 nm maintained up to 30 days and a zeta potential of 32.3 mV. Sustained in vitro release of PpIX through artificial membranes following Higuchi kinetics was kept up to 10 days. In vitro retentions of PpIX both in stratum corneum (SC) and epidermis + dermis ([EP + D]) were higher from NPs (23.0 and 10.0 times, respectively) compared to control solutions at all times. Quantification of PpIX by extraction, after in vivo skin application of NPs-PpIX on hairless mice, showed higher retention of the PS both in SC and in [EP + D] (3.0 and 2.0 times, respectively) compared to control solutions. Taken together, the results indicate that NPs are suitable for PpIX encapsulation showing minimal permeation through the skin and a localized effect, characteristics of a potential and promising delivery system for PDT-associated treatments of skin cancers, photodiagnosis and their off-label uses.

  17. 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…

  18. 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 opportunities for…

  19. 45 CFR 83.5 - Effect of title IX of the Education Amendments of 1972.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Effect of title IX of the Education Amendments of 1972. 83.5 Section 83.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972....

  20. 45 CFR 83.5 - Effect of title IX of the Education Amendments of 1972.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Effect of title IX of the Education Amendments of 1972. 83.5 Section 83.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972....

  1. 45 CFR 83.5 - Effect of title IX of the Education Amendments of 1972.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Effect of title IX of the Education Amendments of 1972. 83.5 Section 83.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972....

  2. 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.

  3. 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

  4. 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.

  5. Gene deletions in patients with haemophilia B and anti-factor IX antibodies.

    PubMed

    Giannelli, F; Choo, K H; Rees, D J; Boyd, Y; Rizza, C R; Brownlee, G G

    Christmas disease, or haemophilia B, is an inherited X-linked haemorrhagic disease which at present occurs in 798 known cases in the United Kingdom, corresponding to a frequency of about 1 in 30,000 males. Patients are deficient in the intrinsic clotting factor IX and are treated by replacement of this protein prepared from pooled plasma obtained from normal individuals. Occasionally treatment is complicated by the appearance of specific anti-factor IX antibodies. It seemed to us that this might be due to the absence of 'self' factor IX causing the immune system to regard the infused normal factor IX as foreign. The absence of all or part of the factor IX gene was an obvious possible reason for this, which we have now tested using our previously isolated gene probe. We have found four patients with gross gene defects.

  6. Molecular cloning of the gene for human anti-haemophilic factor IX.

    PubMed

    Choo, K H; Gould, K G; Rees, D J; Brownlee, G G

    1982-09-01

    A functional deficiency of factor IX, one of the coagulation factors involved in blood clotting, leads to the bleeding disorder known as Christmas disease, or haemophilia B. Both this disease and haemophilia A (factor VIII (C) deficiency) are X chromosome-linked and together occur at a frequency of approximately 1 in 10,000 males. The molecular basis for the functional alteration of factor IX in Christmas disease is not clearly understood. As a first step towards the elucidation of the molecular events involved, we have attempted molecular cloning of the factor IX gene. We used a bovine factor IX cDNA clone, isolated using synthetic oligonucleotides as probes, to screen a cloned human gene library. Here we report the isolation and partial characterization of a lambda recombinant phage containing the human factor IX gene.

  7. The Australian and New Zealand Haemostasis Registry: ten years of data on off-licence use of recombinant activated factor VII

    PubMed Central

    Zatta, Amanda; McQuilten, Zoe; Kandane-Rathnayake, Rangi; Isbister, James; Dunkley, Scott; McNeil, John; Cameron, Peter; Phillips, Louise

    2015-01-01

    Background Recombinant activated factor VII (rFVIIa) has been widely used as an off-licence pan-haemostatic agent in patients with critical bleeding. However, outside the trauma setting, there is relatively little high quality evidence on the risks and benefits of this agent. The Haemostasis Registry was established to investigate the extent of use, dosing, safety and outcomes of patients after off-licence rFVIIa treatment of critical bleeding. Materials and methods The Registry recruited non-haemophiliac patients treated with rFVIIa from 2000–2009 (inclusive) in Australia and New Zealand. Detailed information was gathered on patients’ demographics, context of bleeding, rFVIIa administration, laboratory results, blood component and other therapies, and outcomes. Outcome measures included subjectively assessed effect of rFVIIa on bleeding (response), adverse events (thromboembolic and other) and 28-day mortality. Results The registry included 3,446 cases in 3,322 patients (median [IQR] age 56 [33–70] years, 65% (n=2,147) male). Clinical indications included cardiac surgery (45%), other surgery (18%), trauma (13%), medical bleeding (6%), liver disease (6%), and obstetric haemorrhage (5%). The median [IQR] dose was 91 [72–103] μg/kg and 77% received a single dose. Reduction or cessation of bleeding was reported in 74% and 28-day survival was 71% but outcomes varied depending on clinical context. pH strongly correlated with outcome measures; 81% of patients with pH <7.1 died. Approximately 11% of patients had thromboembolic adverse events. In multivariate analysis, pH prior to administration and bleeding context were independently associated with reported response to rFVIIa and 28-day mortality. Discussion The Haemostasis Registry is the largest dataset of its kind and provides observational data on the off-licence use of rFVIIa over a 10-year period. It has been an invaluable resource for rigorously tracking adverse events and helping to inform clinical

  8. The decomposition of protoporphyrin IX by ultrasound is dependent on the generation of hydroxyl radicals.

    PubMed

    Xu, Haobo; Sun, Xin; Yao, Jianting; Zhang, Jian; Zhang, Yun; Chen, Haibo; Dan, Juhua; Tian, Zhen; Tian, Ye

    2015-11-01

    The ultrasound activation of certain drugs, such as porphyrins, could cause synergistic cytotoxic effects on cells. Both sonomechanical and sonochemical effects occur and the latter play a critical role because antioxidant agents could exert significant protective effects against the cytotoxicity. To investigate the reactive oxygen species involved in the sonochemical effects, aqueous protoporphyrin IX (PpIX) solutions were characterized under ultrasound sonication in this study. Inertial cavitation was indirectly evaluated using terephthalic acid dosimetry. The fluorescence intensity of the PpIX was measured using a fluorescence spectrophotometer. The effects of PpIX concentration, ultrasound parameters and free radical scavengers on the PpIX activation by ultrasound were investigated. Our results showed that the increase in PpIX decomposition was significantly correlated with cavitation activities (R=0.9874, p<0.05), and the decomposing effect increases with ultrasound intensity (0.6-1.5 W/cm(2)), initial PpIX concentration (1-5 μM), duty cycle (10-100%) and the sonication duration (2-10 min). The fluorescence and absorption spectra of PpIX showed a decrease in the peak intensity without spectral shifts or new peak build-up after sonication. The PpIX decomposition was significantly inhibited by hydroxyl radical scavengers, histidine, mannitol, acetone, methanol and ethanol, but the decomposition was not inhibited by sodium azide, catalase or superoxide dismutase. These results suggest that the decomposition of protoporphyrin IX by ultrasound is dependent on the generation of hydroxyl radicals, which sheds some light on the sonochemical effects of the interaction between ultrasound and porphyrins.

  9. 12 CFR 900.3 - Terms relating to other entities and concepts used throughout 12 CFR chapter IX.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to other entities and concepts used throughout 12 CFR chapter IX. As used throughout this chapter, the following terms relating to other entities and concepts used throughout 12 CFR chapter IX have the... used throughout 12 CFR chapter IX. 900.3 Section 900.3 Banks and Banking FEDERAL HOUSING FINANCE...

  10. 12 CFR 900.3 - Terms relating to other entities and concepts used throughout 12 CFR chapter IX.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... used throughout 12 CFR chapter IX. 900.3 Section 900.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD... to other entities and concepts used throughout 12 CFR chapter IX. As used throughout this chapter, the following terms relating to other entities and concepts used throughout 12 CFR chapter IX have...

  11. 12 CFR 900.3 - Terms relating to other entities and concepts used throughout 12 CFR chapter IX.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... used throughout 12 CFR chapter IX. 900.3 Section 900.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD... to other entities and concepts used throughout 12 CFR chapter IX. As used throughout this chapter, the following terms relating to other entities and concepts used throughout 12 CFR chapter IX have...

  12. 12 CFR 900.3 - Terms relating to other entities and concepts used throughout 12 CFR chapter IX.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... used throughout 12 CFR chapter IX. 900.3 Section 900.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD... to other entities and concepts used throughout 12 CFR chapter IX. As used throughout this chapter, the following terms relating to other entities and concepts used throughout 12 CFR chapter IX have...

  13. An Up-Close Look at Ares I-X

    NASA Technical Reports Server (NTRS)

    Leahy, Bart

    2010-01-01

    On October 28, 2009, one day later than the originally planned launch date, the Ares I-X suborbital test flight roared into the Florida sky. Flying its preplanned parabolic arc over the Atlantic, the development test vehicle for the Ares I crew launch vehicle performed as advertised, executing a perfect liftoff, 90-degree roll maneuver, ascent, and separation before its upper and lower stages descended into the ocean 150 miles downrange. This test flight, while carrying no astronauts, marked a major milestone for NASA, which had not flown a test launch of a human-rated rocket since the first flight of the Space Shuttle in 1981. During the flight, over 700 sensors collected over 900 measurements, which NASA will apply to validating the engineering models they used to design the vehicle in the first place. That data, telemetered to the ground and stored in a flight recorder onboard, was the primary "payload" of the mission.

  14. Flavobacterium gliding motility and the type IX secretion system.

    PubMed

    McBride, Mark J; Nakane, Daisuke

    2015-12-01

    Cells of Flavobacterium johnsoniae crawl rapidly over surfaces in a process called gliding motility. These cells do not have flagella or pili but instead rely on a novel motility machine composed of proteins that are unique to the phylum Bacteroidetes. The motility adhesins SprB and RemA are propelled along the cell surface by the still poorly-defined gliding motor. Interaction of these adhesins with a surface results in translocation of the cell. SprB and RemA are delivered to the cell surface by the type IX secretion system (T9SS). T9SSs are confined to but common in the phylum Bacteroidetes. Transmembrane components of the T9SS may perform roles in both secretion and gliding motility. PMID:26461123

  15. Protoporphyrin IX binding and transport by recombinant mouse PBR.

    PubMed

    Wendler, Gregor; Lindemann, Peter; Lacapère, Jean-Jacques; Papadopoulos, Vassilios

    2003-11-28

    The mitochondrial 18kDa peripheral-type benzodiazepine receptor (PBR), a high affinity cholesterol binding protein, has been shown to interact with protoporphyrin IX (PPIX) and this interaction was assumed to be involved in the regulation of heme biosynthesis and porphyrin-based photodynamic therapy in cancer. In order to test this hypothesis recombinant mouse PBR was expressed in Escherichia coli. The recombinant gene product showed in E. coli protoplasts specific affinity for PPIX binding. PPIX could displace PK 11195 binding. Moreover, induced PBR protein expression in E. coli protoplasts caused an uptake of PPIX that could be completely inhibited by cholesterol and to a lesser extent inhibited by PK 11195 and Ro5-4864. These results suggest that PBR, in addition to its role in cholesterol and coproporphyrinogen III transport, is also directing the mitochondrial PPIX import, a function that can be ascribed to the 18kDa PBR protein alone.

  16. Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum*

    PubMed Central

    Ramos, Rogério Rodrigo; Kozusny-Andreani, Dora Inês; Fernandes, Adjaci Uchôa; Baptista, Mauricio da Silva

    2016-01-01

    BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID:27192510

  17. Latex carrier for improving protoporphyrin IX for photodynamic therapy.

    PubMed

    Bui, Brian; Liu, Li; Chen, Wei

    2016-06-01

    Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer. PMID:27020668

  18. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

    PubMed Central

    Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-01-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P < .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274. PMID:26755710

  19. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

    PubMed

    Santagostino, Elena; Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-04-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.

  20. Exosite-mediated substrate recognition of factor IX by factor XIa. The factor XIa heavy chain is required for initial recognition of factor IX.

    PubMed

    Ogawa, Taketoshi; Verhamme, Ingrid M; Sun, Mao-Fu; Bock, Paul E; Gailani, David

    2005-06-24

    Studies of the mechanisms of blood coagulation zymogen activation demonstrate that exosites (sites on the activating complex distinct from the protease active site) play key roles in macromolecular substrate recognition. We investigated the importance of exosite interactions in recognition of factor IX by the protease factor XIa. Factor XIa cleavage of the tripeptide substrate S2366 was inhibited by the active site inhibitors p-aminobenzamidine (Ki 28 +/- 2 microM) and aprotinin (Ki 1.13 +/- 0.07 microM) in a classical competitive manner, indicating that substrate and inhibitor binding to the active site was mutually exclusive. In contrast, inhibition of factor XIa cleavage of S2366 by factor IX (Ki 224 +/- 32 nM) was characterized by hyperbolic mixed-type inhibition, indicating that factor IX binds to free and S2366-bound factor XIa at exosites. Consistent with this premise, inhibition of factor XIa activation of factor IX by aprotinin (Ki 0.89 +/- 0.52 microM) was non-competitive, whereas inhibition by active site-inhibited factor IXa beta was competitive (Ki 0.33 +/- 0.05 microM). S2366 cleavage by isolated factor XIa catalytic domain was competitively inhibited by p-aminobenzamidine (Ki 38 +/- 14 microM) but was not inhibited by factor IX, consistent with loss of factor IX-binding exosites on the non-catalytic factor XI heavy chain. The results support a model in which factor IX binds initially to exosites on the factor XIa heavy chain, followed by interaction at the active site with subsequent bond cleavage, and support a growing body of evidence that exosite interactions are critical determinants of substrate affinity and specificity in blood coagulation reactions. PMID:15829482

  1. Atomic data and spectral line intensities for Ca IX

    SciTech Connect

    Landi, E.; Bhatia, A.K.

    2014-11-15

    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, and 5 complexes, corresponding to 283 fine-structure levels in the 3l3l{sup ′}, 3l4l{sup ″}, and 3l5l{sup ‴} configurations, where l,l{sup ′}=s,p,d, l{sup ″}=s,p,d,f and l{sup ‴}=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 range of 10{sup 8}–10{sup 14}  cm{sup −3} and at an electron temperature of logT{sub e}(K)=5.8, corresponding to the maximum abundance of Ca IX. Spectral line intensities are calculated, and their diagnostic relevance is discussed.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX.

    PubMed

    Su, Xiaomin; Wang, Xiaobing; Zhang, Kun; Yang, Shuang; Liu, Quanhong; Leung, Albert W; Xu, Chuanshan; Wang, Pan

    2016-04-01

    Sonodynamic therapy (SDT) is expected to be a novel therapeutic strategy for tumor. The protoporphyrin IX disodium salt (PpIX), a photosensitizer, can be activated by ultrasound. The present study aims to investigate apoptosis of HL-60 cells induced by PpIX-mediated SDT. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to examine cell toxicity. Apoptosis was detected using Annexin V-PE/7-amino-actinomycin D (7-AAD) double staining. Detection of apoptotic bodies was examined by Hoechst33342 (HO) staining. Western blotting was used to analyze the protein of caspase-3 and poly ADP-ribose polymerase (PARP). Intracellular reactive oxygen species (ROS) was detected by a flow cytometer after exposures. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound were significantly boosted. In addition, as determined by Annexin V-PE/7-AAD staining, SDT significantly induced HL-60 cell apoptosis, the obvious nuclear condensation was also found with HO staining at 4 hours post-SDT treatment. Furthermore, Western blotting showed visible enhancement of caspase-3 and PARP cleavage in this process. Besides, intracellular ROS production was significantly enhanced after SDT. Our findings demonstrate that PpIX-mediated SDT could induce apoptosis on HL-60 cells, suggesting that apoptosis is an important mechanism of cell death induced by PpIX-mediated SDT. PMID:26891272

  8. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    SciTech Connect

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-05-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble /sup 3/H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl/sub 2/ (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of /sup 3/H preceded the appearance of Factor IXa activity, and the percentage of /sup 3/H released remained constant when the mole fraction of /sup 3/H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of /sup 3/H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant.

  9. 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.

  10. 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.

  11. 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.

  12. Delayed diagnosis of congenital factor IX deficiency (Christmas disease) in a girl with Turner's Syndrome.

    PubMed

    Kelsey, G; Monagle, P; Barnes, C

    2006-10-01

    Patients with Turner's syndrome are at risk of X-linked recessive disorders. We report a case of a young girl with Turner's syndrome with persistent mildly abnormal coagulation studies associated with a mild to moderate bleeding diathesis. The abnormalities were initially attributed to intrahepatic cholestasis and were partially responsive to vitamin K. After an interval of several years an episode of unexplained iron deficiency anaemia prompted re-investigation of the mild coagulopathy. Disproportionate reduction in the factor IX concentration and restoration of haemostasis with factor IX concentrate lead to a revised provisional diagnosis of mild haemophilia B which was subsequently confirmed by sequencing the factor IX gene.

  13. Type IX collagen knock-out mouse shows progressive hearing loss.

    PubMed

    Suzuki, Nobuyoshi; Asamura, Kenji; Kikuchi, Yasutake; Takumi, Yutaka; Abe, Satoko; Imamura, Yasutada; Hayashi, Toshihiko; Aszodi, Attila; Fässler, Reinhard; Usami, Shin-ichi

    2005-03-01

    Type IX collagen is one of the important components, together with type II, V, and XI collagens, in the tectorial membrane of the organ of Corti. To confirm the significance of type IX collagen for normal hearing, we assessed the detailed morphological and electrophysiological features of type IX collagen knock-out mice, which have recently been reported as a deafness model. Through assessment by auditory brainstem response (ABR), knock-out mice were shown to have progressive hearing loss. At the light microscopic level, the tectorial membrane of knock-out mice was found to be abnormal in shape. These morphological changes started in the basal turn and were progressive toward the apical turn. Electron microscopy confirmed disturbance of organization of the collagen fibrils. These results suggest that mutations in type IX collagen genes may lead to abnormal integrity of collagen fibers in the tectorial membrane.

  14. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S.

    PubMed

    Di Scipio, R G; Hermodson, M A; Yates, S G; Davie, E W

    1977-02-22

    Human prothrombin, factor IX, and factor X have been idolated in high yield and characterized as the their amino-terminal sequence, molecular weight, amino acid composition, and migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An additional human plasma protein, called protein S, has also been purified and its properties have been compared with those of prothrombin, factor IX, and factor X. Prothrombin (mol wt 72 000), factor IX (mol wt 57 000), and protein S (mol wt 69 000) are single-chain glycoproteins, while factor X (mol wt 59 000) is a glycoprotein composed of two polypeptide chains held together by a disulfide bond(s). The amino-terminal sequence of the light chain of human factor X is homologous with prothrombin, factor IX, and protein S. The heavy chain of human factor X is slightly larger than the heavy chain of bovine factor X and differs from bovine factor X in its amino-terminal sequence.

  15. Effect of stanozolol on factors VIII and IX and serum aminotransferases in haemophilia.

    PubMed

    Greer, I A; Greaves, M; Madhok, R; McLoughlin, K; Porter, N; Lowe, G D; Preston, F E; Forbes, C D

    1985-06-24

    The treatment of haemophilia has been dramatically improved since the introduction of factor VIII and IX concentrates, however these concentrates have brought new problems such as hepatitis and A.I.D.S. An oral agent which could raise endogenous levels of factor VIII and IX would be of great benefit. Danazol, an anabolic steroid, has recently been shown to increase levels of factors VIII and IX in haemophilia. We therefore studied the effect of stanozolol, a closely related anabolic steroid, in 15 patients with haemophilia A or Christmas disease over a 2-4 week period. There was no consistent change in factor VIIIc or factor IX, and fibrinolysis was significantly enhanced. No effect was apparent on the incidence of spontaneous bleeds. However serum aminotransferases which were abnormal in 11 of the 15 patients at the start of the study fell significantly with stanozolol therapy. This raises the interesting possibility that anabolic steroids may be beneficial in patients with chronic liver diseases.

  16. Protoporphyrin IX-β-cyclodextrin bimodal conjugate: nanosized drug transporter and potent phototoxin.

    PubMed

    Aggelidou, Chrysie; Theodossiou, Theodossis A; Yannakopoulou, Konstantina

    2013-01-01

    Topical or systemic administration of 5-aminolevulinic acid (ALA) and its esters results in increased production and accumulation of protoporphyrin IX (PpIX) in cancerous lesions allowing effective application of photodynamic therapy (PDT). The large concentrations of exogenous ALA practically required to bypass the negative feedback control exerted by heme on enzymatic ALA synthesis and the strong dimerization propensity of ALA are shortcomings of the otherwise attractive PpIX biosynthesis. To circumvent these limitations and possibly enhance the phototoxicity of PpIX by adjuvant chemotherapy, covalent bonding of PpIX with a drug carrier, β-cyclodextrin (βCD) was implemented. The resulting PpIX + βCD product had both carboxylic termini of PpIX connected to the CD. PpIX + βCD was water soluble, was found to preferentially localize in mitochondria rather than in lysosomes both in MCF7 and DU145 cell lines while its phototoxiciy was comparable to that of PpIX. Moreover, PpIX + βCD effectively solubilized the breast cancer drug tamoxifen metabolite N-desmethyltamoxifen (NDMTAM) in water. The PpIX + βCD/NDMTAM complex was readily internalized by both cell lines employed. Furthermore, the multimodal action of PpIX + βCD was demonstrated in MCF7 cells: while it retains the phototoxic profile of PpIX and its fluorescence for imaging purposes, PpIX + βCD can efficiently transport tamoxifen citrate intracellularly and confer cell death through a synergy of photo- and chemotoxicity. PMID:23819797

  17. 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.

  18. Activation of factor IX bound to cultured bovine aortic endothelial cells.

    PubMed Central

    Stern, D M; Drillings, M; Kisiel, W; Nawroth, P; Nossel, H L; LaGamma, K S

    1984-01-01

    Previous studies have shown that factor IX and its activated form, factor IXa, bind to cultured vascular endothelial cells and that cell-bound factor IXa retains its procoagulant activity. The present studies provide evidence that factor IX bound to cultured bovine aortic endothelial cells can be activated. Factor IX activation was assessed by finding cleavage of the factor IX molecule on NaDodSO4/polyacrylamide gel electrophoresis and by the generation of procoagulant activity as assessed by thrombin-treated factor VIII-dependent generation of factor Xa activity. Cell-bound factor IX (0.8 micrograms per 4 X 10(8) cells per ml) could be activated by factor XIa (5 micrograms/ml) or by factor VIIa (0.1 micrograms/ml) without exogenous tissue factor when endothelial cells were treated with phorbol ester and acquired tissue factor-like procoagulant activity. Regardless of how factor IX was activated, the cell-bound factor IXa required thrombin-treated factor VIII and calcium, but not exogenous phospholipid, to activate factor X. In further experiments, factor X bound to endothelial cells specifically and reversibly with a dependence on calcium and with a lower affinity (half-maximal at 480 nM) than factor IX. At saturation, 9.1 X 10(6) factor X molecules were bound per cell. After activation of factor X by factor IXa, approximately 50% of the factor Xa formed could be eluted from the cells by 10 mM EDTA, suggesting that the factor Xa was cell associated. These observations indicate that endothelial cells can bind and promote the activation of factors IX and X in the absence of platelets or exogenous phospholipid. PMID:6608105

  19. 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.

  20. Protoporphyrin IX nanoparticle carrier: preparation, optical properties, and singlet oxygen generation.

    PubMed

    Rossi, Liane M; Silva, Paulo R; Vono, Lucas L R; Fernandes, Adjaci U; Tada, Dayane B; Baptista, Maurício S

    2008-11-01

    The present study is focused on developing a nanoparticle carrier for the photosensitizer protoporphyrin IX for use in photodynamic therapy. The entrapment of protoporphyrin IX (Pp IX) in silica spheres was achieved by modification of Pp IX molecules with an organosilane reagent. The immobilized drug preserved its optical properties and the capacity to generate singlet oxygen, which was detected by a direct method from its characteristic phosphorescence decay curve at near-infrared and by a chemical method using 1,3-diphenylisobenzofuran to trap singlet oxygen. The lifetime of singlet oxygen when a suspension of Pp IX-loaded particles in acetonitrile was excited at 532 nm was determined as 52 micros, which is in good agreement with the value determined for methylene blue in acetonitrile solution under the same conditions. The Pp IX-loaded silica particles have an efficiency of singlet oxygen generation (eta Delta) higher than the quantum yield of free porphyrins. This high efficiency of singlet oxygen generation was attributed to changes on the monomer-dimer equilibrium after photosentisizer immobilization. PMID:18834155

  1. In vitro carboxylation of a blood coagulation factor IX precursor produced by recombinant-DNA technology.

    PubMed

    Soute, B A; Balland, A; Faure, T; de la Salle, H; Vermeer, C

    1989-04-25

    Blood coagulation factor IX (Christmas factor) is a plasma protein which is required for normal haemostasis. A functional deficiency of factor IX results in haemophilia B, a bleeding disorder which is generally treated by infusions of factor IX concentrates prepared from pooled human plasma. The use of human blood products is connected with the risk of transmitting viral agents responsible for diseases such as hepatitis B and AIDS. Recombinant DNA techniques may provide the means to produce the required proteins without exposing the patients to these risks and at lower costs. One of the problems which has to be overcome before recombinant factor IX can be used for therapeutical purposes is related to the vitamin K-dependent carboxylation of its 12 NH2-terminal glutamate residues. In cell cultures this carboxylation, which is required to render the protein its procoagulant activity, is far from complete, especially at high expression levels. In this paper we describe the in vitro carboxylation of non and/or partly carboxylated recombinant factor IX produced by transformed Chinese hamster ovary cells. The identity of the newly formed Gla residues was verified and it could be demonstrated that all carboxyl groups had been incorporated into the recombinant factor IX.

  2. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

    PubMed Central

    Lee, Meng-Hwan; Lin, Yin-Shen; Tu, Ching-Fu; Yen, Chon-Ho

    2014-01-01

    Production of biopharmaceuticals from transgenic animal milk is a cost-effective method for highly complex proteins that cannot be efficiently produced using conventional systems such as microorganisms or animal cells. Yields of recombinant human factor IX (rhFIX) produced from transgenic porcine milk under the control of the bovine α-lactalbumin promoter reached 0.25 mg/mL. The rhFIX protein was purified from transgenic porcine milk using a three-column purification scheme after a precipitation step to remove casein. The purified protein had high specific activity and a low ratio of the active form (FIXa). The purified rhFIX had 11.9 γ-carboxyglutamic acid (Gla) residues/mol protein, which approached full occupancy of the 12 potential sites in the Gla domain. The rhFIX was shown to have a higher isoelectric point and lower sialic acid content than plasma-derived FIX (pdFIX). The rhFIX had the same N-glycosylation sites and phosphorylation sites as pdFIX, but had a higher specific activity. These results suggest that rhFIX produced from porcine milk is physiologically active and they support the use of transgenic animals as bioreactors for industrial scale production in milk. PMID:24955355

  3. Finite Element Model Calibration Approach for Ares I-X

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

    Ares I-X is a pathfinder vehicle concept under development by NASA to demonstrate a new class of launch vehicles. Although this vehicle is essentially a shell of what the Ares I vehicle will be, efforts are underway to model and calibrate the analytical models before its maiden flight. Work reported in this document will summarize the model calibration approach used including uncertainty quantification of vehicle responses and the use of nonconventional boundary conditions during component testing. Since finite element modeling is the primary modeling tool, the calibration process uses these models, often developed by different groups, to assess model deficiencies and to update parameters to reconcile test with predictions. Data for two major component tests and the flight vehicle are presented along with the calibration results. For calibration, sensitivity analysis is conducted using Analysis of Variance (ANOVA). To reduce the computational burden associated with ANOVA calculations, response surface models are used in lieu of computationally intensive finite element solutions. From the sensitivity studies, parameter importance is assessed as a function of frequency. In addition, the work presents an approach to evaluate the probability that a parameter set exists to reconcile test with analysis. Comparisons of pre-test predictions of frequency response uncertainty bounds with measured data, results from the variance-based sensitivity analysis, and results from component test models with calibrated boundary stiffness models are all presented.

  4. Finite Element Model Calibration Approach for Area I-X

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

    Ares I-X is a pathfinder vehicle concept under development by NASA to demonstrate a new class of launch vehicles. Although this vehicle is essentially a shell of what the Ares I vehicle will be, efforts are underway to model and calibrate the analytical models before its maiden flight. Work reported in this document will summarize the model calibration approach used including uncertainty quantification of vehicle responses and the use of non-conventional boundary conditions during component testing. Since finite element modeling is the primary modeling tool, the calibration process uses these models, often developed by different groups, to assess model deficiencies and to update parameters to reconcile test with predictions. Data for two major component tests and the flight vehicle are presented along with the calibration results. For calibration, sensitivity analysis is conducted using Analysis of Variance (ANOVA). To reduce the computational burden associated with ANOVA calculations, response surface models are used in lieu of computationally intensive finite element solutions. From the sensitivity studies, parameter importance is assessed as a function of frequency. In addition, the work presents an approach to evaluate the probability that a parameter set exists to reconcile test with analysis. Comparisons of pretest predictions of frequency response uncertainty bounds with measured data, results from the variance-based sensitivity analysis, and results from component test models with calibrated boundary stiffness models are all presented.

  5. Thermal Model Development for Ares I-X

    NASA Technical Reports Server (NTRS)

    Amundsen, Ruth M.; DelCorso, Joe

    2008-01-01

    Thermal analysis for the Ares I-X vehicle has involved extensive thermal model integration, since thermal models of vehicle elements came from several different NASA and industry organizations. Many valuable lessons were learned in terms of model integration and validation. Modeling practices such as submodel, analysis group and symbol naming were standardized to facilitate the later model integration. Upfront coordination of coordinate systems, timelines, units, symbols and case scenarios was very helpful in minimizing integration rework. A process for model integration was developed that included pre-integration runs and basic checks of both models, and a step-by-step process to efficiently integrate one model into another. Extensive use of model logic was used to create scenarios and timelines for avionics and air flow activation. Efficient methods of model restart between case scenarios were developed. Standardization of software version and even compiler version between organizations was found to be essential. An automated method for applying aeroheating to the full integrated vehicle model, including submodels developed by other organizations, was developed.

  6. The lower cranial nerves: IX, X, XI, XII.

    PubMed

    Sarrazin, J-L; Toulgoat, F; Benoudiba, F

    2013-10-01

    The lower cranial nerves innervate the pharynx and larynx by the glossopharyngeal (CN IX) and vagus (CN X) (mixed) nerves, and provide motor innervation of the muscles of the neck by the accessory nerve (CN XI) and the tongue by the hypoglossal nerve (CN XII). The symptomatology provoked by an anomaly is often discrete and rarely in the forefront. As with all cranial nerves, the context and clinical examinations, in case of suspicion of impairment of the lower cranial nerves, are determinant in guiding the imaging. In fact, the impairment may be located in the brain stem, in the peribulbar cisterns, in the foramens or even in the deep spaces of the face. The clinical localization of the probable seat of the lesion helps in choosing the adapted protocol in MRI and eventually completes it with a CT-scan. In the bulb, the intra-axial pathology is dominated by brain ischemia (in particular, with Wallenberg syndrome) and multiple sclerosis. Cisternal pathology is tumoral with two tumors, schwannoma and meningioma. The occurrence is much lower than in the cochleovestibular nerves as well as the leptomeningeal nerves (infectious, inflammatory or tumoral). Finally, foramen pathology is tumoral with, outside of the usual schwannomas and meningiomas, paragangliomas. For radiologists, fairly hesitant to explore these lower cranial pairs, it is necessary to be familiar with (or relearn) the anatomy, master the exploratory technique and be aware of the diagnostic possibilities.

  7. Function of carbonic anhydrase IX in glioblastoma multiforme.

    PubMed

    Proescholdt, Martin A; Merrill, Marsha J; Stoerr, Eva-Maria; Lohmeier, Annette; Pohl, Fabian; Brawanski, Alexander

    2012-11-01

    Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma. PMID:23074198

  8. Ares I-X In-Flight Modal Identification

    NASA Technical Reports Server (NTRS)

    Bartkowicz, Theodore J.; James, George H., III

    2011-01-01

    Operational modal analysis is a procedure that allows the extraction of modal parameters of a structure in its operating environment. It is based on the idealized premise that input to the structure is white noise. In some cases, when free decay responses are corrupted by unmeasured random disturbances, the response data can be processed into cross-correlation functions that approximate free decay responses. Modal parameters can be computed from these functions by time domain identification methods such as the Eigenvalue Realization Algorithm (ERA). The extracted modal parameters have the same characteristics as impulse response functions of the original system. Operational modal analysis is performed on Ares I-X in-flight data. Since the dynamic system is not stationary due to propellant mass loss, modal identification is only possible by analyzing the system as a series of linearized models over short periods of time via a sliding time-window of short time intervals. A time-domain zooming technique was also employed to enhance the modal parameter extraction. Results of this study demonstrate that free-decay time domain modal identification methods can be successfully employed for in-flight launch vehicle modal extraction.

  9. Young drivers who obtained their licence after an intensive driving course report more incidents than drivers with a traditional driver education.

    PubMed

    de Craen, Saskia; Vlakveld, Willem P

    2013-09-01

    This paper studies the effectiveness of intensive driving courses; both in driving test success and safe driving after passing the driving test. The so-called intensive driving course (IDC) consists of a limited number of consecutive days in which the learner driver takes driving lessons all day long; and is different from traditional training in which lessons are spread out over several months and in which learners take one or two driving lessons of approximately 1 h each per week. Our study indicates that--in the first two years of their driving career--IDC drivers (n=35) reported an incident significantly more often (43%) than 351 drivers who obtained their driving licence after traditional training (26%). Our study also indicates that the IDC drivers underwent almost the same number of training hours as the drivers who had traditional training, although spacing of these hours was different. There was no difference in the number of attempts to pass the driving test. We did not find any evidence that a self-selection bias was responsible for the difference in reported number of incidents.

  10. Increases in fines and driver licence withdrawal have effectively reduced immediate deaths from trauma on Brazilian roads: first-year report on the new traffic code.

    PubMed

    Poli de Figueiredo, L F; Rasslan, S; Bruscagin, V; Cruz, R; Rocha e Silva, M

    2001-03-01

    Road accidents are a major cause of death in Brazil, with rates increasing steadily for years. Our objective here is to report the impact of the new Brazilian Traffic Code, introduced in 1998. Its main new features include a large increase in fines and a rigid penalty scoring system that leads to driver license withdrawal. Speed limits have actually been raised on many roads, but adherence to the rules has been monitored more closely. We compare the incidence of injured patients and immediate deaths in road accidents and emergency room admissions to a level I trauma centre in downtown São Paulo between January and December 1998 with corresponding data from between January and December 1997. There was an overall 21.3% reduction in the number of accidents and a 24.7% reduction in immediate deaths, saving 5962 lives on Brazilian highways. Tickets issued fell by 49.5% (601977 during 1997 to 304785 during 1998). Motor vehicle accident-related emergency room admissions decreased by 33.2%. We conclude that very costly tickets and threatened driver licences have proved very effective in decreasing immediate deaths from trauma. Further advances in educational programmes associated with road and vehicle safety measures are likely to provide the much needed further reduction in the still high trauma mortality on Brazilian roads and streets.

  11. 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.

  12. 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.

  13. Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of factor IX or fresh frozen plasma (FFP).

    PubMed

    Zauber, N P; Levin, J

    1977-05-01

    There has been no systematic re-examination of variables that may affect the level and duration of response of patients with hemophilia B (Christmas disease) to transfusion. Therefore, 49 of our transfusion episodes and 171 previously reported transfusions were evaluated. Mean calculated initial increase of Factor IX levels (delta %/unit (U) of procoagulant activity infused/kg) was 0.82 +/- 0.09% (mean +/-S.E.) in previously reported cases and 1.01 +/- 0.13% in our patients, after transfusion of concentrate; but only 0.05 +/- 0.11% after fresh frozen plasma (FFP). Response was not altered by acute hemorrhage, baseline Factor IX levels, or body weight. Proplex (Hyland) and Konyne (Cutter) produced similar responses. Following transfusion, the disappearance curve was biphasic. The mean T1/2 for the second component was 27.5 hrs, but the direct T1/2 was only 6.4 +/- 1.0 hr. Regardless of common clinical variables, increase of Factor IX following transfusion of American concentrates is 1.0% (or 0.01 U)/1 administered/kg. Appropriate frequency of transfusion depends upon an understanding of the biphasic disappearance of Factor IX. Importantly, the initial frequency of transfusion therapy should be based on a direct T1/2 of only 6 to 8 hrs.

  14. Histopathological Determinants of Tumor Resistance: A Special Look to the Immunohistochemical Expression of Carbonic Anhydrase IX in Human Cancers

    PubMed Central

    Ilardi, G.; Zambrano, N.; Merolla, F.; Siano, M.; Varricchio, S.; Vecchione, M.; De Rosa, G.; Mascolo, M.; Staibano, S.

    2014-01-01

    Intrinsic and acquired drug resistance of tumor cells still causes the failure of treatment regimens in advanced human cancers. It may be driven by intrinsic tumor cells features, or may also arise from micro environmental influences. Hypoxia is a microenvironment feature associated with the aggressiveness and metastasizing ability of human solid cancers. Hypoxic cancer cells overexpress Carbonic Anhydrase IX (CA IX). CA IX ensures a favorable tumor intracellular pH, while contributing to stromal acidosis, which facilitates tumor invasion and metastasis. The overexpression of CA IX is considered an epiphenomenon of the presence of hypoxic, aggressive tumor cells. Recently, a relationship between CA IX overexpression and the cancer stem cells (CSCs) population has been hypothesized. CSCs are strictly regulated by tumor hypoxia and drive a major non-mutational mechanism of cancer drug-resistance. We reviewed the current data concerning the role of CA IX overexpression in human malignancies, extending such information to the expression of the stem cells markers CD44 and nestin in solid cancers, to explore their relationship with the biological behavior of tumors. CA IX is heavily expressed in advanced tumors. A positive trend of correlation between CA IX overexpression, tumor stage/grade and poor outcome emerged. Moreover, stromal CA IX expression was associated with adverse events occurrence, maybe signaling the direct action of CA IX in directing the mesenchymal changes that favor tumor invasion; in addition, membranous/cytoplasmic co-overexpression of CA IX and stem cells markers were found in several aggressive tumors. This suggests that CA IX targeting could indirectly deplete CSCs and counteract resistance of solid cancers in the clinical setting. PMID:23992304

  15. 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.

  16. A New Peptide Ligand for Targeting Human Carbonic Anhydrase IX, Identified through the Phage Display Technology

    PubMed Central

    Askoxylakis, Vasileios; Garcia-Boy, Regine; Rana, Shoaib; Krämer, Susanne; Hebling, Ulrike; Mier, Walter; Altmann, Annette; Markert, Annette; Debus, Jürgen; Haberkorn, Uwe

    2010-01-01

    Carbonic anhydrase IX (CAIX) is a transmembrane enzyme found to be overexpressed in various tumors and associated with tumor hypoxia. Ligands binding this target may be used to visualize hypoxia, tumor manifestation or treat tumors by endoradiotherapy. Methods Phage display was performed with a 12 amino acid phage display library by panning against a recombinant extracellular domain of human carbonic anhydrase IX. The identified peptide CaIX-P1 was chemically synthesized and tested in vitro on various cell lines and in vivo in Balb/c nu/nu mice carrying subcutaneously transplanted tumors. Binding, kinetic and competition studies were performed on the CAIX positive human renal cell carcinoma cell line SKRC 52, the CAIX negative human renal cell carcinoma cell line CaKi 2, the human colorectal carcinoma cell line HCT 116 and on human umbilical vein endothelial cells (HUVEC). Organ distribution studies were carried out in mice, carrying SKRC 52 tumors. RNA expression of CAIX in HCT 116 and HUVEC cells was investigated by quantitative real time PCR. Results In vitro binding experiments of 125I-labeled-CaIX-P1 revealed an increased uptake of the radioligand in the CAIX positive renal cell carcinoma cell line SKRC 52. Binding of the radioligand in the colorectal carcinoma cell line HCT 116 increased with increasing cell density and correlated with the mRNA expression of CAIX. Radioligand uptake was inhibited up to 90% by the unlabeled CaIX-P1 peptide, but not by the negative control peptide octreotide at the same concentration. No binding was demonstrated in CAIX negative CaKi 2 and HUVEC cells. Organ distribution studies revealed a higher accumulation in SKRC 52 tumors than in heart, spleen, liver, muscle, intestinum and brain, but a lower uptake compared to blood and kidney. Conclusions These data indicate that CaIX-P1 is a promising candidate for the development of new ligands targeting human carbonic anhydrase IX. PMID:21209841

  17. The novel CA IX inhibition antibody chKM4927 shows anti-tumor efficacy in vivo.

    PubMed

    Yamaguchi, Ayami; Usami, Katsuaki; Shimabe, Munetake; Hasegawa, Kazumasa; Asada, Masao; Motoki, Kazuhiro; Tahara, Tomoyuki; Masuda, Kazuhiro

    2015-04-01

    Carbonic anhydrase IX (CA IX) is an attractive target for cancer therapy. Many anti-CA IX antibodies have been reported but few have been shown to possess inhibition activity. Furthermore, effective use of CA IX-inhibition antibodies for cancer immunotherapy has not been well-validated since data are mainly limited to in vitro assays. In this study, we established that chKM4927, an anti-CA IX chimeric antibody, recognizes CA IX and has CA IX-specific inhibition activity. ChKM4927 also retains antibody-dependent cellular cytotoxicity (ADCC) activity against CA IX-expressing cancer cells. Compared to controls, chKM4927 treatment (10 mg/kg) showed anti-tumor activity in the VMRC-RCW xenograft model in vivo. ChKM4927-attenuated ADCC activity showed equally effective anti-tumor activity. These results suggest that the CA IX-inhibition antibody chKM4927 has an anti-tumor effect in the VMRC-RCW xenograft model via an ADCC-independent mechanism. PMID:25862852

  18. Spontaneous disappearance of an IgA anti-factor IX inhibitor in a child with Christmas disease.

    PubMed

    Carroll, R R; Panush, R S; Kitchens, C S

    1984-10-01

    The few inhibitors to blood coagulation factor IX in patients with Christmas disease (hemophilia B) that have been studied have been shown to belong to the IgG class of immunoglobulins. We report the first case in which a factor IX inhibitor was of the IgA class. Additionally, he appears to be the youngest patient with hemophilia B to have developed an inhibitor. His inhibitor complicated treatment of the patient for several years because of its anamnestic rise following factor IX concentrate administration. It then spontaneously vanished and has not returned in spite of repeated factor IX complex administration.

  19. Ares I-X Roll Control System Development

    NASA Technical Reports Server (NTRS)

    Unger, Ronald J.; Massey, Edmund C.

    2009-01-01

    Project Managers often face challenging technical, schedule and budget issues. This presentation will explore how the Ares I-X Roll Control System Integrated Product Team (IPT) mitigated challenges such as concurrent engineering requirements and environments and evolving program processes, while successfully managing an aggressive project schedule and tight budget. IPT challenges also included communications and negotiations among inter- and intra-government agencies, including the US Air Force, NASA/MSFC Propulsion Engineering, LaRC, GRC, KSC, WSTF, and the Constellation Program. In order to successfully meet these challenges it was essential that the IPT define those items that most affected the schedule critical path, define early mitigation strategies to reduce technical, schedule, and budget risks, and maintain the end-product focus of an "unmanned test flight" context for the flight hardware. The makeup of the IPT and how it would function were also important considerations. The IPT consisted of NASA/MSFC (project management, engineering, and safety/quality) and contractors (Teledyne Brown Engineering and Pratt and Whitney Rocketdyne, who supplied heritage hardware experience). The early decision to have a small focused IPT working "badgelessly" across functional lines to eliminate functional stove-piping allowed for many more tasks to be done by fewer people. It also enhanced a sense of ownership of the products, while still being able to revert back to traditional roles in order to provide the required technical independence in design reviews and verification closures. This presentation will highlight several prominent issues and discuss how they were mitigated and the resulting Lessons Learned that might benefit other projects.

  20. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    PubMed Central

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H R

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that of normal Factor IXa beta. In the present study we have prepared activated Factor IX by incubating human Factor IX with calcium and Russell's viper venom covalently bound to agarose. Fractionation of the activated Factor IX by high-performance liquid chromatography demonstrated the presence of both Factors IXa alpha and IXa beta. On the basis of active site concentration, determined by titration with antithrombin III, the clotting activities of activated Factor IX Chapel Hill and IXa alpha were similar, but both activities were less than 20% of the clotting activity of Factor IXa beta. Activated Factor IX activity was also measured in the absence of calcium, phospholipid, and Factor VIII, by determination of the rate of Factor X activation in the presence of polylysine. In the presence of polylysine, the rates of Factor X activation by activated Factor IX Chapel Hill, Factor IXa alpha, and Factor IXa beta were essentially identical. We conclude that the clotting activity of activated Factor IX Chapel Hill is reduced when compared with that of Factor IXa beta but essentially normal when compared with that of Factor IXa alpha. PMID:3871202

  1. Fluorescence dynamics of ALA-induced PpIX in normal and malignant skin cells

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Stringer, Mark R.; Cruse-Sawyer, Janet E.; Brown, Stanley B.

    2003-10-01

    We have applied a spectroscopic system capable of monitoring the fluorescence dynamics of photosensitiser at micron-scale locations within individual cells. This report shows that the accumulation of protoporphyrin IX (PpIX) within the nucleus of formalin-fixed keratinocytes, fibroblasts, and a metastatic squamous carcinoma cell line, following incubation with 5-aminolaevulinic acid (ALA), is dependent upon both incubation time and cell proliferation status. We demonstrate that the process of photobleaching can be monitored via the depletion in PpIX fluorescence emission during exposure to 532 nm laser light. All spectra show a progressive reduction of the 634 nm PpIX peak - following a bi-exponential decay which is consistent with a singlet oxygen mediated process. The rate of photobleaching, when plotted as a function of light dose, increases with reduced incident laser power. The generation of the hydroxyaldehyde-chlorin photoproduct, as monitored by the increase in fluorescence emission centred on 672 nm, is also greatest when the lowest laser power is applied. When light is delivered in two fractions, there is evidence of PpIX fluorescence recovery during the dark period, and an increase in bleaching rate at the onset of the second exposure. These results are in qualitative agreement with measurements performed in vivo which demonstrate that the photodynamic dose is dependent upon fluence-rate and oxygen status.

  2. Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

    PubMed Central

    Rollakanti, Kishore R.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2014-01-01

    Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients. PMID:25599015

  3. Ares I-X Overview - The First Chapter in the Next Great Adventure

    NASA Technical Reports Server (NTRS)

    Leahy, Bart

    2008-01-01

    Ares I-X is the first flight of NASA's new Constellation Program. Ares I-X is a development test flight to provide engineering data to inform the design of the Ares I prior to CDR. Ares I will replace the Space Shuttle which is scheduled for 2010 retirement . Ares I-X is an uncrewed, sub-orbital development flight test . Ares I-X will provide opportunity to test ground facilities and operations at NASA's Kennedy Space Center. Ares I-X is on track for May 2009 launch date. Objectives include: (1) Demonstrate control of a dynamically similar, integrated Ares I/Orion, using Ares I relevant ascent control algorithms; (2) Perform an in-flight separation/staging event between a Ares I-similar First Stage and a representative Upper Stage; (3) Demonstrate assembly and recovery of a new Ares I-like First Stage element at KSC; (4) Demonstrate First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics, and parachute performance; and (5) Characterize magnitude of integrated vehicle roll torque throughout First Stage flight.

  4. Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX.

    PubMed

    Jaye, M; de la Salle, H; Schamber, F; Balland, A; Kohli, V; Findeli, A; Tolstoshev, P; Lecocq, J P

    1983-04-25

    A unique 52mer oligonucleotide deduced from the amino acid sequence of bovine Factor IX was synthesized and used as a probe to screen a human liver cDNA bank. The Factor IX clone isolated shows 5 differences in nucleotide and deduced amino acid sequence as compared to a previously isolated clone. In addition, precisely one codon has been deleted.Images

  5. Materials for Electroactive Ion-Exchange (EaIX) Separations of Pertechnetate Ion

    SciTech Connect

    Stender, Matthias; Hubler, Timothy L.; Alhoshan, Mansour; Smyrl, William H.

    2004-03-29

    Many contaminants of interest to the U.S. Department of Energy (DOE) exist as anions (e.g. chromate, pertechnetate and nitrate). The objective of this study is to develop Electroactive Ion-Exchange (EaIX) materials. Such materials can be used to separate pertechnetate ion from radioactive wastes located at DOE sites while limiting the amount of secondary wastes generated. We have developed a synthetic strategy to prepare vinyl-bipyridyl and -terpyridyl ligands which allow incorporation of ion-selective architectures with a polymerizable handle. Fe complexes formed with these ligands provide the working core of the electroactive polymers. The polymers can be directly used as materials for EaIX or they can be incorporated into porous composite materials that are then used for EaIX.

  6. Synthesis and biological evaluation of a new family of anti-benzylanilinosulfonamides as CA IX inhibitors.

    PubMed

    Thiry, Anne; Delayen, Aurélie; Goossens, Laurence; Houssin, Raymond; Ledecq, Marie; Frankart, Aurélie; Dogné, Jean-Michel; Wouters, Johan; Supuran, Claudiu T; Hénichart, Jean-Pierre; Masereel, Bernard

    2009-02-01

    We report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors prepared regio- and stereoselectively by reacting sulfanilamide with ethyl trans-phenylglycidate in the presence of cobalt(II) chloride. Various derivatizations of the ester moiety in the parent compound led to a small library of derivatives (2R,3R and 2S,3S) which displayed interesting inhibitory activities towards the human tumor-associated isoform CA IX. One of the new compounds shows high selectivity in inhibiting hCA IX compared to the two physiologically relevant, cytosolic isozymes hCA I and hCA II. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active sites of hCA IX and hCA II. PMID:18479784

  7. Interactions between collagen IX and biglycan measured by atomic force microscopy

    SciTech Connect

    Chen, C.-H.; Yeh, M.-L.; Geyer, Mark; Wang, Gwo-Jaw; Huang, M.-H.; Heggeness, Michael H.; Hoeoek, Magnus; Luo, Z.-P. . E-mail: luo@bcm.tmc.edu

    2006-01-06

    The stability of the lattice-like type II collagen architecture of articular cartilage is paramount to its optimal function. Such stability not only depends on the rigidity of collagen fibrils themselves, but more importantly, on their interconnections. One known interconnection is through type IX and biglycan molecules. However, the mechanical properties of this interaction and its role in the overall stability remain unrevealed. Using atomic force microscopy, this study directly measured the mechanical strength (or the rupture force) of a single bond between collagen IX and biglycan. The results demonstrated that the rupture force of this single bond was 15 pN, which was significantly smaller than those of other known molecule interactions to date. This result suggested that type IX collagen and biglycan interaction may be the weak link in the cartilage collagen architecture, vulnerable to abnormal joint force and associated with disorders such as osteoarthritis.

  8. Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib-IX complex clustering and signaling.

    PubMed

    Shang, Dan; Zhang, Zuping; Wang, Qian; Ran, Yali; Shaw, Tanner S; Van, John N; Peng, Yuandong

    2016-10-01

    Platelet glycoprotein Ib-IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP-280). We find that removal of the ABP-280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP-280 independent force may exist. Besides, we observe that the signaling upon GP Ib-IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib-IX function. © 2016 IUBMB Life, 68(10):823-829, 2016. PMID:27634617

  9. Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib-IX complex clustering and signaling.

    PubMed

    Shang, Dan; Zhang, Zuping; Wang, Qian; Ran, Yali; Shaw, Tanner S; Van, John N; Peng, Yuandong

    2016-10-01

    Platelet glycoprotein Ib-IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP-280). We find that removal of the ABP-280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP-280 independent force may exist. Besides, we observe that the signaling upon GP Ib-IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib-IX function. © 2016 IUBMB Life, 68(10):823-829, 2016.

  10. PREFACE: The IX Mexican Workshop on Particles and Fields

    NASA Astrophysics Data System (ADS)

    Amore, Paolo; Aranda, Alfredo; Bashir, Adnan; Mondragón, Myriam; Raya, Alfredo

    2006-05-01

    The IX Mexican Workshop on Particles and Fields was held in the beautiful city of Colima, in the South-West of Mexico, from 17-22 November 2003. The proceedings of the Workshop were delayed due to problems with a previous publisher, we are very grateful that Journal of Physics: Conference Series kindly agreed to publish the proceedings rapidly at this late stage. The Workshop aimed to cover, through invited lectures delivered by internationally known experts, the most recent developments in the field. There was also a series of short seminars as well as a poster session, which allowed the whole community to participate with their most recent research results. A special session was dedicated to awarding the Division Medal to Professor Benjamin Grinstein, from The University of California, San Diego, for his outstanding contributions to the field. This volume contains the written version of the material presented at the Workshop. The Workshop was attended by more than 100 participants, including faculty members, postdocs and graduate students. It was organized by the Particles and Fields Division of the Mexican Physical Society, and generously sponsored by several institutions: Universidad de Colima, Universidad Nacional Autónoma de México, Universidad Michoacana de San Nicolás Hidalgo, Centro de Investigaciones y Estudios Avanzados del IPN (CINVESTAV), Consejo Nacional de Ciencia y Tecnología (Conacyt). The Local Organizing Committee was integrated by Paolo Amore, Alfredo Aranda, Carlos Moisés Hernóndez Suórez (Director of the Physics Faculty), Arturo Gonzólez Larios, Enrique Farías Martínez, and Myriam Cruz Calvario, all from the University of Colima. The members of the National Organizing Committee were Adnan Bashir (IFM-UMSHN), Jens Erler (IF-UNAM), Heriberto Castilla Valdés (CINVESTAV-U.Zacatenco), Gabriel López Castro (CINVESTAV-U.Zacatenco), Myriam Mondragón (IF-UNAM) and Luis Villaseñ or (IFM-UMSHN). We gratefully acknowledge the help given by

  11. Properties and environment of the molecular complex near Holmberg IX

    NASA Astrophysics Data System (ADS)

    Boone, F.; Brouillet, N.; Hüttemeister, S.; Henkel, C.; Braine, J.; Bomans, D. J.; Herpin, F.; Banhidi, Z.; Albrecht, M.

    2005-01-01

    This paper is aimed at providing new insight into the nature and origin of the molecular complex situated near the line of sight toward Holmberg IX in the M 81 group of galaxies. The first high resolution CO maps of the complex as well as single dish 13CO(1-0), 12CO(3-2) and millimeter continuum observations and the results of a survey of 12CO in the region are presented. These data together with the available HI, optical and X-ray observations are analyzed to study the properties and environment of the complex. We confirm there is no unobscured massive star formation inside the complex, and from the millimeter constraint on the extinction it must have a low star formation rate or be forming only low mass stars. According to the CO line ratios the abundances and physical conditions could be similar to that of cold gas in spirals. We find from its dynamics (no rotation) and its mass (2-6 million solar masses) that it resembles a massive GMC. Also, re-inspecting N-body simulations of the M 81 group and the H I data we find that it might be located inside the extreme outer disk of M 81 and be cospatial with the H I feature known as Concentration I. The negative result of the CO survey suggests that the complex is unique in this region and calls for a peculiar local formation process. We find that the distribution of the CO emission in the data cube is asymmetrical in a way similar to a cometary object. The optical observations of the nearby supershell MH9/10 suggest the existence of an outflow toward the complex. We consider the possibility that the molecular complex is related to this hypothetical outflow. Based on observations carried out with the IRAM Plateau de Bure Interferometer and 30 m telescope, the 10 m Heinrich-Hertz-Telescope (HHT), and the NRAO 12 m telecsope. IRAM (Institut de Radio-Astronomie Millimétrique) is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). The HHT was operated by the Submillimeter Telescope Observatory on behalf of

  12. 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.

  13. 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.

  14. 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

  15. Lacerations to Zones VIII and IX: It Is Not Just a Tendon Injury

    PubMed Central

    Fischer, Charla R.; Tang, Peter

    2011-01-01

    Extensor tendon injuries are widely believed to be straightforward problems that are relatively simple to manage. However, these injuries can be complex and demand a thorough understanding of anatomy to achieve the best functional outcomes. When lacerations occur in the forearm as in Zones VIII and IX injury, the repair of the extensor tendon and muscle, and posterior interosseous nerve (PIN) is often challenging. A review of the literature shows little guidance and attention for these injuries. We present four patients with injuries to Zones VIII and IX as well as a review of surgical technique, postoperative rehabilitation, and pearls that may be of benefit to those managing these injuries. PMID:21991409

  16. Organization within the cranial IX-X complex in ranid frogs: a horseradish peroxidase transport study.

    PubMed

    Stuesse, S L; Cruce, W L; Powell, K S

    1984-01-20

    Cranial nerves IX and X in frogs have been described as originating from a nuclear group referred to as the IX-X complex. We studied the central nervous system components of this complex in Rana pipiens and R. catesbiana by labeling peripheral branches of cranial nerves IX and X and identifying the central nervous system contributions of these branches. Various peripheral nerves (IX and the cardiac, gastric, pulmonary, and laryngeal branches of X) were identified and soaked in horseradish peroxidase (HRP). One to 2 weeks later, the frogs were killed and processed for HRP by the tetramethylbenzidine method. Glossopharyngeal efferents originated from a small ventrolateral cell group found at the level of IX root exit. Vagal efferents formed a single column of cells in a ventrolateral position from the level of the brainstem exist of the vagus nerve (approximately 2,000 micrometers above the obex) to 200 micrometers below the obex (values given are for an 80-g frog). This cell group was separate from and just caudal to efferent cells of the glossopharyngeal nerve. Within the vagal portion of the column, cells projecting through the gastric branch were found throughout the rostral-caudal extent of the nucleus. "Cardiac" cells tended to be more rostral than "pulmonary" cells, and both groups of cells were located in the middle of the nucleus. "Laryngeal" cells were located more caudally in the nucleus. This peripheral representation within the vagal nucleus corresponds more closely to the organization found in the mammalian nucleus ambiguus, rather than to the apparent lack of organization found in the mammalian dorsal motor nucleus. Afferents of IX and X entered slightly rostral to the ventral roots of their respective nerves and descended in two tracts. The majority entered the tractus solitarius and descended in a medial position to cervical spinal cord. A portion of the afferents from the vagus nerve crossed the midline in the lower myelencephalon just dorsal to the

  17. Concurrent acquired inhibitors to factor VIII and IX, a laboratory artifact: a case report

    PubMed Central

    Doma, Saša Anžej; Hillarp, Andreas; Pajič, Tadej; Andoljšek, Dušan; Černelč, Peter; Preldžnik Zupan, Irena

    2016-01-01

    Acquired inhibitors to coagulation factors other than factor VIII are extremely rare. We describe a case of a 59-year-old woman with abnormal bleeding, diagnosed with concurrent inhibitor antibodies to factor VIII and IX by Bethesda testing. We demonstrate that anti-FVIII antibodies of a very high titre are capable of disturbing the aPTT-based Bethesda assay, resulting in falsely-positive antibodies to factor IX. The case also illustrates the usefulness of the immunological assay (ELISA) in complementing the inhibitor diagnosis. PMID:27346976

  18. Collaborative study for the establishment of replacement batches for human coagulation factor IX concentrate reference standards.

    PubMed

    Gray, E; Pickering, W; Hockley, J; Rigsby, P; Weinstein, M; Terao, E; Buchheit, K-H

    2008-12-01

    The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch 1, the World Health Organisation (WHO) 3rd International Standard, Human (IS, 96/854) and the FDA Standard for human blood coagulation Factor IX concentrate have been available since 1996, following their establishment by a common collaborative study. Due to dwindling stocks of all three standards, a new WHO-EDQM-FDA tri-partite collaborative study was launched to establish replacement batches. Thirty laboratories from fourteen countries took part in the collaborative study to assign potency values to candidate preparations. Three candidates, one of recombinant and two of human plasma-derived origins, were assayed against the 3rd IS for Blood Coagulation Factor IX, Concentrate, Human (96/854). The 3rd IS for Blood Coagulation Factors II, VII, IX and X, Plasma, Human (99/826) was also included to evaluate the relationship between the factor IX plasma and concentrate unitage. Thirty-two sets of clotting assay results and two sets of chromogenic assay data were analysed. There was a significant difference in potency estimates by these two methods for the recombinant candidate (sample B) and the plasma IS (sample P). Similar potency values were obtained for the plasma derived products (monoclonal antibody- and chromatography-purified factor IX, samples C and D) by clotting and chromogenic assays. For the clotting assays, intra-laboratory variability (GCV) was found to range from 0.5 - 21.7%, with the GCV for the majority of laboratories being less than 10%. Good inter-laboratory agreement, with the majority of the GCV being less than 10% (GCV range = 4.7 - 10.6 %) was also obtained. The mean potency values estimated by the clotting assay using plasma as pre-diluent (as directed by the Ph. Eur. general chapter method) did not differ from values obtained using buffer. Taking into account the preliminary stability data, the intra- and inter-laboratory variability, and the differences

  19. In-flight motor torque estimates for the second-stage Strypi IX launch vehicle

    SciTech Connect

    Edmunds, R.S.

    1988-01-01

    This paper documents the results of a study to determine the character of body fixed torques generated by the Anteres IIA motor, during second-stage burn of the Strypi IX launch vehicle. The Strypi IX is a two-stage spin-stabilized solid-propellant launch vehicle designed to boost a variety of payloads to reentry environment conditions. The torque estimates were determined from postflight analysis of Euler angle telemetry data. Principal axis misalignments, and thrust misalignments were also estimated. Data was analyzed from two separate launches; a Precursor and a Prime flight. 21 figs.

  20. An investigation of three patients with Christmas disease due to an abnormal type of factor IX.

    PubMed

    Denson, K W; Biggs, R; Mannucci, P M

    1968-03-01

    Three patients with Christmas disease whose plasma was shown to have a prolonged one-stage prothrombin time with ox brain thromboplastin have been investigated. These patients have an inhibitor for the reaction between factor X, factor VII, and ox brain extract. The abnormal constituent responsible for this inhibitor appears to be factor IX whuch is functionally inactive but antigenically indistinguishable from normal factor IX. It is proposed that patients might be classified into haemophilia B(+) for patients with this defect (Christmas disease(+)) and haemophilia B(-) (Christmas disease(-)) for patients who have classical Christmas disease.

  1. A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor).

    PubMed

    Fujikawa, K; Coan, M H; Enfield, D L; Titani, K; Ericsson, L H; Davie, E W

    1974-02-01

    A comparison has been made of the electrophoretic behavior, chemical composition, amino-terminal sequence, and immunological properties of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor). Some immunological crossreactivity was found between the antibody to prothrombin and factor X although prothrombin and factor X differ substantially in amino-acid and carbohydrate composition. Considerable amino-acid sequence homology was found in the amino-terminal portion of prothrombin, factor IX, and the light chain of factor X. These data provide further evidence to support the hypothesis that at least three of the vitamin K-dependent clotting factors have evolved from a common ancestral gene.

  2. Inhibitor-neutralisation assay and electro-immuno assay of human factor IX (Christmas factor).

    PubMed

    Bertina, R M; van der Linden, I K

    1977-06-15

    A rabbit antibody specifically precipitating human factor IX has been used in the assay of factor IX antigen. The results obtained with two different methods (inhibitor-neutralisation assay and electro-immunoassay) have been compared in a group of healthy individuals and in a group of hemophilia B patients and carriers. In general, identical results are obtained with both methods, except in some hemophilia B+ carriers and patients, where the electroimmuno assay gives 1.5-2.0 times higher levels. Results obtained by electroimmuno assay are more accurate and reproducible than those obtained by inhibitor-neutralisation assay, which is of importance for its potential use in carrier detection.

  3. "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…

  4. Clearance of protoporphyrin IX from mouse skin after topical application of 5-aminolevulinic acid and its methyl ester

    NASA Astrophysics Data System (ADS)

    Juzenas, Petras; Sorensen, Roar; Iani, Vladimir; Moan, Johan

    1999-02-01

    The clearance of protoporphyrin IX (PpIX) from the skin of hairless BALB/c mice after topical application of 5- aminolevulinic acid (ALA) and its methyl ester (ALA-Me) was investigated. Creams containing 2 or 20% of ALA or ALA-Me were topically applied on spots of approximately 1 cm2 for 12 hours. The PpIX fluorescence was detected by the means of a Perkin Elmer LS50B luminescence spectrometer equipped with a fiber-optic probe. The emission spectrum was identical with that of cell-bound PpIX. After 12 hours application of ALA and ALA-Me similar amounts of PpIX were found. After creme removal the ALA-induced PpIX fluorescence decayed with a half-life of about 20 hours (20% ALA cream). The ALA-Me-induced PpIX was faster cleared from the skin than ALA-induced PpIX, and had a half-life of about 7 hours (20% ALA-Me cream).

  5. 40 CFR Appendix Ix to Part 86 - Experimentally Determining the R-Factor for Bench Aging Durability Procedures

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Factor for Bench Aging Durability Procedures IX Appendix IX to Part 86 Protection of Environment... the R-Factor for Bench Aging Durability Procedures The R-Factor is the catalyst thermal reactivity coefficient used in the bench aging time (BAT) equation . Manufacturers may determine the value of...

  6. 40 CFR Appendix Ix to Part 86 - Experimentally Determining the R-Factor for Bench Aging Durability Procedures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Factor for Bench Aging Durability Procedures IX Appendix IX to Part 86 Protection of Environment...-Factor for Bench Aging Durability Procedures The R-Factor is the catalyst thermal reactivity coefficient used in the bench aging time (BAT) equation . Manufacturers may determine the value of R...

  7. 40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B) IX Appendix IX to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS...

  8. 78 FR 79498 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Open-IX Association

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... Association Notice is hereby given that, on December 3, 2013, pursuant to Section 6(a) of the National... Association (``Open-IX'') has filed written notifications simultaneously with the Attorney General and the... and principal place of business of the standards development organization is: Open-IX...

  9. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)

    SciTech Connect

    Taylor, S.A.M.; Deugau, K.V.; Lillicrap, D.P. )

    1991-01-01

    Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which {gt}95% are single nulceotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. The authors used differential termination of primer extension to confirm and measure the degree of mosaicism. The study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factor IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male.

  10. 77 FR 34033 - American River Power IX, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-08

    ...--Hydroelectric Water Power Project (Peoria Dam Project or project) to be located at the U.S. Army Corps of... Energy Regulatory Commission American River Power IX, LLC; Notice of Preliminary Permit Application..., 2012, American River Power IX, LLC filed an application for a preliminary permit, pursuant to section...

  11. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).

    PubMed

    Taylor, S A; Deugau, K V; Lillicrap, D P

    1991-01-01

    Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which greater than 95% are single nucleotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. We used differential termination of primer extension to confirm and measure the degree of mosaicism. Our study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factor IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male.

  12. Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.

    PubMed

    Jagadeeswaran, P; Lavelle, D E; Kaul, R; Mohandas, T; Warren, S T

    1984-09-01

    Hemophilia B or Christmas disease is an X-linked condition caused by absent or reduced levels of functional coagulation factor IX. Based upon the peptide sequence of bovine factor IX, we synthesized a 17-base pair oligonucleotide probe to screen a human liver cDNA library. A recombinant clone was identified with a 917-nucleotide insert whose sequence corresponds to 70% of the coding region of human factor IX. This factor IX cDNA was used to probe restriction endonuclease digested human DNA to identify a Taq I polymorphism associated with the genomic factor IX gene as well as to verify that there is a single copy of this gene per haploid genome. The factor IX cDNA was also used to map the locus for factor IX to a region from Xq26 to Xqter. The cloning of human factor IX cDNA and identification of a Taq I polymorphism and its regional localization will provide a means to study the molecular genetics of hemophilia B and permit linkage analysis with nearby loci.

  13. Alprolix (recombinant Factor IX Fc fusion protein): extended half-life product for the prophylaxis and treatment of hemophilia B.

    PubMed

    Ducore, Jonathan M; Miguelino, Maricel G; Powell, Jerry S

    2014-10-01

    Hemophilia B is a genetic disease caused by mutation of the gene for coagulation protein Factor IX. When severe, the disease leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing Factor IX. Alprolix™ (recombinant Factor IX Fc fusion protein), is a therapeutic Factor IX preparation that has been engineered for a prolonged half-life in circulation, has completed pivotal clinical trials and has been approved recently in the USA, Canada, Australia and Japan for use in the clinic for patients with hemophilia B. This promising therapy should allow patients to use fewer infusions to maintain appropriate Factor IX activity levels in all clinical settings, and its use may be indicated in both on demand and prophylactic treatments.

  14. A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

    SciTech Connect

    Kim, Jung D.; Seo, Kwang W.; Lee, Eun A.; Quang, Nguyen N.; Cho, Hong R.; Kwon, Byungsuk

    2011-07-01

    Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

  15. Syntheses of protoporphyrin-IX derivatives bearing extended propionate side-chains.

    PubMed

    Holmes, Robert T; Lu, Jianming; Mwakwari, Celinah; Smith, Kevin M

    2009-05-29

    In order to investigate the relationship between depth within membranes of singlet oxygen generation and effectiveness of photodynamic therapy of tumors, analogs of protoporphyrin-IX 1 bearing five 4 and seven 5 carbon atoms (in place of the 3-carbon atom chain in 1) were synthesized from monopyrrole precursors.

  16. 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…

  17. User's Guide to Developing Student Interest Surveys Under Title IX. NCES 2005-173

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2005

    2005-01-01

    The purpose of this report is to provide a guide for conducting a survey of student interest in order to satisfy Part 3 the Three-Part Test established in the 1979 Policy Interpretation of the intercollegiate athletic provisions of Title IX of the Higher Education Act of 1972. To lay the foundation for the guide, NISS conducted an historical…

  18. Title IX, Girls' Sports Participation, and Adult Female Physical Activity and Weight

    ERIC Educational Resources Information Center

    Kaestner, Robert; Xu, Xin

    2010-01-01

    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…

  19. 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

  20. Flourescence analysis of ALA-induced Protoporphyrin IX in psoriatic plaque

    NASA Astrophysics Data System (ADS)

    Stringer, Mark R.; Robinson, Dominic J.; Collins, P.

    1996-01-01

    The success reported for the treatment of superficial skin carcinomas by photodynamic therapy (PDT), following topical application of 5-aminolaevulinic acid (ALA), has therapeutic implications for the treatment of other skin disorders. This presentation describes the accumulation of the photosensitizing agent protoporphyrin IX (PpIX) in areas of psoriatic plaque, by monitoring the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present the results from 15 patients, with a total of 42 plaques. These results show that PpIX fluorescence increases in intensity within the 6 hour period following application of ALA, which implies there is a potential for PDT. The emission is localized to the area of ALA application and the effect of occlusion appears insignificant. Also, the rate of increase, and maximum intensity of fluorescence emission, is not directly related to the applied quantity of ALA. The variability of the fluorescence intensity is as great between plaques at different sites on the same patient as between different patients. We also present measurements of the depletion in intensity of fluorescence emission during PDT treatment, using white light, at an irradiance of 25 mW cm-2, that is a consequence of the molecular photo-oxidation of PpIX. The use of fluorescence measurements in predicting the therapeutic effect of treating plaque psoriasis by ALA-PDT is discussed.

  1. A Title IX Perspective on the Schools' Response to Teenage Pregnancy and Parenthood.

    ERIC Educational Resources Information Center

    Zellman, Gail L.

    Title IX mandates that pregnant students, regardless of marital status, have the same rights and responsibilities as other students. Because social pressures on pregnant and parenting students to leave school still exists, schools have been required to develop responses to their needs. To examine these responses and subsequent programs from the…

  2. 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

    2010-01-01

    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.

  3. Title IX and Retaliation: The Impact of "Jackson v. Birmingham Board of Education" on Higher Education

    ERIC Educational Resources Information Center

    Melear, Kerry Brian

    2007-01-01

    In 2005, the United States Supreme Court rendered a closely divided opinion that extends the protections against discrimination provided by Title IX of the Education Amendments of 1972 to include a private cause of action for retaliation in "Jackson v. Birmingham Board of Education." Therefore, "whistleblowers," or employees who report allegedly…

  4. Specific immunohistochemical pattern of carbonic anhydrase IX is helpful for the diagnosis of CNS hemangioblastoma.

    PubMed

    Schaller, Tina; Bode, Markus; Berlis, Ansgar; Frühwald, Michael C; Lichtmannegger, Ines; Endhardt, Katharina; Märkl, Bruno

    2015-07-01

    Hemangioblastomas are rare capillary-rich tumors predominantly found in the CNS. The histological appearance of these tumors varies across a broad spectrum. Several entities show considerable histomorphological similarities to hemangioblastomas. Therefore, morphological evaluation can be challenging. In this study, we evaluated the diagnostic utility of immunohistochemistry using antibodies against carbonic anhydrase IX and cytokeratin staining. Within our files, we identified 20 hemangioblastomas. A collection of 46 other tumors relevant to the differential diagnosis (12 pilocytic astrocytomas, 11 meningiomas, one pleomorphic xanthoastrocytoma, one angiomatous fibrous histiocytoma, 14 carcinoma metastases and seven gliomas grades II-IX) served as control. The pattern of strong, diffuse expression of carbonic anhydrase IX with membranous accentuation in combination with keratin negativity was considered diagnostic for hemangioblastomas. It was found in 18 out of 20 (90%) hemangioblastomas and in none of the control cases (P < 0.001). This resulted in a sensitivity of 90% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively. Carbonic anhydrase IX with cytokeratin is thus a highly sensitive and specific marker combination for hemangioblastomas. It is therefore very helpful in the diagnosis of these tumors and in their discrimination from other entities. PMID:25888144

  5. 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.

  6. Einstein-Weyl field equations in a Bianchi type-IX space-time

    SciTech Connect

    Kolassis, C.A.; Le Denmat, G.

    1984-07-15

    It is proved that there exists no solution of the combined gravitational-neutrino field equations in general relativity if the space-time metric admits a group of isometries of Bianchi type IX and the neutrino field has geodesic and shearfree rays.

  7. 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…

  8. 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 ...

  9. 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.

  10. The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas disease)

    PubMed

    Goldsmith, J M; Variakojis, D; Phair, J P; Green, D

    1987-06-01

    Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 +/- 17,976 (S.D.) versus 1,250 +/- 1,500 factor units/year, (p less than 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.

  11. Syntheses of protoporphyrin-IX derivatives bearing extended propionate side-chains.

    PubMed

    Holmes, Robert T; Lu, Jianming; Mwakwari, Celinah; Smith, Kevin M

    2009-05-29

    In order to investigate the relationship between depth within membranes of singlet oxygen generation and effectiveness of photodynamic therapy of tumors, analogs of protoporphyrin-IX 1 bearing five 4 and seven 5 carbon atoms (in place of the 3-carbon atom chain in 1) were synthesized from monopyrrole precursors. PMID:20161404

  12. Hierarchical coassembly of DNA–triptycene hybrid molecular building blocks and zinc protoporphyrin IX

    PubMed Central

    Kumari, Rina; Singh, Sumit; Monisha, Mohan; Bhowmick, Sourav; Roy, Anindya

    2016-01-01

    Summary Herein, we describe the successful construction of composite DNA nanostructures by the self-assembly of complementary symmetrical 2,6,14-triptycenetripropiolic acid (TPA)–DNA building blocks and zinc protoporphyrin IX (Zn PpIX). DNA–organic molecule scaffolds for the composite DNA nanostructure were constructed through covalent conjugation of TPA with 5′-C12-amine-terminated modified single strand DNA (ssDNA) and its complementary strand. The repeated covalent conjugation of TPA with DNA was confirmed by using denaturing polyacrylamide gel electrophoresis (PAGE), reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). The biologically relevant photosensitizer Zn PpIX was used to direct the hybridization-mediated self-assembly of DNA–TPA molecular building blocks as well as a model guest molecule within the DNA–TPA supramolecular self-assembly. The formation of fiber-like composite DNA nanostructures was observed. Native PAGE, circular dichroism (CD) and atomic force microscopy (AFM) have been utilized for analyzing the formation of DNA nanofibers after the coassembly. Computational methods were applied to discern the theoretical dimension of the DNA–TPA molecular building block of the nanofibers. A notable change in photocatalytic efficiency of Zn PpIX was observed when it was inside the TPA–DNA scaffold. The significant increase in ROS generation by Zn PpIX when trapped in this biocompatible DNA–TPA hybrid nanofiber may be an effective tool to explore photodynamic therapy (PDT) applications as well as photocatalytic reactions. PMID:27335759

  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. 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.

  15. Measurement and modelling of protoporphyrin IX photo-oxidation during superficial PDT

    NASA Astrophysics Data System (ADS)

    Robinson, Dominic J.; Stringer, Mark R.; Crum, William R.; Collins, P.

    1996-12-01

    The oxidation of photosensitizers during photodynamic therapy (PDT) has important implications for their therapeutic and diagnostic potential. The reduction in sensitizer concentration during illumination progressively reduces the effectiveness of therapy and, ultimately, limits the destruction of the host tissue. In the course of our studies of the effects of PDT upon superficial skin disorders, following topical application of 5- aminolaevulinic acid (ALA), we routinely record the surface fluorescence emission of protoporphyrin IX (PpIX) before, during, and after therapy, in order to monitor the sensitizer photo-oxidation. It is important, therefore, to establish that measurements made in this way are representative of the variation in sensitizer concentration throughout the illuminated volume. We have developed a time- dependent Monte-Carlo model to simulate PpIX photo-oxidation during either low intensity laser (488 nm) or white light irradiation of plaque psoriasis. We have assessed the effect of differences in the optical properties of tissue at sites on different patients prior to treatment, and the effect of these variations on the surface fluorescence signal detected during treatment, at sites within the same plaque. The results show that the PpIX fluorescence intensity recorded from plaque psoriasis is an accurate indicator of the relative concentration of the sensitizer and can be used as a direct comparison between different sites and different patients. Also, the reduction in fluorescence emission during PDT is an effective measure of the depletion in sensitizer concentration throughout the illuminated volume. These results illustrate that the light dose required to achieve significant PpIX photo-oxidation is significantly lower than that often adopted for the treatment of superficial skin conditions.

  16. 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

  17. Zinc protoporphyrin IX enhances chemotherapeutic response of hepatoma cells to cisplatin

    PubMed Central

    Liu, Yang-Sui; Li, Huan-Song; Qi, Dun-Feng; Zhang, Jun; Jiang, Xin-Chun; Shi, Kui; Zhang, Xiao-Jun; Zhang, Xin-Hui

    2014-01-01

    AIM: To investigate the effect of zinc protoporphyrin IX on the response of hepatoma cells to cisplatin and the possible mechanism involved. METHODS: Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by a flow cytometric assay. Western blotting was used to measure protein expression. Heme oxygenase (HO)-1 activity was measured by determining the level of bilirubin generated in isolated microsomes. Reactive oxygen species (ROS) production was monitored by flow cytometry. Caspase-3 activity was measured with a colorimetric assay kit. Mice were inoculated with 1 × 107 tumor cells subcutaneously into the right flanks. All mice were sacrificed 6 wk after the first treatment and tumors were weighed and measured. RESULTS: Overexpression of HO-1 in HepG2 cell line was associated with increased chemoresistance to cis-diaminedichloroplatinum (cisplatin; CDDP) compared to other cell lines in vitro. Inhibition of HO-1 expression or activity by zinc protoporphyrin IX (ZnPP IX) markedly augmented CDDP-mediated cytotoxicity towards all liver cancer cell lines in vitro and in vivo. In contrast, induction of HO-1 with hemin increased resistance of tumor cells to CDDP-mediated cytotoxicity in vitro and in vivo. Furthermore, cells treated with ZnPP IX plus CDDP exhibited marked production of intracellular ROS and caspase-3 activity, which paralleled the incidence of cell apoptosis, whereas hemin decreased cellular ROS and caspase-3 activity induced by CDDP. CONCLUSION: ZnPP IX increases cellular sensitivity and susceptibility of liver cancer cell lines to CDDP and this may represent a mechanism of increasing ROS. PMID:25024611

  18. Avidin-based targeting and purification of a protein IX-modified, metabolically biotinylated adenoviral vector.

    PubMed

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

    2004-06-01

    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 (K(d) = 10(-15) M). The biotinylated vector could also be purified by biotin-reversible binding on monomeric avidin (K(d) = 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.

  19. Expression of human factor IX in rat capillary endothelial cells: Toward somatic gene therapy for hemophilia B

    SciTech Connect

    Shounan Yao; Wilson, J.M.; Nabel, E.G.; Kurachi, Sumiko; Hachiya, H.L.; Kurachi, Kotoku )

    1991-09-15

    In aiming to develop a gene therapy approach for hemophilia B, the authors expressed and characterized human factor IX in rat capillary endothelial cells (CECs). Moloney murine leukemia virus-derived retrovirus vectors that contain human factor IX cDNA linked to heterologous promoters and the neomycin-resistant gene were constructed and employed to prepare recombinant retroviruses. Rat CECs and NIH 3T3 cells infected with these viruses were selected with the neomycin analogue, G418 sulfate, and tested for expression of factor IX. A construct with the factor IX cDNA under direct control by long terminal repeat gave the highest level of expression as quantitated by immunoassays as well as clotting activity assays. A single RNA transcript of 4.4 kilobases predicted by the construct and a recombinant factor IX were found. The recombinant human factor IX produced showed full clotting activity, demonstrating that CECs have an efficient mechanism for posttranslational modifications, including {gamma}-carboxylation, essential for its biological activity. These results, in addition to other properties of the endothelium, including large number of cells, accessibility, and direct contact with the circulating blood, suggest that CECs can serve as an efficient drug delivery vehicle producing factor IX in a somatic gene therapy for hemophilia B.

  20. Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

    SciTech Connect

    Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

    2011-11-25

    We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: > We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. > Cre/loxP recombination was used to modify the adenovirus genome. > A targeting ligand present on capsid protein IX was removed or replaced using recombination. > Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

  1. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use.

    PubMed

    Pastorek, Jaromir; Pastorekova, Silvia

    2015-04-01

    The tumor microenvironment includes a complicated network of physiological gradients contributing to plasticity of tumor cells and heterogeneity of tumor tissue. Hypoxia is a key component generating intratumoral oxygen gradients, which affect the cellular expression program and lead to therapy resistance and increased metastatic propensity of weakly oxygenated cell subpopulations. One of the adaptive responses of tumor cells to hypoxia involves the increased expression and functional activation of carbonic anhydrase IX (CA IX), a cancer-related cell surface enzyme catalyzing the reversible conversion of carbon dioxide to bicarbonate ion and proton. Via its catalytic activity, CA IX participates in regulation of intracellular and extracellular pH perturbations that result from hypoxia-induced changes in cellular metabolism producing excess of acid. Through the ability to regulate pH, CA IX also facilitates cell migration and invasion. In addition, CA IX has non-catalytic function in cell adhesion and spreading. Thus, CA IX endows tumor cells with survival advantages in hypoxia/acidosis and confers an increased ability to migrate, invade and metastasize. Accordingly, CA IX is expressed in a broad range of tumors, where it is associated with prognosis and therapy outcome. Its expression pattern and functional implications in tumor biology make CA IX a promising therapeutic target, which can be hit either by immunotherapy with monoclonal antibodies or with compounds inhibiting its enzyme activity. The first strategy has already reached the clinical trials, whereas the second one is still in preclinical testing. Both strategies indicate that CA IX can become a clinically useful anticancer target, but urge further efforts toward better selection of patients for immunotherapy and deeper understanding of tumor types, clinical situations and synthetic lethality interactions with other treatment approaches.

  2. 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.

  3. An unusual complication in a gravida with factor IX deficiency: case report with review of the literature.

    PubMed

    Guy, G P; Baxi, L V; Hurlet-Jensen, A; Chao, C R

    1992-09-01

    Factor IX deficiency (hemophilia B, Christmas disease) is an X-linked recessive coagulation disorder. It occurs in one out of every 25,000-30,000 male births and requires even rarer genetic circumstances for phenotypic expression in females. We report the occurrence of a large, late-trimester subchorionic hematoma in a gravida with factor IX deficiency and with laboratory evidence of consumptive coagulopathy during treatment. The patient was managed conservatively and had a successful outcome at term. The only four reported cases of antepartum management of factor IX deficiency in the English literature are reviewed.

  4. Exact solutions of the Bianchi types V and IX via time-dependent quasi-Maxwell equations

    NASA Astrophysics Data System (ADS)

    Yavari, Morteza

    2014-02-01

    The exact solutions of the Einstein field equations for the Bianchi types V and IX in presence of a perfect fluid via the time-dependent quasi-Maxwell (TQM) equations are investigated by using the threading formalism.

  5. Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles.

    PubMed

    Rodrigues, Phamilla Gracielli Sousa; Campos de Menezes, Priscila Fernanda; Fujita, Alessandra Keiko Lima; Escobar, André; Barboza de Nardi, Andrigo; Kurachi, Cristina; Bagnato, Vanderlei S

    2015-09-01

    Photodynamic therapy (PDT) is used for skin treatments of premalignant and cancer lesions and recognized as a non-invasive technique that combines tissue photosensitization and subsequent exposure to light to induce cell death. However, it is limited to the treatment of superficial lesions, mainly due to the low cream penetration. Therefore, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedles rollers of 0.5, 1.0 and 1.5 mm length were investigated. An improvement in homogeneity and production of PpIX was shown in a porcine model. Widefield fluorescence imaging three hours after the topical application of ALA-cream in the combined treatment with microeedles rollers. PMID:25319567

  6. 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

  7. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with Schiff's bases incorporating iminoureido moieties.

    PubMed

    Singasane, Namrata; Kharkar, Prashant S; Ceruso, Mariangela; Supuran, Claudiu T; Toraskar, Mrunmayee P

    2015-12-01

    A series of new Schiff's bases was obtained from the sulfanilamide semicarbazone (4-aminosulfonylphenyl semicarbazide) and aromatic/heterocyclic aldehydes. The new compounds were designed to incorporate moieties known to induce effective inhibitory activity against carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in crucial physiologic or pathologic processes such as the cytosolic CA I and II or the transmembrane, tumor-associated CA IX and XII: the compounds were medium potency - weak CA I inhibitors, highly effective, low nanomolar CA II inhibitors, but few of them inhibited effectively CA IX and XII. This may probably due to the long spacer between the sulfamoylphenyl and imine fragments of the molecules, which probably induces a highly flexible conformation of the inhibitor bound to the active site of the enzyme, with destabilizing effects for the adduct. The detailed structure activity relationship for this class of inhibitors is discussed. PMID:25744513

  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. SULFUR IX TO XIII SPECTRAL MEASURMENTS BETWEEN 170 AND 500 A

    SciTech Connect

    Yang, Z. H.; Zhang, B. L.; Wang, W.; Yu, D.Y.; Cai, X. H.; Du, S. B.; Zeng, X. T.; Chang, H. W.

    2009-04-15

    This paper reports laboratory measurements of the spectrum of highly ionized sulfur. The spectrum of S IX-S XIII has been observed in the wavelength range 170-500 A. A total of 54 lines have been measured. Forty-two of them have been classified as 2s {sup 2}2p{sup k} -2s2p{sup k} {sup +1} and 2s2p{sup k} -2p{sup k} {sup +1} transitions. Twelve other lines have been ascribed to 2s-2p, 4p-5s, 5p-6s, 5d-6p, and 6p-8d transitions. These spectral lines have been identified, among which 22 are new and accurately measured. The analysis of the spectra was based on a comparison with other experimental results and calculated values.

  10. Genetic algorithm prediction of crystal structure of metastable Si-IX phase

    SciTech Connect

    Nguyen, Manh Cuong; Zhao, Xin; Wang, Yangang; Wang, Cai-Zhuang; Ho, Kai-Ming

    2013-12-14

    We performed genetic algorithm search for the atomic structure of the long Lime unsolved Si-IX phase. We found two new structures with space groups of P4(2)/m and P-4, respectively, which have lattice parameters in excellent agreement with the experimental data. The phonon calculations showed that the P4(2)/m structure exhibits a soft phonon mode, while the P-4 structure is dynamically stable. Our calculation also showed that the P-4 structure is a meta-stable structure in a pressure range from 0 to 40 GPa, The Si-IX phase could be a mixed phase consisting of the P4(2)/m and the P-4 structures. Published by Elsevier Ltd.

  11. 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.

  12. 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

  13. Characterisation of organic matter in IX and PACl treated wastewater in relation to the fouling of a hydrophobic polypropylene membrane.

    PubMed

    Myat, Darli T; Mergen, Max; Zhao, Oliver; Stewart, Matthew B; Orbell, John D; Gray, Stephen

    2012-10-15

    Extensive organic characterisation of a wastewater using liquid chromatography with a photodiode array and fluorescence spectroscopy (Method A), and UV(254) and organic carbon detector (Method B) was undertaken, as well as with fluorescence excitation emission spectroscopy (EEM). Characterisation was performed on the wastewater before and after ion exchange (IX) treatment and polyaluminium chlorohydrate (PACl) coagulation, and following microfiltration of the wastewater and pre-treated wastewaters. Characterisation by EEM was unable to detect biopolymers within the humic rich wastewaters and was not subsequently used to characterise the MF permeates. IX treatment preferentially removed low molecular weight (MW) organic acids and neutrals, and moderate amounts of biopolymers in contrast to a previous report of no biopolymer removal with IX. PACl preferentially removed moderate MW humic and fulvic acids, and large amounts of biopolymers. PACl showed a great preference for removal of proteins from the biopolymer component in comparison to IX. An increase in the fluorescence response of tryptophan-like compounds in the biopolymer fraction following IX treatment suggests that low MW neutrals may influence the structure and/or inhibit aggregation of organic compounds. Fouling rates for IX and PACl treated wastewaters had high initial fouling rates that reduced to lower fouling rates with time, while the untreated Eastern Treatment Plant (ETP) wastewater displayed a consistent, high rate of fouling. The results for the IX and PACl treated wastewaters were consistent with the long-term fouling rate being determined by cake filtration while both pore constriction and cake filtration contributed to the higher initial fouling rates. Higher rejection of biopolymers was observed for PACl and IX waters compared to the untreated ETP water, suggesting increased adhesion of biopolymers to the membrane or cake layer may lead to the higher rejection.

  14. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors

    PubMed Central

    Sedlakova, Olga; Svastova, Eliska; Takacova, Martina; Kopacek, Juraj; Pastorek, Jaromir; Pastorekova, Silvia

    2013-01-01

    Acidic tissue microenvironment contributes to tumor progression via multiple effects including the activation of angiogenic factors and proteases, reduced cell-cell adhesion, increased migration and invasion, etc. In addition, intratumoral acidosis can influence the uptake of anticancer drugs and modulate the response of tumors to conventional therapy. Acidification of the tumor microenvironment often develops due to hypoxia-triggered oncogenic metabolism, which leads to the extensive production of lactate, protons, and carbon dioxide. In order to avoid intracellular accumulation of the acidic metabolic products, which is incompatible with the survival and proliferation, tumor cells activate molecular machinery that regulates pH by driving transmembrane inside-out and outside-in ion fluxes. Carbonic anhydrase IX (CA IX) is a hypoxia-induced catalytic component of the bicarbonate import arm of this machinery. Through its catalytic activity, CA IX directly participates in many acidosis-induced features of tumor phenotype as demonstrated by manipulating its expression and/or by in vitro mutagenesis. CA IX can function as a survival factor protecting tumor cells from hypoxia and acidosis, as a pro-migratory factor facilitating cell movement and invasion, as a signaling molecule transducing extracellular signals to intracellular pathways (including major signaling and metabolic cascades) and converting intracellular signals to extracellular effects on adhesion, proteolysis, and other processes. These functional implications of CA IX in cancer are supported by numerous clinical studies demonstrating the association of CA IX with various clinical correlates and markers of aggressive tumor behavior. Although our understanding of the many faces of CA IX is still incomplete, existing knowledge supports the view that CA IX is a biologically and clinically relevant molecule, exploitable in anticancer strategies aimed at targeting adaptive responses to hypoxia and/or acidosis

  15. Proposal and demonstration of lambda-based internet exchange (IX) point using GMPLS protocols and photonic cross-connect (PXC)

    NASA Astrophysics Data System (ADS)

    Tsuritani, Takehiro; Okamoto, Shuichi; Ogino, Nagao; Otani, Tomohiro; Tanaka, Hideaki

    2004-10-01

    This paper proposes an architecture of a next-generation Internet eXchange (IX) based on the Generalized Multi-Protocol Label Switching (GMPLS) technologies and the photonic cross-connect (PXC), hereafter referred to a Lambda-IX. At first, we investigate a basic Lambda-IX model where the PXC provides a GMPLS-controlled lambda label-switched path (LSP) to interconnect different ISPs' border routers. We verify that the proposed Lambda-IX model can achieve the lambda-based and resilient interconnection for the ISPs, thanks to the PXC's bit-rate insensitive operation as well as fast restoration operation. In addition, once GMPLS functionalities are introduced on the border routers as well as the PXC, very flexible interconnection can be achieved such as demand-based creation and deletion of lambda LSPs. Next, we initiatively demonstrate an experimental Lambda-IX using a PXC and IP/MPLS routers. A Lambda-LSP with OC-192 bandwidth can be successfully created by using the GMPLS RSVP-TE signaling protocol via a control plane, and an EGP session of Border Gateway Protocol 4 (BGP-4) can be established over the Lambda-LSP created between the GMPLS-enabled border routers via a data plane. We also evaluate the fault recovery operation in the case where such Lambda-IXs are consisted of several PXCs and demonstrate that the Lambda-LSP as well as the corresponding BGP session can be restored with a fast recovery time of less than 1s. Through these investigation and demonstration, it is revealed that the Lambda-IX can be put to practical use aiming at inter-exchanging a large traffic in a near future, while enriching the functions of IX.

  16. Calibration and Flight Results for the Ares I-X 5-Hole Probe

    NASA Technical Reports Server (NTRS)

    Campbell, Joel F.; Brandon, Jay M.

    2011-01-01

    Flight and calibration results are presented for the Ares I-X 5-hole probe. The probe is calibrated by using a combination of wind tunnel, CFD, and other numerical modeling techniques. This is then applied to the probe flight data and comparisons are made between the vanes and 5-hole probe. Using this and other data it is shown the probe was corrupted by water rendering that measurement unreliable.

  17. Activation of clotting factors XI and IX in patients with acute myocardial infarction.

    PubMed

    Minnema, M C; Peters, R J; de Winter, R; Lubbers, Y P; Barzegar, S; Bauer, K A; Rosenberg, R D; Hack, C E; ten Cate, H

    2000-11-01

    In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.

  18. Monochromatic observations of Comet Tago-Sato-Kosaka 1969g /1969IX/

    NASA Technical Reports Server (NTRS)

    Rahe, J.; Mccracken, C. M.; Hallam, K. L.; Donn, B. D.

    1976-01-01

    Isophotes have been determined from 10 narrow-band filter photographs of Comet Tago-Sato-Kosaka 1969g (1969IX) taken between Feb. 11 and 14, 1970. The five interference filters used were centered on the CN band sequence at 3383A, the C2 band sequence at 4737A and 5165A, the C3 sequence at 4050A, and the continuum at 5300A. Gradients of intensity in various directions from the nucleus have been derived from the isophotes.

  19. A New Resin Glycoside, Muricatin IX, from the Seeds of Ipomoea muricata.

    PubMed

    Ono, Masateru; Taketomi, Saki; Kakiki, Yuichi; Yasuda, Shin; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro

    2016-01-01

    A new resin glycoside, named muricatin IX (1), was isolated from the seeds of Ipomoea muricata (L.) JACQ. (Convolvulaceae). The structure of 1 was determined on the basis of spectroscopic data as well as chemical evidence. Compound 1 is the first representative of resin glycosides in which an organic acid connects the sugar moiety and the aglycone moiety to form macrocyclic ester ring. PMID:27581646

  20. Christmas factor: dosage compensation and the production of blood coagulation factor IX.

    PubMed

    FROTA-PESSOA, O; GOMES, E L; CALICCHIO, T R

    1963-01-25

    The amount of factor IX (Christmas factor) for different genotypic classes was determined by means of a variant of the thromboplastin generation test. The mean value for females heterozygous for the Christmas gene was about half the mean values for normal males and for normal homozygous females; means for the latter two groups were about equal. This dosage compensation is interpreted as evidence in support of Lyon's hypothesis, according to which one X chromosome is inactive in mammalian females.

  1. 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.

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

    PubMed

    Pinard, Melissa A; Aggarwal, Mayank; Mahon, Brian P; Tu, Chingkuang; McKenna, Robert

    2015-10-01

    Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO2 to HCO3(-), 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-based 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, an Rcryst of 18.0% and an Rfree of 21.2%. 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.

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

    PubMed

    Pinard, Melissa A; Aggarwal, Mayank; Mahon, Brian P; Tu, Chingkuang; McKenna, Robert

    2015-10-01

    Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO2 to HCO3(-), 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-based 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, an Rcryst of 18.0% and an Rfree of 21.2%. 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. PMID:26457530

  4. Formation of protoporphyrin IX in mouse skin after topical application of 5-aminolevulinic acid and its methyl esther

    NASA Astrophysics Data System (ADS)

    Sorensen, Roar; Juzenas, Petras; Iani, Vladimir; Moan, Johan

    1999-02-01

    Normal skin of nude mice (Balb/c) was treated topically with 5-aminolevulinic acid (ALA) and its methyl ester (ALA-Me) for 24 hours. Approximately 0.1 gram of freshly prepared cream was applied to a spot of 1 cm2 on the flank of the mice, which was then covered with a transparent dressing. The ALA induced protoporphyrin IX (PpIX) was studied by means of a noninvasive fiber-optic fluorescence probe connected to a luminescence spectrometer. The excitation wavelength was 407 nm, and the emission wavelength was 637 nm. For the first hour a slight lag in PpIX production was observed for the mice treated with ALA-Me compared to the mice treated with ALA. After approximately 12 hours the ALA and the ALA-Me treated mice showed the same PpIX fluorescence intensity. From 12 hours until 24 hours the PpIX fluorescence intensity decreased for both treatment modalities, even though ALA and ALA-Me were continuously present. At 24 hours ALA-Me-treated mice had less than half the amount of PpIX in their skin compared with ALA- treated mice.

  5. Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models

    PubMed Central

    Chen, Liu Qi; Howison, Christine M.; Spier, Catherine; Stopeck, Alison T.; Malm, Scott W.; Pagel, Mark D.; Baker, Amanda F.

    2015-01-01

    The expression of carbonic anhydrase (CA IX) and it’s relation to acidosis in lymphomas has not been widely studied. We investigated the protein expression of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos, and Granta 519 lymphoma cell lines and tumor models, while also investigating the relation with hypoxia. An imaging method, acidoCEST MRI, was used to estimate lymphoma xenograft extracellular pH (pHe). Our results showed that clinical lymphoma tissues and cell line models in vitro and in vivo had moderate CA IX expression. Although in vitro studies showed that CA IX expression was induced by hypoxia, in vivo studies did not show this correlation. Untreated lymphoma xenograft tumor pHe had acidic fractions, and an Acidity Score was qualitatively correlated with CA IX expression. Therefore, CA IX is expressed in B-cell lymphomas and is qualitatively correlated with extracellular acidosis in xenograft tumor models. PMID:25130478

  6. In-vitro study on ALA-induced endogenous protoporphyrin IX as photosensitizer for photodynamic tumor diagnosis and therapy

    NASA Astrophysics Data System (ADS)

    Ueberriegler, K.; Fiedler, D.; Verwanger, Thomas; Schnitzhofer, Gerlinde; Banieghbal, E.; Krammer, Barbara E.

    1998-07-01

    Photodynamic tumor diagnosis and therapy is efficiently carried out by endogenous protoporphyrin IX as photosensitizer, induced by external addition of the precursor 5-aminolevulinic acid (ALA). In the present study, PpIX localization and photodynamically induced damage was investigated in normal and transformed human fibroblasts. PpIX formation reaches its maximum after incubation for at least 20 h with 700 (mu) g/m1 ALA, and increases with the pH- value. ALA has to be given 20-30 times more than external PpIX in order to produce the same cytotoxic damage. As detected by Low Light Imaging, PpIX is generated in the mitochondria, released to the cytoplasm and distributed to cytoplasma and nuclear membranes.The nucleus is not stained. Intracellular targets of PpIX damage after irradiation are mainly mitochondria, ER and nuclear membrane. The organelles show a decomposition pattern, which resembles apoptotic morphology and occurs faster in the co-cultivated transformed than in the normal cells. ALA-treated hepatocytes produce micronuclei and chromosomal aberrations, which indicates some mutagenic potential. Expression studies of the (proto)oncogenes c-myc and bcl-2 sublethally treated fibroblasts by quantitative RT-PCR show high deviations from the constitutive expression level, which are accompanied by cell cycle disturbances, indicating a possible precursor role to apoptosis introduction.

  7. Construction and radiolabeling of adenovirus variants that incorporate human metallothionein into protein IX for analysis of biodistribution.

    PubMed

    Liu, Lei; Rogers, Buck E; Aladyshkina, Natalia; Cheng, Bing; Lokitz, Stephen J; Curiel, David T; Mathis, J Michael

    2014-01-01

    Using adenovirus (Ad)-based vectors is a promising strategy for novel cancer treatments; however, current tracking approaches in vivo are limited. The C-terminus of the Ad minor capsid protein IX (pIX) can incorporate heterologous reporters to monitor biodistribution. We incorporated metallothionein (MT), a low-molecular-weight metal-binding protein, as a fusion to pIX. We previously demonstrated 99mTc binding in vitro to a pIX-MT fusion on the Ad capsid. We investigated different fusions of MT within pIX to optimize functional display. We identified a dimeric MT construct fused to pIX that showed significantly increased radiolabeling capacity. After Ad radiolabeling, we characterized metal binding in vitro. We explored biodistribution in vivo in control mice, mice pretreated with warfarin, mice preimmunized with wild-type Ad, and mice that received both warfarin pretreatment and Ad preimmunization. Localization of activity to liver and bladder was seen, with activity detected in spleen, intestine, and kidneys. Afterwards, the mice were euthanized and selected organs were dissected for further analysis. Similar to the imaging results, most of the radioactivity was found in the liver, spleen, kidneys, and bladder, with significant differences between the groups observed in the liver. These results demonstrate this platform application for following Ad dissemination in vivo. PMID:25060486

  8. 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.

  9. Type XII collagen. A large multidomain molecule with partial homology to type IX collagen.

    PubMed

    Gordon, M K; Gerecke, D R; Dublet, B; van der Rest, M; Olsen, B R

    1989-11-25

    Three overlapping cDNAs encoding alpha 1 (XII) collagen have been isolated and sequenced. The DNAs define five sequence domains within the chain. Three domains are nontriple-helical; two are relatively short triple-helical regions. The amino acid sequences of tryptic peptides derived from 16- and 10-kDa pepsin-resistant fragments isolated from tendon extracts are in full agreement with the deduced sequences of the triple-helical regions. Two of the five sequence domains in alpha 1 (XII), one triple-helical and one nontriple-helical, show a high degree of similarity to regions in type IX collagen chains. In addition, examination of seven exons in the alpha 1 (XII) gene shows that the gene is, in part, similar to the structure of type IX collagen genes. Therefore, collagen types IX and XII are partially homologous. The alpha 1 (XII) sequence data predict an asymmetric structure for type XII collagen molecules, fully consistent with the rotary shadowing images. These images show a triple-helical 75-nm tail attached through a central globule to three finger-like structures, each 60 nm long (Dublet, B., Oh, S., Sugrue, S. P., Gordon, M. K., Gerecke, D. R., Olsen, B. R., and van der Rest, M. (1989) J. Biol. Chem. 264, 13150-13156).

  10. [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. PMID:17955397

  11. Role of enhanced half-life factor VIII and IX in the treatment of haemophilia.

    PubMed

    Mahdi, Ali J; Obaji, Samya G; Collins, Peter W

    2015-06-01

    Treatment of congenital haemophilia with factor VIII and IX concentrates often requires frequent infusions. This has obvious implications in establishing effective administration strategies and, in turn, adherence. To overcome these issues, three main technologies--polyethylene-glycol, Fc-neonatal IgG1 and albumin fusion products--have emerged into various stages of clinical development. Published data indicates an approximately 1·5- and fivefold increase in half-life of factor VIII and IX, respectively, compared to standard recombinant concentrates. Studies into efficacy and safety are starting to be published. Monitoring and optimal use of these new concentrates remains unknown. Weekly factor IX prophylaxis appears to be a feasible prophylactic regimen in haemophilia B patients. Weekly longer-acting FVIII is unlikely to provide adequate prophylaxis in most patients with haemophilia A but may reduce the frequency of infusions. Ongoing clinical trials and real life experience will help shape how these products can be used in practice and their cost effectiveness. The drive for convenience however should not overshadow the ultimate goal of prophylaxis, namely, preventing bleeding and arthropathy.

  12. Soluble diamagnetic model for malaria pigment: coordination chemistry of gallium(III)protoporphyrin-IX.

    PubMed

    Bohle, D Scott; Dodd, Erin L; Pinter, Tyler B J; Stillman, Martin J

    2012-10-15

    The facile axial ligand exchange properties of gallium(III) protoporphyrin IX in methanol solution were utilized to explore self-association interactions by NMR techniques. Structural changes were observed, as well as competitive behavior with the ligands acetate and fluoride, which differed from that seen with the synthetic analogue gallium(III) octaethylporphyrin which lacks acid groups in its side-chains and has less solution heterogeneity as indicated by absorption and MCD spectroscopies. The propionic acid side chains of protoporphyrin IX are implicated in all such interactions of PPIX, and both dynamic metal-propionic interactions and the formation of propionate-bridged dimers are observed. Fluoride coordination provides an unusual example of slow ligand exchange, and this allows for the identification of a fluoride bridged dimer in solution. An improved synthesis of the chloride and hydroxide complexes of gallium(III) protoporphyrin IX is reported. An insoluble gallium analogue of hematin anhydride is described. In general, the interactions between solvent and the metal are found to confer very high solubility, making [Ga(PPIX)](+) a useful model for ferric heme species.

  13. Leishmania major possesses a unique HemG-type protoporphyrinogen IX oxidase

    PubMed Central

    Zwerschke, Dagmar; Karrie, Simone; Jahn, Dieter; Jahn, Martina

    2014-01-01

    Leishmania major was proposed to either utilize haem from its host or partially synthesize the tetrapyrrole from host provided precursors. However, only indirect evidence was available for this partial late haem biosynthetic pathway. Here, we demonstrate that the LMJF_06_1280 gene of L. major encodes a HemG-type PPO (protoporphyrinogen IX oxidase) catalysing the oxidation of protoporphyrinogen IX to protoporphyrin IX. Interestingly, trypanosomatids are currently the only known eukaryotes possessing HemG-type enzymes. The LMJF_06_1280 gene forms a potential transcriptional unit with LMJF_06_1270 encoding CPO (coproporphyrinogen III oxidase) and with LMJF_06_1290 for a cytochrome b5. In vivo function of the L. major hemG gene was shown by the functional complementation of the Escherichia coli ΔhemG strain LG285. Restored haem formation in E. coli was observed using HPLC analyses. Purified recombinant L. major HemG revealed PPO activity in vitro using different ubiquinones and triphenyltetrazolium as electron acceptors. FMN was identified as the L. major HemG cofactor. Active site residues were found to be essential for HemG catalysis. These data in combination with the solved crystal structures of L. major CPO and the physiological proof of a ferrochelatase activity provide clear-cut evidence for a partial haem biosynthetic pathway in L. major. PMID:24962471

  14. [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.

  15. A computational study of ligand binding affinities in iron(III) porphine and protoporphyrin IX complexes.

    PubMed

    Durrant, Marcus C

    2014-07-01

    The search for novel anti-malarial drugs that can disrupt biomineralization of ferriprotoporphyrin IX to haemozoin requires an understanding of the fundamental chemistry of the porphyrin's iron(iii) centre at the water-lipid interface. Towards this end, the binding affinities for a diverse set of 31 small ligands with iron(iii) porphine have been calculated using density functional theory, in the gas phase and also with implicit solvent corrections for both water and n-octanol. In addition, the binding of hydroxide, chloride, acetate, methylamine and water to ferriprotoporphyrin IX has been studied, and very similar trends are observed for the smaller and larger models. Anionic ligands generally give stronger binding than neutral ones; the strongest binding is observed for RO(-) and OH(-) ligands, whilst acetate binds relatively weakly among the anions studied. Electron-rich nitrogen donors tend to bind more strongly than electron-deficient ones, and the weakest binding is found for neutral O and S donors such as oxazole and thiophene. In all cases, ligand binding is stronger in n-octanol than in water, and the differences in binding energies for the two solvents are greater for ionic ligands than for neutrals. Finally, dimerization of ferriprotoporphyrin IX by means of iron(iii)-carboxylate bond formation has been modelled. The results are discussed in terms of haemozoin crystal growth and its disruption by known anti-malarial drugs.

  16. SOLPS modeling of the ORNL helicon and PhIX experiments

    NASA Astrophysics Data System (ADS)

    Owen, L. W.; Peng, Y. K. M.; Caughman, J. B.; Goulding, R. H.; Bonnin, X.

    2012-10-01

    The ORNL helicon experiment has produced large cross section plasmas (12cm) at high densities (up to 4x10^19/m^3 in D and 6x10^19/m^3 in He) at high powers (up to 90kW). The Physics Integration eXperiment (PhIX) will investigate adding electron heating with Whistler waves (18GHz) and EBW (18GHz) to the helicon source plasma in order to increase Te. Interpretative analyses of the helicon discharges in D and He with the SOLPS transport code show that 2D heating profiles based on resonant power absorption calculations reproduce the main features of the measured density and temperature distributions. The PhIX plasma column, including the helicon and RF heated mirror cell, has diameter 12-15 cm and length 3 m. Predictive SOLPS simulations of PhIX, with additional EBW and Whistler power absorption profiles from the GENRAY-C code, indicate a doubling of Te in the mirror cell. With plasma fueling by an upstream gas puff, calculations indicate 2:1 power split between the downstream and upstream targets.

  17. Factor IX gene mutations in haemophilia B: a New Zealand population-based study.

    PubMed

    VAN DE Water, N S; Williams, R; Berry, E W; Ockelford, P A; Browett, P J

    1996-01-01

    Haemophilia B (Christmas disease) is an X-linked bleeding disorder resulting from an inherited deficiency of coagulation factor IX activity. Due to the heterogeneity of mutations within the factor IX gene there is a marked clinical variability in disease severity. By applying techniques of mutational analysis and direct sequencing of PCR products it is now potentially possible to determine the pathogenic gene defect in entire haemophilia B populations. We report here characterization of the factor IX gene defect in all the haemophilia B patients in New Zealand as part of a nationwide approach towards providing efficient and cost-effective haemophilia B genetic counselling services for these families. Twenty-six different mutations were identified in 32 unrelated haemophilia B families. Three defects at nucleotide positions +8,6659 and 17696 are novel mutations which have not been reported by other laboratories. A PCR-based diagnostic screening test for direct mutational analysis could be performed in most cases; 17 of the 26 mutations altered a restriction enzyme recognition sequence and, with the exception of the total gene deletion, base changes not affecting a restriction enzyme site could be detected by allele-specific PCR.

  18. Characterization of a factor IX variant with a glycine207 to glutamic acid mutation.

    PubMed

    Lin, S W; Lin, C N; Hamaguchi, N; Smith, K J; Shen, M C

    1994-09-15

    Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM). This variant contained a glycine (Gly) to glutamic acid (Glu) substitution at the 207th codon of mature factor IX. The functional consequences of the Gly-->Glu mutation in factor IXTaipei9 (IXG207E) were characterized in this study. Plasma-derived IXG207E exhibited a mobility similar to that of normal factor IX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its specific activity was estimated to be 3.5% that of the purified normal factor IX in a one-stage partial thromboplastin time assay (aPTT). Cleavage of factor IXG207E by factor XIa or factor VIIa-tissue factor complex appeared to be normal. When the calcium-dependent conformational change was examined by monitoring quenching of intrinsic fluorescence, both normal factor IX and IXG207E exhibited equivalent intrinsic fluorescence quenching. Activated factor IXG207E (IXaG207E) also binds antithrombin III equally as well as normal factor IXa. However, aberrant binding of the active site probe p-aminobenzamidine was observed for factor XIa-activated factor IXG207E, indicating that the active site pocket of the heavy chain of factor IXaG207E was abnormal. Moreover, the rate of activation of factor X by factor IXaG207E, as measured in a purified system using chromogenic substrates, was estimated to be 1/40 of that of normal factor IXa. A computer-modeled heavy-chain structure of factor IXa predicts a hydrophobic environment surrounding Gly-207 and this Gly forms a hydrogen bound to the active site serine-365. The molecular mechanism of the Gly-->Glu mutation in factor IXTaipei9 might result in the alteration of the microenvironment of the active site pocket which renders the active site serine-365 inaccessible to its substrate. PMID:7915915

  19. Isolation and characterization of a cDNA coding for human factor IX.

    PubMed

    Kurachi, K; Davie, E W

    1982-11-01

    A cDNA library prepared from human liver has been screened for factor IX (Christmas factor), a clotting factor that participates in the middle phase of blood coagulation. The library was screened with a single-stranded DNA prepared from enriched mRNA for baboon factor IX and a synthetic oligonucleotide mixture. A plasmid was identified that contained a cDNA insert of 1,466 base pairs coding for human factor IX. The insert is flanked by G-C tails of 11 and 18 base pairs at the 5' and 3' ends, respectively. It also included 138 base pairs that code for an amino-terminal leader sequence, 1,248 base pairs that code for the mature protein, a stop codon, and 48 base pairs of noncoding sequence at the 3' end. The leader sequence contains 46 amino acid residues, and it is proposed that this sequence includes both a signal sequence and a pro sequence for the mature protein that circulates in plasma. The 1,248 base pairs code for a polypeptide chain composed of 416 amino acids. The amino-terminal region for this protein contains 12 glutamic acid residues that are converted to gamma-carboxyglutamic acid in the mature protein. These glutamic acid residues are coded for by both GAA and GAG. The arginyl peptide bonds that are cleaved in the conversion of human factor IX to factor IXa by factor XIa were identified as Arg145-Ala146 and Arg180-Val181. The cleavage of these two internal peptide bonds results in the formation of an activation peptide (35 amino acids) and factor IXa, a serine protease composed of a light chain (145 amino acids) and a heavy chain (236 amino acids), and these two chains are held together by a disulfide bond(s). The active site residues including histidine, aspartate, and serine are located in the heavy chain at positions 221, 270, and 366, respectively. These amino acids are homologous with His57, Asp102, and Ser195 in the active site of chymotrypsin. Two potential carbohydrate binding sites (Asn-X-Thr) were identified in the activation peptide, and

  20. In vitro mutagenesis study of two critical glutamic acids in the calcium binding loop of the factor IX heavy chain.

    PubMed

    Hamaguchi, N; Stafford, D

    1994-12-01

    We investigated the structural and functional significance of calcium binding in the factor IXa heavy chain by introducing point mutations into the probable calcium binding site (residues 235 and 245). According to factor IXa computer modelling based on trypsin x-ray structure, side chains of two glutamic acid residues, 235 and 245, together with backbone carbonyl groups of residues 237 and 240, bind a calcium ion. Factor IX clotting activity decreased approximately 25 percent on substitution of glutamic acid 235 with lysine. Activity decreased more than 90 percent on substitution of glutamic acid 245 with lysine. Activity also decreased more than 90 percent on substitution of both glutamic acids by lysines. Factor XIa cleavage of factor IXGlu235Lys and factor IXGlu245Lys appeared normal by polyacrylamide gel analysis. (Factor IXGlu235Lys: Factor IX with Lysine substituted for Glutamic acid at residue 235. Factor IXGlu245Lys: Factor IX with Lysine substituted for Glutamic acid at residue 245. Factor IXGlu235&245Lys: Factor IX with Lysine substituted for Glutamic acid at residues 235 and 245.) Activated factor IXGlu235Lys bound the fluorescent active site probe, p-aminobenzamidine, normally, while factor XIa cleaved factor IXGlu245Lys and factor IXGlu235&245Lys failed to bind p-aminobenzamidine. Plasma purified factor IX titrated with terbium showed an increase in luminescence; however, factor IXGlu235Lys and factor IXGlu245Lys had no effect on terbium luminescence. Radioimmunoassays indicate that in calcium's absence, factor IXGlu245Lys adopts a conformation similar to normal factor IX in the presence of calcium. By contrast, factor IXGlu245Lys's conformation in the presence of calcium is similar to that of plasma purified factor IX in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7740454

  1. The serological relationship between Brucella spp., Yersinia enterocolitica serotype IX and Salmonella serotypes of Kauffmann-White group N.

    PubMed Central

    Corbell, M. J.

    1975-01-01

    The serological relationship between Brucella spp., Yersinia enterocolitica IX, and the group N salmonella serotypes S. godesberg, S. landau, S. morehead, S. neusdorf, S. soerenga and S. urbana was examined using agglutination, antiglobulin, complement fixation, immunodiffusion and fluorescent antibody methods. Antisera to the group N salmonella serotypes all reacted to significant titres in agglutination and complement fixation, but not antiglobulin or immunodiffusion tests with smooth brucella antigens. These antisera also reacted in agglutination, but not antiglobulin, tests with Y. enterocolitica IX. They did not react significantly in any tests with rough brucella antigens. Conversely, antisera to smooth Brucella spp. agglutinated group N salmonellas to low titre and Y. enterocolitica IX to titres similar to those given against the homologous strain. Antiserum to Y. enterocolitica IX on the other hand reacted with smooth brucella antigens to high titre in agglutination, complement fixation and antiglobulin tests, and with the group N salmonella antigens to substantial titres in agglutination tests. In direct fluorescent antibody tests, smooth Brucella strains and Y. enterocolitica IX reacted strongly with FITC-labelled antibody to Br. abortus whereas the group N salmonella strains reacted weakly. In tests with monospecific antisera to the A and M determinants of Br. abortus and Br. melitensis respectively, Y. enterocolitica IX reacted only with the antiserum to the A determinant whereas group N salmonellas reacted to low titre with both A and M antisera. The results of cross-absorption tests confirmed this relationship and suggested that the O30 antigens of group N salmonella serotypes contained antigenic determinants similar to, but not identical with, the antigenic structure shared by smooth Brucella spp. and Y. enterocolitica IX. PMID:807618

  2. 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.

  3. The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy.

    PubMed

    Tyrrell, J; Campbell, S M; Curnow, A

    2011-04-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized to successfully treat licensed indications (e.g. actinic keratosis (AK), superficial basal cell carcinoma (sBCC) and Bowen's disease (BD)) in the UK. Air cooling devices (ACD) are commonly utilized as a method of pain relief, however the effect of this on treatment outcome has never been extensively investigated. This non-randomized, retrospective observational controlled study investigated whether the application of the ACD limited photosensitiser (protoporphyrin IX - PpIX) photobleaching during irradiation and/or subsequent clinical outcome. Patients utilizing the ACD throughout treatment were observed to undergo significantly less PpIX photobleaching than the control group (P<0.001) and complete clinical clearances observed at 3 months were also reduced within the ACD group. Separate analysis of the different lesion types indicated that significantly less photobleaching occurred in AK lesions with ACD and all lesion types failed to fully utilize the accumulated PpIX when ACD was employed. The application of the ACD as pain relief during light irradiation therefore resulted in lower PpIX photobleaching which corresponded to a reduction in the efficacy of PDT treatment. Whilst the ACD is an effective method of dermatological PDT analgesia it should be utilized as sparingly as possible to minimize any deleterious effects on treatment outcome.

  4. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

    PubMed

    Sancey, Lucie; Kotb, Shady; Truillet, Charles; Appaix, Florence; Marais, Arthur; Thomas, Eloïse; van der Sanden, Boudewijn; Klein, Jean-Philippe; Laurent, Blandine; Cottier, Michèle; Antoine, Rodolphe; Dugourd, Philippe; Panczer, Gérard; Lux, François; Perriat, Pascal; Motto-Ros, Vincent; Tillement, Olivier

    2015-03-24

    We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.

  5. Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms

    PubMed Central

    Simko, Veronika; Takacova, Martina; Debreova, Michaela; Laposova, Katarina; Ondriskova-Panisova, Elena; Pastorekova, Silvia; Csaderova, Lucia; Pastorek, Jaromir

    2016-01-01

    Dexamethasone is a synthetic glucocorticoid frequently used to suppress side-effects of anticancer chemotherapy. In the present study, we showed that dexamethasone treatment leads to concentration-dependent downregulation of cancer-associated marker, carbonic anhydrase IX (CA IX), at the level of promoter activity, mRNA and protein expression in 2D and 3D cancer cell models. The effect of dexamethasone on CA IX expression under hypoxic conditions is predominantly mediated by impaired transcriptional activity and decreased protein level of the main hypoxic transcription factor HIF-1α. In addition, CA9 downregulation can be caused by protein-protein interactions between activated glucocorticoid receptors, major effectors of glucocorticoid action, and transcription factors that trigger CA9 transcription (e.g. AP-1). Moreover, we identified a potential NF-κB binding site in the CA9 promoter and propose the involvement of NF-κB in the dexamethasone-mediated inhibition of CA9 transcription. As high level of CA IX is often linked to aggressive tumor behavior, poor prognosis and chemo- and radiotherapy resistance, uncovering its reduction after dexa-methasone treatment and implication of additional regulatory mechanisms can be relevant for the CA IX-related clinical applications. PMID:27431580

  6. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

    PubMed

    Sancey, Lucie; Kotb, Shady; Truillet, Charles; Appaix, Florence; Marais, Arthur; Thomas, Eloïse; van der Sanden, Boudewijn; Klein, Jean-Philippe; Laurent, Blandine; Cottier, Michèle; Antoine, Rodolphe; Dugourd, Philippe; Panczer, Gérard; Lux, François; Perriat, Pascal; Motto-Ros, Vincent; Tillement, Olivier

    2015-03-24

    We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs. PMID:25703068

  7. 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.

  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. 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.

  10. Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves.

    PubMed

    Wahyuni, Tutik Sri; Widyawaruyanti, Aty; Lusida, Maria Inge; Fuad, Achmad; Soetjipto; Fuchino, Hiroyuki; Kawahara, Nobuo; Hayashi, Yoshitake; Aoki, Chie; Hotta, Hak

    2014-12-01

    Hepatitis C virus (HCV) infection is highly prevalent among global populations, with an estimated number of infected patients being 170 million. Approximately 70-80% of patients acutely infected with HCV will progress to chronic liver disease, such as liver cirrhosis and hepatocellular carcinoma, which is a substantial cause of morbidity and mortality worldwide. New therapies for HCV infection have been developed, however, the therapeutic efficacies still need to be improved. Medicinal plants are promising sources for antivirals against HCV. A variety of plants have been tested and proven to be beneficial as antiviral drug candidates against HCV. In this study, we examined extracts, their subfractions and isolated compounds of Ruta angustifolia leaves for antiviral activities against HCV in cell culture. We isolated six compounds, chalepin, scopoletin, γ-fagarine, arborinine, kokusaginine and pseudane IX. Among them, chalepin and pseudane IX showed strong anti-HCV activities with 50% inhibitory concentration (IC₅₀) of 1.7 ± 0.5 and 1.4 ± 0.2 μg/ml, respectively, without apparent cytotoxicity. Their anti-HCV activities were stronger than that of ribavirin (2.8 ± 0.4 μg/ml), which has been widely used for the treatment of HCV infection. Mode-of-action analyses revealed that chalepin and pseudane IX inhibited HCV at the post-entry step and decreased the levels of HCV RNA replication and viral protein synthesis. We also observed that arborinine, kokusaginine and γ-fagarine possessed moderate levels of anti-HCV activities with IC₅₀ values being 6.4 ± 0.7, 6.4 ± 1.6 and 20.4 ± 0.4 μg/ml, respectively, whereas scopoletin did not exert significant anti-HCV activities at 30 μg/ml.

  11. Observations of the bright novalike variable IX Velorum with the Hopkins Ultraviolet Telescope

    NASA Technical Reports Server (NTRS)

    Long, Knox S.; Wade, Richard A.; Blair, William P.; Davidsen, Arthur F.; Hubeny, Ivan

    1994-01-01

    The Hopkins Ultraviolet Telescope, an experiment flown on the Space Shuttle as part of the Astro-1 mission, was used to obtain a spectrum of the novalike variable IX Vel (= CPD -48 deg 1577) in the wavelength range 830-1860 A. The observation revealed a rich absorption-line and continuum spectrum that peaks near 1050 A at a flux of 1.6 x 10(exp -11) ergs/sq cm/s/A. In the sub-Lyman-alpha region, some of the more prominent absorption lines are S VI lambda lambda-933, 945, C III lambda-977, Lyman-beta, O VI lambda lambda-1032, 1038, P V lambda lambda-1118, 1128, and C III lambda-1176. No emission was detected below the Lyman limit. The overall continuum shape of IX Vel in the FUV can be approximated using models of an optically thick accretion disk in which the integrated spectrum has been constructed by summing model stellar atmospheres or proper disk model spectra. However, if the distance to IX Vel is approximately 95 pc, standard disk models without reddening cannot simultaneously reproduce the color and flux in the UV. While interstellar reddening can reconcile this difference, the amount of reddening appears inconsistent with the absence of a 2200 A bump in the spectrum and the very low H I column density measured along the line of sight. Improved fits to the data can be obtained by modifying the accretion disk stucture within three white dwarf radii. None of the models reproduces the profiles of the Li- and Na-like ions, which are observed as strong but relatively narrow absorption lines, and which are almost surely due to a wind above the disk.

  12. Wavelengths and levels of the Na I isoelectronic sequence from K IX through Mn XV

    NASA Technical Reports Server (NTRS)

    Cohen, L.; Behring, W. E.

    1976-01-01

    The seven spectra K IX through Mn XV have been analyzed and the series limits determined. We present the adopted wavelengths and the derived energy levels and term splittings. The highly ionized atoms were produced in a spark source and recorded mainly on a 3 m grazing incidence spectrograph. Many new lines have been identified and many previously given wavelengths have been revised. All wavelengths have been examined for consistency by least-squares-fitting procedures and other tests. These procedures indicated misidentified lines and incorrect wavelengths which we corrected when possible. A discussion of the errors is given.

  13. NASA Aerosciences Perspective on Proposed De-Scope of Ares I-X Development Flight Instrumentation

    NASA Technical Reports Server (NTRS)

    Schuster, David M.

    2009-01-01

    This position paper is written as a result of a number of emails and a presentation that have recently been circulated concerning the potential reduction of Development Flight Instrumentation (DFI) to be included on the Ares I-X flight test vehicle. A reduction in instrumentation has been proposed presumably to reduce project costs and relieve project schedule pressures. This proposal has generated a significant amount of discussion on both sides of the issue, primarily from those within the project. The intention here is to provide a perspective on this issue from outside the mainline project.

  14. How far can we go? Quantum-chemical investigations of oxidation state +IX.

    PubMed

    Himmel, Daniel; Knapp, Carsten; Patzschke, Michael; Riedel, Sebastian

    2010-03-15

    The highest known oxidation state of any element is +VIII. After the recent discovery of Ir(VIII)O(4) under cryogenic conditions, we have investigated the stability of cationic species [MO(4)](+) (M=Rh,Ir,Mt). Such compounds would formally represent the new oxidation state +IX, which is experimentally unknown so far for the whole periodic table. [IrO(4)](+) is predicted to be the most promising candidate. The calculated spin-orbit (SO) coupling shows only minor effects on the stability of the iridium species, whereas SO-coupling increases enormously for the corresponding Eka-Iridium (Meitnerium) complexes and destabilizes these.

  15. How far can we go? Quantum-chemical investigations of oxidation state +IX.

    PubMed

    Himmel, Daniel; Knapp, Carsten; Patzschke, Michael; Riedel, Sebastian

    2010-03-15

    The highest known oxidation state of any element is +VIII. After the recent discovery of Ir(VIII)O(4) under cryogenic conditions, we have investigated the stability of cationic species [MO(4)](+) (M=Rh,Ir,Mt). Such compounds would formally represent the new oxidation state +IX, which is experimentally unknown so far for the whole periodic table. [IrO(4)](+) is predicted to be the most promising candidate. The calculated spin-orbit (SO) coupling shows only minor effects on the stability of the iridium species, whereas SO-coupling increases enormously for the corresponding Eka-Iridium (Meitnerium) complexes and destabilizes these. PMID:20127784

  16. Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds.

    PubMed

    Durdagi, Serdar; Korkmaz, Neslihan; Işık, Semra; Vullo, Daniela; Astley, Demet; Ekinci, Deniz; Salmas, Ramin E; Senturk, Murat; Supuran, Claudiu T

    2016-12-01

    A series of hydroxylic compounds (1-10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068-4003, 0.012-9.9 and 0.025-115 μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the KI values were calculated.

  17. 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.

  18. Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds.

    PubMed

    Durdagi, Serdar; Korkmaz, Neslihan; Işık, Semra; Vullo, Daniela; Astley, Demet; Ekinci, Deniz; Salmas, Ramin E; Senturk, Murat; Supuran, Claudiu T

    2016-12-01

    A series of hydroxylic compounds (1-10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068-4003, 0.012-9.9 and 0.025-115 μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the KI values were calculated. PMID:26634620

  19. Nonacog gamma, a novel recombinant factor IX with low factor IXa content for treatment and prophylaxis of bleeding episodes.

    PubMed

    Turecek, Peter L; Abbühl, Brigitt; Tangada, Srilatha D; Chapman, Miranda; Gritsch, Herbert; Rottensteiner, Hanspeter; Schrenk, Gerald; Mitterer, Artur; Dietrich, Barbara; Höllriegl, Werner; Schiviz, Alexandra; Horling, Frank; Reipert, Birgit M; Muchitsch, Eva-Maria; Pavlova, Borislava G; Scheiflinger, Friedrich

    2015-03-01

    Nonacog gamma is a new recombinant factor IX to treat factor IX deficiency. It is indicated for control of bleeding episodes, perioperative management and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia B. Nonacog gamma was first approved in the USA in June 2013 under the trade name RIXUBIS followed by market approvals in Australia and the EU in 2014, and marketing authorization decision is pending in Japan. Nonacog gamma is derived from a recombinant Chinese hamster ovary cell line using a state of the art biotechnological manufacturing process. Recombinant factor IX is produced by Baxter's protein-free fermentation technology, which was first developed for ADVATE. The product is purified and formulated in the absence of any human or animal-derived protein. Nonacog gamma was characterized both in comprehensive in vitro and in vivo non-clinical studies as well as in an extensive clinical trial program. PMID:25660348

  20. Ares I-X First Flight Loss of Vehicle Probability Analysis

    NASA Technical Reports Server (NTRS)

    Bigler, Mark A.; Cross, Robert B.; Osborn, John H.; Li, Yunnhon

    2011-01-01

    As part of the Constellation (Cx) Program development effort, several test flights were planned to prove concepts and operational capabilities of the new vehicles being developed. The first test, involving the Eastern Test Range, is the Ares I-X launched in 2009. As part of this test, the risk to the general public was addressed to ensure it is within Air Force requirements. This paper describes the methodology used to develop first flight estimates of overall loss of vehicle (LOV) failure probability, specifically for the Ares I-X. The method described in this report starts with the Air Force s generic failure probability estimate for first flight and adjusts the value based on the complexity of the vehicle as compared to the complexity of a generic vehicle. The results estimate a 1 in 9 probability of failure. The paper also describes traditional PRA methods used in this assessment, which were then combined with the updated first flight risk methodology to generate inputs required by the malfunction turn analysis to support estimate of casualty (Ec) calculations as part of the Final Flight Data Package (FFDP) delivered to the Eastern Range for Final Flight Plan Approval.

  1. N-Methyl Mesoporphyrin IX Inhibits Phycocyanin, but Not Chlorophyll Synthesis in Cyanidium caldarium1

    PubMed Central

    Beale, Samuel I.; Chen, Nancy C.

    1983-01-01

    The ability of N-methyl mesoporphyrin IX (NMMP) to block heme synthesis by specifically inhibiting enzymic iron insertion into protoporphyrin IX was exploited to test whether heme is a precursor of the bilin chromophore of phycocyanin (PC). A strain of the unicellular rhodophyte Cyanidium caldarium which forms normal amounts of both chlorophyll (Chl) and PC in the dark was employed to avoid phototoxic effects of exogenous porphyrins. Relative Chl and PC content were assayed spectrophotometrically on whole cell suspensions. When cells were grown in the dark on a glucose-based heterotrophic medium at 42°C, neither division rate nor Chl synthesis was affected by NMMP up to 3.0 micromolar and for as long as 72 hours. NMMP had a dose-dependent inhibitory effect on PC synthesis. PC to Chl absorbance ratios, relative to control cell values, were 100%, 89%, 86%, and 50% in cells grown for 48 hours with 0.3, 1.0, 3.0, and 10.0 micromolar NMMP, respectively. NMMP also caused the accumulation of intracellular protoporphyrin. The ability of NMMP to cause intracellular accumulation of protoporphyrin and to block PC synthesis specifically while allowing normal Chl formation is consistent with its action as a specific inhibitor of enzymic iron chelation, and supports the role of heme as a precursor to the phycobilins. PMID:16662815

  2. Targeting of the epidermal growth factor receptor with mesoporphyrin IX-peptide conjugates

    PubMed Central

    Fontenot, Krystal R.; Ongarora, Benson G.; LeBlanc, Logan E.; Zhou, Zehua; Jois, Seetharama D.; Vicente, M. Graça H.

    2016-01-01

    The synthesis and in vitro evaluation of four mesoporphyrin IX-peptide conjugates designed to target EGFR, over-expressed in colorectal and other cancers, are reported. Two peptides with known affinity for EGFR, LARLLT (1) and GYHWYGYTPQNVI (2), were conjugated to mesoporphyrin IX (MPIX, 3) via one or both the propionic side chains, directly (4, 5) or with a triethylene glycol spacer (7, 8). The conjugates were characterized using NMR, MS, CD, SPR, UV-vis and fluorescence spectroscopies. Energy minimization and molecular dynamics suggest different conformations for the conjugates. SPR studies show that conjugate 4, bearing two LARLLT with no PEG spacers, has the greatest affinity for binding to EGFR, followed by conjugate 7 with two PEG and two LARLLT sequences. Molecular modeling and docking studies suggest that both conjugates 4 and 7 can bind to monomer and dimer EGFR in open and closed conformations. The cytotoxicity and cellular targeting ability of the conjugates were investigated in human HEp2 cells over-expressing EGFR. All conjugates showed low dark- and photo-toxicities. The cellular uptake was highest for conjugates 4 and 8 and lowest for 7 bearing two LARLLT linked via PEG groups, likely due to decreased hydrophobicity. Among the conjugates investigated 4 is the most efficient EGFR-targeting agent, and therefore the most promising for the detection of cancers that over-express EGFR. PMID:27738394

  3. 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

  4. No Evidence for Protoplanetary Disk Destruction By OBS Stars in the MYStIX Sample

    NASA Astrophysics Data System (ADS)

    Richert, Alexander J. W.; Feigelson, Eric D.; Getman, Konstantin V.; Kuhn, Michael A.

    2015-09-01

    Hubble Space Telescope images of proplyds in the Orion Nebula, as well as submillimeter/radio measurements, show that the dominant O7 star {θ }1Ori C photoevaporates nearby disks around pre-main-sequence stars. Theory predicts that massive stars photoevaporate disks within distances of the order of 0.1 pc. These findings suggest that young, OB-dominated massive H ii regions are inhospitable to the survival of protoplanetary disks and, subsequently, to the formation and evolution of planets. In the current work, we test this hypothesis using large samples of pre-main-sequence stars in 20 massive star-forming regions selected with X-ray and infrared photometry in the MYStIX survey. Complete disk destruction would lead to a deficit of cluster members with an excess in JHKS and Spitzer/IRAC bands in the vicinity of O stars. In four MYStIX regions containing O stars and a sufficient surface density of disk-bearing sources to reliably test for spatial avoidance, we find no evidence for the depletion of inner disks around pre-main-sequence stars in the vicinity of O-type stars, even very luminous O2-O5 stars. These results suggest that massive star-forming regions are not very hostile to the survival of protoplanetary disks and, presumably, to the formation of planets.

  5. The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis

    PubMed Central

    2014-01-01

    Background In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to adapt to modern vaccine production. Therefore, we derived previously a continuous suspension cell line, AGE1.CR.pIX, from muscovy duck and established chemically-defined media for virus propagation. Results To better understand vaccine production processes, we developed a stoichiometric model of the central metabolism of AGE1.CR.pIX cells and applied flux variability and metabolic flux analysis. Results were compared to literature dealing with mammalian and insect cell culture metabolism focusing on the question whether cultured avian cells differ in metabolism. Qualitatively, the observed flux distribution of this avian cell line was similar to distributions found for mammalian cell lines (e.g. CHO, MDCK cells). In particular, glucose was catabolized inefficiently and glycolysis and TCA cycle seem to be only weakly connected. Conclusions A distinguishing feature of the avian cell line is that glutaminolysis plays only a minor role in energy generation and production of precursors, resulting in low extracellular ammonia concentrations. This metabolic flux study is the first for a continuous avian cell line. It provides a basis for further metabolic analyses to exploit the biotechnological potential of avian and vertebrate cell lines and to develop specific optimized cell culture processes, e.g. vaccine production processes. PMID:25077436

  6. 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.

  7. Homoclinic chaos in axisymmetric Bianchi-IX cosmological models with an ad hoc quantum potential

    SciTech Connect

    Correa, G. C.; Stuchi, T. J.; Joras, S. E.

    2010-04-15

    In this work we study the dynamics of the axisymmetric Bianchi-IX cosmological model with a term of quantum potential added. As it is well known, this class of Bianchi-IX models is homogeneous and anisotropic with two scale factors, A(t) and B(t), derived from the solution of Einstein's equation for general relativity. The model we use in this work has a cosmological constant and the matter content is dust. To this model we add a quantum-inspired potential that is intended to represent short-range effects due to the general relativistic behavior of matter in small scales and play the role of a repulsive force near the singularity. We find that this potential restricts the dynamics of the model to positive values of A(t) and B(t) and alters some qualitative and quantitative characteristics of the dynamics studied previously by several authors. We make a complete analysis of the phase space of the model finding critical points, periodic orbits, stable/unstable manifolds using numerical techniques such as Poincare section, numerical continuation of orbits, and numerical globalization of invariant manifolds. We compare the classical and the quantum models. Our main result is the existence of homoclinic crossings of the stable and unstable manifolds in the physically meaningful region of the phase space [where both A(t) and B(t) are positive], indicating chaotic escape to inflation and bouncing near the singularity.

  8. Spitzer IRAC Observations of IR Excess in Holmberg IX X-1: A Circumbinary Disk or a Variable Jet?

    NASA Astrophysics Data System (ADS)

    Dudik, R. P.; Berghea, C. T.; Roberts, T. P.; Grisé, F.; Singh, A.; Pagano, R.; Winter, L. M.

    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 variable jet.

  9. In Vitro Comparison of Hypericin and 5-Aminolevulinic Acid-Derived Protoporphyrin IX for Photodynamic Inactivation of Medulloblastoma Cells

    PubMed Central

    Ritz, Rainer; Scheidle, Christian; Noell, Susan; Roser, Florian; Schenk, Martin; Dietz, Klaus; Strauss, Wolfgang S. L.

    2012-01-01

    Background Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX). Methods In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells. Results All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation with HYP up to 10 µM resulted in a rapid increase in fluorescence intensity, which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The [lethal dose (light dose that is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm2 in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 µM after an incubation time of 2 h and an illumination wavelength of 595 nm. The value was 0.47 J/cm2. Conclusion By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower . Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas. PMID:23251668

  10. A highly selective space-folded photo-induced electron transfer fluorescent probe for carbonic anhydrase isozymes IX and its applications for biological imaging.

    PubMed

    Zhang, Shenyi; Yang, Chunmei; Lu, Weiqiang; Huang, Jin; Zhu, Weiping; Li, Honglin; Xu, Yufang; Qian, Xuhong

    2011-08-01

    The first highly selective and sensitive fluorescent probe Z1 for detection of carbonic anhydrase IX (CA IX) over isoforms CA I and CA II was developed. As demonstrated, Z1 worked effectively in both enzymatic systems and living hypoxia cells.

  11. Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

    NASA Astrophysics Data System (ADS)

    Warren, Christine B.; Lohser, Sara; Wene, Lauren C.; Pogue, Brian W.; Bailin, Philip L.; Maytin, Edward V.

    2010-09-01

    Topical 5-aminolevulinic acid (ALA) is widely used in photodynamic therapy (PDT) of actinic keratoses (AK), a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX (PpIX) accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements (5 replicates) were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin.

  12. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy.

    PubMed

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 10(6) M(-1)). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  13. 77 FR 29633 - Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... and Alta IX to interconnect the full planned capacity of Petitioners' wind and solar generation... Energy Regulatory Commission Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC, Alta Wind XIII, LLC, Alta Wind XIV, LLC, Alta Wind XV, LLC, Alta...

  14. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-05-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M‑1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.

  15. Expanding Girls' Occupational Potential: A Case Study of the Implementation of Title IX's Anti-Sex Segregation Provision in Seventh Grade Practical Arts.

    ERIC Educational Resources Information Center

    Wirtenberg, Jeana

    Title IX has significant implications for overcoming generations of inequality in the educational opportunities that have been afforded to females. The sex-desegregation of industrial arts and home economics was examined to measure the impact of Title IX on the occupational potential of seventh-grade girls and boys. In the experimental condition,…

  16. Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using Structure-Activity Relationships of Glucosyl-Based Sulfamates.

    PubMed

    Mahon, Brian P; Lomelino, Carrie L; Ladwig, Janina; Rankin, Gregory M; Driscoll, Jenna M; Salguero, Antonieta L; Pinard, Melissa A; Vullo, Daniela; Supuran, Claudiu T; Poulsen, Sally-Ann; McKenna, Robert

    2015-08-27

    Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 Å or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically "map" key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors. PMID:26203869

  17. Pp IX silica nanoparticles demonstrate differential interactions with in vitro tumor cell lines and in vivo mouse models of human cancers.

    PubMed

    Simon, Virginie; Devaux, Corinne; Darmon, Audrey; Donnet, Thibault; Thiénot, Edouard; Germain, Matthieu; Honnorat, Jérôme; Duval, Alex; Pottier, Agnès; Borghi, Elsa; Levy, Laurent; Marill, Julie

    2010-01-01

    Protoporphyrin IX (Pp IX) silica nanoparticles, developed for effective use in photodynamic therapy (PDT), were explored in in vitro and in vivo models with the ambition to improve knowledge on the role of biological factors in the photodamage. Pp IX silica nanoparticles are found efficient at temperature with extreme metabolic downregulation, which suggest a high proportion of passive internalization. For the first time, clearance of silica nanoparticles on tumor cells is established. Cell viability assessment in six tumor cell lines is reported. In all tumor types, Pp IX silica nanoparticles are more efficient than free Pp IX. A strong fluorescence signal of reactive oxygen species generation colocalized with Pp IX silica nanoparticles, correlates with 100% of cell death. In vivo studies performed in HCT 116, A549 and glioblastoma multiforme tumors-bearing mice show tumor uptake of Pp IX silica nanoparticles with better tumor accumulation than the control alone, highlighting a high selectivity for tumor tissues. As observed in in vitro tests, tumor cell type is likely a major determinant but tumor microenvironment could more influence this differential time accumulation dynamic. The present results strongly suggest that Pp IX silica nanoparticles may be involved in new alternative local applications of PDT. PMID:19769577

  18. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    PubMed Central

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M−1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  19. VizieR Online Data Catalog: Collision strengths in FeIX (Tayal+, 2015)

    NASA Astrophysics Data System (ADS)

    Tayal, S. S.; Zatsarinny, O.

    2016-02-01

    Collision strengths and thermally averaged collision strengths for a large number of extreme-ultraviolet lines of FeIX arising by electron impact have been reported. The thermally averaged collision strengths are calculated at electron temperatures in the range 104-107K for the 122043 forbidden and allowed transitions between the 370 fine-structure levels. The atomic parameters for FeIX play an important role in modeling of various astrophysical plasmas, including especially the solar corona. The B-spline Breit-Pauli R-matrix method has been used in the calculation of collision strengths. The target wave functions and transition probabilities have been determined by combining the multiconfiguration Hartree-Fock method with the B-spline box-based multichannel expansions. We have included 370 fine-structure levels of FeIX in the energy region up to 3s23p55s states. The close-coupling expansion includes levels of the 3s23p6, 3s23p53d, 4l, 5s, 3s3p63d, 4s, 4p, 3s23p43d2, 3s3p53d2 configurations and some low-lying levels of the 3s23p33d3 configuration in our collision strengths and transition probabilities calculations. There is a good agreement with the previous R-matrix collision strength calculations by Storey et al. (2002, J/A+A/394/753) and Del Zanna et al. (2014, J/A+A/565/A77) for transitions between the lowest 17 levels of the 3s23p6, 3s23p53d and 3s3p63d configurations, especially for electron temperatures logT(K)>=5.0. The transitions between the first 17 levels are dominated by Rydberg series of resonances converging to the levels of the 3s23p43d2 configuration. The present results and the calculation of Del Zanna et al. show significant differences for many weaker forbidden and intercombination transitions with thermally averaged collision strengths smaller than 0.01. (3 data files).

  20. Thermally Averaged Collision Strengths for Extreme-ultraviolet Line of Fe IX

    NASA Astrophysics Data System (ADS)

    Tayal, S. S.; Zatsarinny, O.

    2015-10-01

    Collision strengths and thermally averaged collision strengths for a large number of extreme-ultraviolet lines of Fe ix arising by electron impact have been reported. The thermally averaged collision strengths are calculated at electron temperatures in the range 104-107 K for the 122,043 forbidden and allowed transitions between the 370 fine-structure levels. The atomic parameters for Fe ix play an important role in modeling of various astrophysical plasmas, including especially the solar corona. The B-spline Breit-Pauli R-matrix method has been used in the calculation of collision strengths. The target wave functions and transition probabilities have been determined by combining the multiconfiguration Hartree-Fock method with the B-spline box-based multichannel expansions. We have included 370 fine-structure levels of Fe ix in the energy region up to 3{s}23{p}55s states. The close-coupling expansion includes levels of the 3{s}23{p}6, 3{s}23{p}53d,4l,5s, 3s3{p}63d,4s,4p, 3{s}23{p}43{d}2, 3s3{p}53{d}2 configurations and some low-lying levels of the 3{s}23{p}33{d}3 configuration in our collision strengths and transition probabilities calculations. There is a good agreement with the previous R-matrix collision strength calculations by Storey et al. and Del Zanna et al. for transitions between the lowest 17 levels of the 3{s}23{p}6, 3{s}23{p}53d, and 3s3{p}63d configurations, especially for electron temperatures log T(K) ≥ 5.0. The transitions between the first 17 levels are dominated by Rydberg series of resonances converging to the levels of the 3{s}23{p}43{d}2 configuration. The present results and the calculation of Del Zanna et al. show significant differences for many weaker forbidden and intercombination transitions with thermally averaged collision strengths smaller than 0.01.

  1. A pilot study comparing the pain sensations during PpIX build-up and clearance phases

    NASA Astrophysics Data System (ADS)

    Mikolajewska, P.; Juzeniene, A.; Iani, V.; Sollund, H.; Norsang, G.; Moan, J.

    2009-06-01

    It has been speculated that topical application of 5-aminolevulinic acid (ALA) or methyl 5-aminolevulinate (MAL) may be more painful during light exposure after longer application times of the compounds than after shorter times, even though the same levels of protoporphyrin IX (PpIX) is produced in both cases. The aim of our study was to investigate pain induction in the build-up and clearance phases of PpIX in the skin of healthy volunteers. 0.6 mmol/g of ALA (10% wt/wt) and MAL (11% wt/wt) creams were applied on the volunteers. The creams were maintained on the spots for 20- 24 hours and then wiped off. Subsequently, fresh creams were applied on the other arm of the volunteers for 4- 6 hours. Fluorescence emission spectra for all spots were measured every hour until the fluorescence levels were similar in both arms for ALA and MAL. Then the test areas were exposed to light until pain occurred. Time for pain to occur was recorded. The fluorescence of PpIX was measured before and after light exposure. PDT in the clearance phase seems to induce pain faster than in the build-up phase for ALA and MAL. Due to large interpersonal variations between volunteers further investigation is needed.

  2. Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting

    SciTech Connect

    Campos, Samuel K.; Barry, Michael A. . E-mail: mab@bcm.edu

    2006-06-05

    The direct genetic modification of adenoviral capsid proteins with new ligands is an attractive means to confer targeted tropism to adenoviral vectors. Although several capsid proteins have been reported to tolerate the genetic fusion of foreign peptides and proteins, direct comparison of cell targeting efficiencies through the different capsomeres has been lacking. Likewise, direct comparison of with one or multiple ligands has not been performed due to a lack of capsid-compatible ligands available for retargeting. Here we utilize a panel of metabolically biotinylated Ad vectors to directly compare targeted transduction through the fiber, protein IX, and hexon capsomeres using a variety of biotinylated ligands including antibodies, transferrin, EGF, and cholera toxin B. These results clearly demonstrate that cell targeting with a variety of high affinity receptor-binding ligands is only effective when transduction is redirected through the fiber protein. In contrast, protein IX and hexon-mediated targeting by the same set of ligands failed to mediate robust vector targeting, perhaps due to aberrant trafficking at the cell surface or inside targeted cells. These data suggest that vector targeting by genetic incorporation of high affinity ligands will likely be most efficient through modification of the adenovirus fiber rather than the protein IX and hexon capsomeres. In contrast, single-step monomeric avidin affinity purification of Ad vectors using the metabolic biotinylation system is most effective through capsomeres like protein IX and hexon.

  3. Beyond the Classroom: Using Title IX to Measure the Return to High School Sports. NBER Working Paper No. 15728

    ERIC Educational Resources Information Center

    Stevenson, Betsey

    2010-01-01

    Between 1972 and 1978 U.S. high schools rapidly increased their female athletic participation rates--to approximately the same level as their male athletic participation rates--in order to comply with Title IX, a policy change that provides a unique quasi-experiment in female athletic participation. This paper examines the causal implications of…

  4. Agora IX: Alternative Education and Training Processes (Thessaloniki, Greece, June 26-27, 2000). CEDEFOP Panorama Series.

    ERIC Educational Resources Information Center

    European Centre for the Development of Vocational Training, Thessaloniki (Greece).

    This document contains the agenda and papers presented at the Agora IX meeting in Thessaloniki, Greece in June 2000 on alternative education and training processes. The papers are "Integration of Migrant Pupils in the Danish Education System" (Bang); "Support Services for Inclusive Education" (De Vroey); "Single Sex Schooling or Coeducation?"…

  5. A Quest for Equality: Title IX, The Second Year. Proceedings (Indiana University, Indiana, January 19-20, 1977).

    ERIC Educational Resources Information Center

    Aquila, Frank D., Ed.; Hummel, Judy, Ed.

    The papers presented in this volume are the result of a conference designed to assist school personnel in understanding and developing plans to eradicate sex discrimination in schools. The works included are: "The Subtleties of Sexism: A Short, Short Story," by Sharon B. Lord; "Legal Ramifications and Concepts of Title IX," by Charles E. Guerrier…

  6. "Prompt and Equitable" Explained: How to Craft a Title IX Compliant Sexual Harassment Policy and Why It Matters

    ERIC Educational Resources Information Center

    Block, Jason A.

    2012-01-01

    An April 2011 "Dear Colleague" letter issued by the U.S. Department of Education's Office for Civil Rights provided new guidance related to Title IX and the civil rights violation inherent in sexual harassment cases. Using the "Dear Colleague" letter as a guide, this article will provide best practice suggestions to remedy gender discrimination…

  7. Flavobacterium columnare type IX secretion system mutations result in defects in gliding motility and loss of virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gliding bacterium Flavobacterium columnare causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. The related bacterium Flavobacterium johnsoniae uses a type IX secretion system (T9SS) to secrete enzymes, adhesin...

  8. Egg-Citing! Isolation of Protoporphyrin IX from Brown Eggshells and Its Detection by Optical Spectroscopy and Chemiluminescence

    ERIC Educational Resources Information Center

    Dean, Michelle L.; Miller, Tyson A.; Bruckner, Christian

    2011-01-01

    A simple and cost-effective laboratory experiment is described that extracts protoporphyrin IX from brown eggshells. The porphyrin is characterized by UV-vis and fluorescence spectroscopy. A chemiluminescence reaction (peroxyoxalate ester fragmentation) is performed that emits light in the UV region. When the porphyrin extract is added as a fluor…

  9. Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.

    PubMed

    Crossley, M; Brownlee, G G

    1990-05-31

    Haemophilia B (or Christmas disease) is an inherited, X-linked bleeding disorder caused by mutations in the gene for clotting factor IX. There is a rare class of patients, exemplified by haemophilia B Leyden, who suffer from haemophilia B as children but improve after puberty. In these patients, plasma factor IX concentrations are less than 10% of normal during childhood, but after puberty they gradually rise to between 40 and 80% of normal. Mutations clustered around the main transcription start point (defined as +1 (ref.2)) have been reported in seven of these patients (at -20 (refs 1, 3, 4); -6 (refs 5, 6) and +13 (refs 7, 8)). To determine how these mutations interfere with factor IX expression, we have assayed for transcription factors binding to this area and have identified a nuclear factor-1 liver (NF1-L) binding site (-99 to -76) and a binding site for the CCAAT/enhancer binding protein (C/EBP) (+1 to +18). We show that the A----G mutation at +13 prevents the binding of C/EBP to this site. Furthermore, we show that C/EBP is capable of transactivating a cotransfected normal factor IX promoter but not the mutant promoter. This is the first natural mutation to be reported which disrupts a C/EBP binding site and is an illustration of the importance of this transcription factor in humans.

  10. Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene.

    PubMed

    Rees, D J; Rizza, C R; Brownlee, G G

    Haemophilia B (Christmas disease) is an inherited, recessive, sex-linked, haemorrhagic condition caused by a defect in the intrinsic clotting factor IX. This disease occurs in males at a frequency of approximately 1 in 30,000. Patients differ in the severity of their clinical symptoms, and variation in the clotting activity and in the concentration of factor IX antigen in their plasma has been demonstrated. There is probably heterogeneity in the molecular defects of the factor IX gene causing the disease. Here we study a severely affected, antigen-negative patient, and show that the only significant sequence difference from the normal factor IX gene is a point mutation changing the obligatory GT to a TT within the donor splice junction of exon f. We infer that this change is the cause of the disease in this individual. In addition, we have used oligodeoxynucleotide probes specific for this mutation to demonstrate the feasibility of carrier detection and prenatal diagnosis for relatives of the patient.

  11. Modeling of Iron K Lines: Radiative and Auger Decay Data for Fe II-Fe IX

    NASA Technical Reports Server (NTRS)

    Palmeri, P.; Mendoza, C.; Kallman, T. R.; Bautista, M. A.; Melendez, M.

    2003-01-01

    A detailed analysis of the radiative and Auger de-excitation channels of K-shell vacancy states in Fe II-Fe IX has been carried out. Level energies, wavelengths, A-values, Auger rates and fluorescence yields have been calculated for the lowest fine-structure levels populated by photoionization of the ground state of the parent ion. Different branching ratios, namely K alpha 2/K alpha 1, K beta/K alpha, KLM/KLL, KMM/KLL, and the total K-shell fluorescence yields, omega(sub k), obtained in the present work have been compared with other theoretical data and solid-state measurements, finding good general agreement with the latter. The Kalpha 2/K alpha l ratio is found to be sensitive to the excitation mechanism. From these comparisons it has been possible to estimate an accuracy of approx.10% for the present transition probabilities.

  12. Prolactin-stimulated mitogenesis in the Nb2 rat lymphoma cell: Lack of protoporphyrin IX effects

    SciTech Connect

    Gerrish, K.E.; Putnam, C.W.; Laird, H.E. II )

    1990-01-01

    Pharmacological characterization of the Nb2 cell peripheral-type benzodiazepine receptor (PBR) was determined using selected 1,4-benzodiazepines, PK 11195, and protoporphyrin IX (PPIX) to compete for specific ({sup 3}H) Ro5-4864 binding. These data suggest that PPIX possesses an affinity for the Nb2 cell PBR. We have previously reported that the peripheral benzodiazepine ligands, Ro5-4864 and PK 11195, modulate prolactin-stimulated mitogenesis in the Nb2 cell. In contrast, PPIX, a putative endogenous ligand for the PBR had no effect on prolactin-stimulated mitogenesis in the Nb2 cell over the concentration range from 10{sup {minus}15} M to 10{sup {minus}6} M. Taken together these data show that PPIX has an affinity for the Nb2 cell PBR but does not modulate prolactin-stimulated mitogenesis at concentrations which should bind to the Nb2 cell PBR.

  13. Weld Residual Stress and Distortion Analysis of the ARES I-X Upper Stage Simulator (USS)

    NASA Technical Reports Server (NTRS)

    Raju, Ivatury; Dawicke, David; Cheston, Derrick; Phillips, Dawn

    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). 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. While the main focus of this paper is a discussion of the weld modeling procedures and results for the USS, a short summary of the CIFS assessment is provided.

  14. Distribution of Lunar craters according to morphology from Ranger VIII and IX photographs

    USGS Publications Warehouse

    Trask, N.J.

    1967-01-01

    A classification of the craters photographed by the Ranger VIII and IX missions into four categories according to relative sharpness shows that at diameters of 100 meters, the predominant craters have broad rims and low depth-diameter ratios and are partly covered with smaller craters which generally have sharper rims and higher depth-diameter ratios but include all classes. If competing processes of crater formation and destruction are responsible for the mix of crater types observed, an abrupt increase in the proportion of sharp craters suggests an intense episode of crater destruction to produce a smoothed surface that was subsequently recratered. Data comparable to those presented can readily be obtained from Lunar Orbiter photographs to determine if an increase in the proportion of sharp craters is present over more extensive areas and to test various cratering histories that may account for it. ?? 1967.

  15. Quarantine in times of emergency: the scope of s 51(ix) of the Constitution.

    PubMed

    Reynolds, Christopher

    2004-11-01

    This article explores the scope of s 51(ix) of the Constitution, the power of the Commonwealth to make laws with respect to "quarantine". While this power has sustained the Quarantine Act without a challenge since 1908, it may be that future national public health emergencies, such as epidemics or bioterrorism, will (as has happened in other countries) demand a level of federal preparedness that requires augmented public health powers at a national level. If so, will the scope of the quarantine power, as determined by the High Court, be wide enough allow the Commonwealth to implement these powers? While there is some advantage in a national approach, there is also some authority suggesting that the quarantine power could not extend to domestic public health controls. If there is uncertainty about the scope of the power, what are the options? Should there be another approach, with the States, Territories and the Commonwealth moving towards uniform legislation and co-operative arrangements?

  16. New developments in fluorescence detection of ALA-induced protoporphyrin IX for cancer localization

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Betz, Christian; Bise, Karl; Brand, P.; Gamarra, Fernando; Haeussinger, Karl; Hillemanns, Peter; Huber, Rudolf M.; Knuechel, Ruth; Kriegmair, M.; Leunig, Andreas; Pichler, J.; Rick, Kai; Schulz, H.; Stanzel, F.; Stocker, Susanne; Wagner, Simon; Weigandt, H.

    1997-12-01

    After the very promising clinical results for the detection of bladder cancer in urology, preclinical and clinical studies on aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) are preformed in various disciplines now. This paper provides a brief overview of the progress on 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT performed in collaboration with the Laser Research Laboratory at the Department of Urology of the Ludwig-Maximilians-University in Munich. Five-ALA can be applied either topically or systemically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, seems to be indispensable for a reliable tumor localization.

  17. Ares I-X Upper Stage Simulator Compartment Pressure Comparisons During Ascent

    NASA Technical Reports Server (NTRS)

    Downs. William J.; Kirchner, Robert D.; McLachlan, Blair G.; Hand, Lawrence A.; Nelson, Stuart L.

    2011-01-01

    Predictions of internal compartment pressures are necessary in the design of interstage regions, systems tunnels, and protuberance covers of launch vehicles to assess potential burst and crush loading of the structure. History has proven that unexpected differential pressure loads can lead to catastrophic failure. Pressures measured in the Upper Stage Simulator (USS) compartment of Ares I-X during flight were compared to post-flight analytical predictions using the CHCHVENT chamber-to-chamber venting analysis computer program. The measured pressures were enveloped by the analytical predictions for most of the first minute of flight but were outside of the predictions thereafter. This paper summarizes the venting system for the USS, discusses the probable reasons for the discrepancies between the measured and predicted pressures, and provides recommendations for future flight vehicles.

  18. 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.

  19. 5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII.

    PubMed

    Cvijetić, Ilija N; Tanç, Muhammet; Juranić, Ivan O; Verbić, Tatjana Ž; Supuran, Claudiu T; Drakulić, Branko J

    2015-08-01

    Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 μM). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho- and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 μM. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors.

  20. 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.

  1. Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas

    PubMed Central

    Viikilä, Pia; Kivelä, Antti J; Mustonen, Harri; Koskensalo, Selja; Waheed, Abdul; Sly, William S; Pastorek, Jaromir; Pastorekova, Silvia; Parkkila, Seppo; Haglund, Caj

    2016-01-01

    AIM To investigate expression of four alpha-carbonic anhydrases (CAs) in colorectal carcinomas (CRC) and compare the results with patients’ survival. METHODS Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA II, CA VII, CA IX, and CA XII. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients’ survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients’ age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data. RESULTS CA II and CA XII staining intensities correlated with patients’ survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA II intensity increased the hazard ratio to 1.19 fold (CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA XII staining intensity with survival of CRC patients (HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA XII immunostaining did not correlate to the patients’ survival (P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA II staining was found. Increased extent of CA II had a significant hazard ratio among patients 65 years and older (1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA VII (intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA IX (intensity P = 0.879, extent P = 0.315, Kaplan-Meier analysis) immunostaining results and survival, or the other parameters. CONCLUSION The present findings indicate that CA II and CA XII could be useful in predicting survival in CRC. PMID:27688658

  2. Seth Nicholson's First Satellite Discovery: Jupiter IX and His Orbit for It

    NASA Astrophysics Data System (ADS)

    Osterbrock, Donald E.

    2006-12-01

    Seth B. Nicholson was a graduate astronomy student at the University of California in Berkeley when he discovered his first satellite in 1914. He was later to discover three more, after he had joined the Mount Wilson Observatory staff following his PhD in 1915. Nicholson had begun his thesis on the problem of computing an improved orbit for J VIII, which had been discovered by Melotte in England in 1908, a distant irregular satellite like J VI and J VII. Nicholson was taking photographic plates to measure the position of J VIII in the summer of 1914 with the Crossley 36-inch reflector of Lick Observatory. He was a teaching assistant at Berkeley that summer, but would go up to Mount Hamilton to observe on weekends in the dark of the moon, traveling by rail, stage (an automobile on a regular schedule between San Jose and the observatory) and interurban trolley car, and sleeping in a shed near the Crossley dome. He first saw J IX as a much fainter object with the same motion as J VIII on a plate he took in late July 1914, and realized it must be another satellite of the giant planet. Nicholson obtained his first orbit of J IX, which had by then become his new thesis topic, in September, and published a paper on it in early 1915. Its orbit, like that of J VIII, was retrograde and irregular, but it was considerably fainter. Nicholson, a loyal student of Armin O. Leuschner, the head of the Berkeley Astronomy Division, used his teacher's "short method" (or analytic method) to calculate the orbit.

  3. Ares I-X Range Safety Simulation Verification and Analysis IV and V

    NASA Technical Reports Server (NTRS)

    Tarpley, Ashley; Beaty, James; Starr, Brett

    2010-01-01

    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) flight data package to meet the RS trajectory data requirements defined in the Air Force Space Command Manual 91-710. Some products included in the flight data package were a nominal ascent trajectory, ascent flight envelope trajectories, and malfunction turn trajectories. These data are used by the Air Force s 45th Space Wing (45SW) to ensure Eastern Range public safety and to make flight termination decisions on launch day. Due to the criticality of the RS data in regards to public safety and mission success, 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. Multiple NASA centers and contractor organizations were assigned specific products to IV&V. The data generation and IV&V work was coordinated through the Launch Constellation Range Safety Panel s Trajectory Working Group, which included members from the prime and IV&V organizations as well as the 45SW. 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 ARES I-X RS product IV&V analysis, including the methodology used to verify inputs, simulation, and output data for an RS product. Additionally a discussion of lessons learned is presented to capture advantages and disadvantages to the IV&V processes used.

  4. PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets.

    PubMed

    Rathore, Vipul; Stapleton, Michelle A; Hillery, Cheryl A; Montgomery, Robert R; Nichols, Timothy C; Merricks, Elizabeth P; Newman, Debra K; Newman, Peter J

    2003-11-15

    Platelet adhesion at sites of vascular injury is mediated, in part, by interaction of the platelet plasma membrane glycoprotein (GP) Ib/V/IX complex with von Willebrand Factor (VWF) presented on collagen-exposed surfaces. Recent studies indicate that GPIb/V/IX may be functionally coupled with the Fc receptor gamma (FcR gamma)-chain, which, by virtue of its cytoplasmic immunoreceptor tyrosine-based activation motif, sends activation signals into the cell. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an inhibitory receptor that has previously been shown to negatively regulate platelet responses to collagen, which transduces activation signals via the GPVI/FcR gamma-chain complex. To determine whether PECAM-1 might similarly regulate signals emanating from GPIb/FcR gamma, we compared activation and aggregation responses to VWF of PECAM-1-positive and PECAM-1-deficient murine platelets. PECAM-1 and the FcR gamma-chain became rapidly tyrosine phosphorylated in platelets following botrocetin-induced VWF binding, but FcR gamma-chain tyrosine phosphorylation was delayed in PECAM-1-positive, versus PECAM-1-deficient, platelets. PECAM-1-deficient platelets were hyperaggregable to VWF, exhibited enhanced spreading and, under conditions of arterial flow, formed markedly larger thrombi on immobilized VWF than did wild-type platelets. Taken together, these data support the notion that engagement of the GPIb complex, in addition to sending activation signals, also initiates a negative feedback loop involving PECAM-1 that controls the rate and extent of platelet activation. PMID:12893757

  5. Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas

    PubMed Central

    Viikilä, Pia; Kivelä, Antti J; Mustonen, Harri; Koskensalo, Selja; Waheed, Abdul; Sly, William S; Pastorek, Jaromir; Pastorekova, Silvia; Parkkila, Seppo; Haglund, Caj

    2016-01-01

    AIM To investigate expression of four alpha-carbonic anhydrases (CAs) in colorectal carcinomas (CRC) and compare the results with patients’ survival. METHODS Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA II, CA VII, CA IX, and CA XII. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients’ survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients’ age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data. RESULTS CA II and CA XII staining intensities correlated with patients’ survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA II intensity increased the hazard ratio to 1.19 fold (CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA XII staining intensity with survival of CRC patients (HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA XII immunostaining did not correlate to the patients’ survival (P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA II staining was found. Increased extent of CA II had a significant hazard ratio among patients 65 years and older (1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA VII (intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA IX (intensity P = 0.879, extent P = 0.315, Kaplan-Meier analysis) immunostaining results and survival, or the other parameters. CONCLUSION The present findings indicate that CA II and CA XII could be useful in predicting survival in CRC.

  6. The structures of the carbohydrate moieties of bovine blood coagulation factor IX (Christmas factor).

    PubMed

    Mizuochi, T; Taniguchi, T; Fujikawa, K; Titani, K; Kobata, A

    1983-05-25

    Bovine blood coagulation factor IX (Christmas factor) contains four asparagine-linked sugar chains in one molecule. The sugar chains were quantitatively liberated as radioactive oligosaccharides from the polypeptide moiety by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. The structures of these sugar chains were determined by sequential exoglycosidase digestion in combination with methylation analysis. Bovine factor IX contained two unique penta- and tetrasialyl triantennary sugar chains with the structures shown below in addition to tetra-, tri-, and disialyl biantennary sugar chains of Sia alpha 2 leads to 3 Gal beta 1 leads 3(Sia alpha 2 leads to 6)GlcNAc beta 1 leads to 2Man alpha 1 leads to 6[Sia alpha 2 leads to 3Gal beta 1 leads to 3(Sia alpha 2 leads to 6)GlcNac beta 1 leads to 2Man alpha 1 leads to 3]Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc, Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6[Sia alpha 2 leads to 3Gal beta 1 leads to 3(Sia alpha 2 leads to 6)GlcNAc beta 1 leads to 2Man alpha 1 leads to 3]Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc, and Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc and their partially desialized forms.

  7. Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect

    PubMed Central

    1981-01-01

    Bovine skin fibroblasts accumulated protoporphyrin IX when incubated in culture with the porphyrin-heme precursor, delta-aminolevulinic acid (ALA). Fibroblasts from cattle homozygous for erythropoietic protoporphyria (EPP) and with the clinical symptoms of the disease accumulated approximately sixfold greater amounts of protoporphyrin IX than cells from normal control animals. Cells from obligatory heterozygous animals, which are clinically normal, accumulated an intermediate level of protoporphyrin IX. When these cells were incubated with ALA and CaMg EDTA, all types of cells accumulated approximately the same amount of protoporphyrin IX (approximately 500 nmol/mg protein), suggesting that ferrochelatase activity was equally low after inhibition by treatment with CaMg EDTA in all cells. Thus the ratio of protoporphyrin IX accumulation from ALA in cultures treated with CaMg EDTA compared with controls treated with ALA alone was greatest in normal cells, least in EPP cells, and intermediate in the heterozygote cells. These findings suggest that the amount of protoporphyrin IX accumulation from ALA reflects the extent of deficiency of ferrochelatase and is proportional to the dosage of abnormal EPP gene in cultured fibroblasts. Similarly, stimulation of porphyrin accumulation by CaMg EDTA reflects diminished ferrochelatase activity in these cells. Thus, the results of this study demonstrate the usefulness of estimating protoporphyrin IX formation from ALA for the detection of an EPP gene defect in cultured bovine skin fibroblasts. PMID:6788885

  8. Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

    PubMed Central

    Lange, N; Jichlinski, P; Zellweger, M; Forrer, M; Marti, A; Guillou, L; Kucera, P; Wagnières, G; Bergh, H van den

    1999-01-01

    Exogenous administration of 5-aminolaevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of protoporphyrin IX (PpIX) in photodynamic therapy (PDT) and fluorescence photodetection (PD). Recently, results have shown that the chemical modification of ALA into its more lipophilic esters circumvents limitations of ALA-induced PpIX like shallow penetration depth into deep tissue layers and inhomogeneous biodistribution and enhances the total PpIX formation. The present clinical pilot study assesses the feasibility and the advantages of a topical ALA ester-based fluorescence photodetection in the human bladder. In this preliminary study 5-aminolaevulinic acid hexylester (h-ALA) solutions, containing concentrations ranging from 4 to 16 mM, were applied intravesically to 25 patients. Effects of time and drug dose on the resulting PpIX fluorescence level were determined in vivo with an optical fibre-based spectrofluorometer. Neither local nor systemic side-effects were observed for the applied conditions. All conditions used yielded a preferential PpIX accumulation in the neoplastic tissue. Our clinical investigations indicate that with h-ALA a twofold increase of PpIX fluorescence intensity can be observed using 20-fold lower concentrations as compared to ALA. © 1999 Cancer Research Campaign PMID:10389995

  9. A role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia and mortality

    PubMed Central

    Yin, Hong; Stojanovic, Aleksandra; Xu, Weidong; Corken, Adam; Zakharov, Alexander; Qian, Feng; Pavlovic, Sasha; Krbanjevic, Aleksandar; Lyubimov, Alexander V.; Wang, Zaijie J.; Ware, Jerry; Du, Xiaoping

    2014-01-01

    Objective Poor prognosis of sepsis is associated with bacterial lipopolysaccharide (LPS)-induced intravascular inflammation, microvascular thrombosis, thrombocytopenia, and disseminated intravascular coagulation. Platelets are critical for thrombosis, and there have been increasing evidence of the importance of platelets in endotoxemia. The platelet adhesion receptor, the glycoprotein Ib-IX complex (GPIb-IX), mediates platelet adhesion to inflammatory vascular endothelium and exposed subendothelium. Thus, we have investigated the role of GPIb-IX in LPS-induced platelet adhesion, thrombosis and thrombocytopenia. Approach and Results LPS-induced mortality is significantly decreased in mice expressing a functionally deficient mutant of GPIbα. Furthermore, we have developed a micellar peptide inhibitor, MPαC, which selectively inhibits the VWF-binding function of GPIb-IX and GPIb-IX-mediated platelet adhesion under flow without affecting GPIb-IX-independent platelet activation. MPαC inhibits platelet adhesion to LPS-stimulated endothelial cells in vitro and alleviates LPS-induced thrombosis in glomeruli in mice. Importantly, MPαC reduces mortality in LPS-challenged mice, suggesting a protective effect of this inhibitor during endotoxemia. Interestingly, MPαC, but not the integrin antagonist, Integrilin, alleviated LPS-induced thrombocytopenia. Conclusion These data indicate an important role for the platelet adhesion receptor GPIb-IX in LPS-induced thrombosis and thrombocytopenia, and suggest the potential of targeting GPIb as an anti-platelet strategy in managing endotoxemia. PMID:24051142

  10. 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.

  11. 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

  12. 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

  13. A simple technique to reduce epistaxis and nasopharyngeal trauma during nasotracheal intubation in a child with factor IX deficiency having dental restoration.

    PubMed

    Delgado, Anita V; Sanders, John C

    2004-10-01

    Epistaxis and airway trauma are often associated with nasotracheal intubation. We describe a patient with Factor IX deficiency who required nasotracheal intubation. An inexpensive, nonproprietary, rapid technique was used to reduce the trauma of intubation.

  14. Comparison of amino acid sequence of bovine coagulation Factor IX (Christmas Factor) with that of other vitamin K-dependent plasma proteins.

    PubMed

    Katayama, K; Ericsson, L H; Enfield, D L; Walsh, K A; Neurath, H; Davie, E W; Titani, K

    1979-10-01

    The amino acid sequence of bovine blood coagulation Factor IX (Christmas Factor) is presented and compared with the sequences of other vitamin K-dependent plasma proteins and pancreatic trypsinogen. The 416-residue sequence of Factor IX was determined largely by automated Edman degradation of two large segments, containing 181 and 235 residues, isolated after activating Factor IX with a protease from Russell's viper venom. Subfragments of the two segments were produced by enzymatic digestion and by chemical cleavage of methionyl, tryptophyl, and asparaginyl-glycyl bonds. Comparison of the amino acid sequences of Factor IX, Factor X, and Protein C demonstrates that they are homologous throughout. Their homology with prothrombin, however, is restricted to the amino-terminal region, which is rich in gamma-carboxyglutamic acid, and the carboxyl-terminal region, which represents the catalytic domain of these proteins and corresponds to that of pancreatic serine proteases.

  15. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

    PubMed Central

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-01-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas. PMID:23577290

  16. Commissioning of a Varian Clinac iX 6 MV photon beam using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Dirgayussa, I. Gde Eka; Yani, Sitti; Rhani, M. Fahdillah; Haryanto, Freddy

    2015-09-01

    Monte Carlo modelling of a linear accelerator is the first and most important step in Monte Carlo dose calculations in radiotherapy. Monte Carlo is considered today to be the most accurate and detailed calculation method in different fields of medical physics. In this research, we developed a photon beam model for Varian Clinac iX 6 MV equipped with MilleniumMLC120 for dose calculation purposes using BEAMnrc/DOSXYZnrc Monte Carlo system based on the underlying EGSnrc particle transport code. Monte Carlo simulation for this commissioning head LINAC divided in two stages are design head Linac model using BEAMnrc, characterize this model using BEAMDP and analyze the difference between simulation and measurement data using DOSXYZnrc. In the first step, to reduce simulation time, a virtual treatment head LINAC was built in two parts (patient-dependent component and patient-independent component). The incident electron energy varied 6.1 MeV, 6.2 MeV and 6.3 MeV, 6.4 MeV, and 6.6 MeV and the FWHM (full width at half maximum) of source is 1 mm. Phase-space file from the virtual model characterized using BEAMDP. The results of MC calculations using DOSXYZnrc in water phantom are percent depth doses (PDDs) and beam profiles at depths 10 cm were compared with measurements. This process has been completed if the dose difference of measured and calculated relative depth-dose data along the central-axis and dose profile at depths 10 cm is ≤ 5%. The effect of beam width on percentage depth doses and beam profiles was studied. Results of the virtual model were in close agreement with measurements in incident energy electron 6.4 MeV. Our results showed that photon beam width could be tuned using large field beam profile at the depth of maximum dose. The Monte Carlo model developed in this study accurately represents the Varian Clinac iX with millennium MLC 120 leaf and can be used for reliable patient dose calculations. In this commissioning process, the good criteria of dose

  17. Commissioning of a Varian Clinac iX 6 MV photon beam using Monte Carlo simulation

    SciTech Connect

    Dirgayussa, I Gde Eka Yani, Sitti; Haryanto, Freddy; Rhani, M. Fahdillah

    2015-09-30

    Monte Carlo modelling of a linear accelerator is the first and most important step in Monte Carlo dose calculations in radiotherapy. Monte Carlo is considered today to be the most accurate and detailed calculation method in different fields of medical physics. In this research, we developed a photon beam model for Varian Clinac iX 6 MV equipped with MilleniumMLC120 for dose calculation purposes using BEAMnrc/DOSXYZnrc Monte Carlo system based on the underlying EGSnrc particle transport code. Monte Carlo simulation for this commissioning head LINAC divided in two stages are design head Linac model using BEAMnrc, characterize this model using BEAMDP and analyze the difference between simulation and measurement data using DOSXYZnrc. In the first step, to reduce simulation time, a virtual treatment head LINAC was built in two parts (patient-dependent component and patient-independent component). The incident electron energy varied 6.1 MeV, 6.2 MeV and 6.3 MeV, 6.4 MeV, and 6.6 MeV and the FWHM (full width at half maximum) of source is 1 mm. Phase-space file from the virtual model characterized using BEAMDP. The results of MC calculations using DOSXYZnrc in water phantom are percent depth doses (PDDs) and beam profiles at depths 10 cm were compared with measurements. This process has been completed if the dose difference of measured and calculated relative depth-dose data along the central-axis and dose profile at depths 10 cm is ≤ 5%. The effect of beam width on percentage depth doses and beam profiles was studied. Results of the virtual model were in close agreement with measurements in incident energy electron 6.4 MeV. Our results showed that photon beam width could be tuned using large field beam profile at the depth of maximum dose. The Monte Carlo model developed in this study accurately represents the Varian Clinac iX with millennium MLC 120 leaf and can be used for reliable patient dose calculations. In this commissioning process, the good

  18. PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX Secretion System

    PubMed Central

    Veith, Paul D.; Butler, Catherine A.; Nor Muhammad, Nor A.; Chen, Yu-Yen; Slakeski, Nada; Peng, Benjamin; Zhang, Lianyi; Dashper, Stuart G.; Cross, Keith J.; Cleal, Steven M.; Moore, Caroline; Reynolds, Eric C.

    2016-01-01

    Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion system (T9SS) to export proteins across the outer membrane (OM), including virulence factors such as the gingipains. The secreted proteins have a conserved carboxy-terminal domain essential for type IX secretion that is cleaved upon export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative analyses of 24 Bacteroidetes genomes identified ten putative novel components of the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the PG1058 structure predicted a novel N- to C-terminal architecture comprising a tetratricopeptide repeat (TPR) domain, a β-propeller domain, a carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in loss of both colonial pigmentation and surface-associated proteolytic activity; a phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA analyses indicated A-LPS was produced and present on the pg1058 mutant cell surface although it was not linked to T9SS substrate proteins. This indicated that PG1058 is crucial for export of T9SS substrates but not for the translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS analyses of subcellular fractions. The structural prediction and localisation of PG1058 suggests that it may have a role as an essential scaffold linking the periplasmic and OM components of the T9SS. PMID:27711252

  19. Distribution of protoporphyrin IX in Bowen's disease and basal cell carcinomas treated with topical 5-aminolaevulinic acid

    NASA Astrophysics Data System (ADS)

    Roberts, David J.; Stables, G. I.; Ash, D. V.; Brown, Stanley B.

    1995-03-01

    We have used ultra-low light level fluorescence microscopy to examine the suggestion that the relatively poor response of human basal cell carcinomas (BCC) to topical 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) arises from limited drug penetration into the lesion. The distribution of ALA-induced protoporphyrin IX (PpIX) in human BCC and Bowen's disease was examined and, in almost all cases, was found to be most intense in those regions of tumor immediately adjacent to the dermis. This distribution was independent of tumor type, and did not appear to be affected by tumor depth in the skin. It is suggested that ALA penetration may not limit the efficacy of ALA-PDT in the treatment of BCC. Failure of superficial ALA-based PDT in basal cell carcinoma may, instead, be related to the histological structure of this type of lesion.

  20. 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.

  1. Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII.

    PubMed

    Durgun, Mustafa; Turkmen, Hasan; Ceruso, Mariangela; Supuran, Claudiu T

    2016-03-01

    Imine derivatives were obtained by condensation of sulfanilamide with substituted aromatic aldehydes. The Schiff bases were thereafter reduced with sodium borohydride, leading to the corresponding amines, derivatives of 4-sulfamoylphenyl-benzylamine. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). We noted that the compounds incorporating secondary amine moieties showed a better inhibitory activity against all CA isozymes compared to the corresponding Schiff bases. Low nanomolar CA II, IX and XII inhibitors were detected, whereas the activity against hCA I was less potent. The secondary amines incorporating sulfonamide or similar zinc-binding groups, poorly investigated chemotypes for designing metalloenzyme inhibitors, may offer interesting opportunities in the field due to the facile preparation and possibility to explore a vast chemical space. PMID:26803577

  2. The Potential of Liposomes with Carbonic Anhydrase IX to Deliver Anticancer Ingredients to Cancer Cells in Vivo

    PubMed Central

    Ng, Huei Leng Helena; Lu, Aiping; Lin, Ge; Qin, Ling; Yang, Zhijun

    2014-01-01

    Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and active cellular uptake. Here, we highlight the features of immunoliposomes that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While a large number of studies has been published, the emphasis here is placed on the carbonic anhydrase IX (CA-IX) and the conjugated liposomes that are likely to open a new chapter on drug delivery system by using immunoliposomes to deliver anticancer ingredients to cancer cells in vivo. PMID:25547490

  3. Driver's Licences for the handicapped in Canada.

    ERIC Educational Resources Information Center

    Csapo, Marg; Clarke, Bryan R.

    1985-01-01

    The article reviews Canada's Guide for Physicians in Determining Fitness to Drive a Vehicle and then considers sections of provincial motor vehicle acts that regulate the issuance of licenses to the handicapped. (CL)

  4. Modeling the Ne IX Triplet Spectral Region of Capella with the Chandra and XMM-Newton Gratings

    NASA Astrophysics Data System (ADS)

    Ness, Jan-Uwe; Brickhouse, Nancy S.; Drake, Jeremy J.; Huenemoerder, David P.

    2003-12-01

    High-resolution X-ray spectroscopy with the diffraction gratings of Chandra and XMM-Newton offers new chances to study a large variety of stellar coronal phenomena. A popular X-ray calibration target is Capella, which has been observed with all gratings with significant exposure times. We gathered together all available data of the High Energy Transmission Grating Spectrometer (HETGS; 155 ks), Low Energy Transmission Grating Spectrometer (LETGS; 219 ks), and Reflection Grating Spectrometer (RGS; 53 ks) for comparative analysis, focusing on the Ne IX triplet at around 13.5 Å, a region that is severely blended by strong iron lines. We identify 18 emission lines in this region of the High-Energy Grating (HEG) spectrum, including many from Fe XIX, and find good agreement with predictions from a theoretical model constructed using the Astrophysical Plasma Emission Code. The model uses an emission measure distribution derived from Fe XV to Fe XXIV lines. The success of the model is due in part to the inclusion of accurate wavelengths from laboratory measurements. While these 18 emission lines cannot be isolated in the LETGS or RGS spectra, their wavelengths and fluxes as measured with HEG are consistent with the lower resolution spectra. In the Capella model for HEG, the weak intercombination line of Ne IX is significantly blended by iron lines, which contribute about half the flux. After accounting for blending in the He-like diagnostic lines, we find the density to be consistent with the low-density limit (ne<2×1010 cm-3) however, the electron temperature indicated by the Ne IX G-ratio is surprisingly low (~2 MK) compared to the peak of the emission measure distribution (~6 MK). Models show that the Ne IX triplet is less blended in cooler plasmas and in plasmas with an enhanced neon-to-iron abundance ratio.

  5. Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice

    PubMed Central

    Toby, Garabet G.; Liu, Tongyao; Buyue, Yang; Zhang, Xin; Bitonti, Alan J.; Pierce, Glenn F.; Sommer, Jurg M.; Jiang, Haiyan; Peters, Robert T.

    2016-01-01

    Introduction Hemophilia B is an inherited X chromosome–linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans. Materials and Methods Procoagulant properties of rFIXFc and rFIX (BENEFIX®) were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT) and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models. Results and Conclusions The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice. PMID:26840952

  6. Synthesis and in Vivo Biological Evaluation of (68)Ga-Labeled Carbonic Anhydrase IX Targeting Small Molecules for Positron Emission Tomography.

    PubMed

    Sneddon, Deborah; Niemans, Raymon; Bauwens, Matthias; Yaromina, Ala; van Kuijk, Simon J A; Lieuwes, Natasja G; Biemans, Rianne; Pooters, Ivo; Pellegrini, Paul A; Lengkeek, Nigel A; Greguric, Ivan; Tonissen, Kathryn F; Supuran, Claudiu T; Lambin, Philippe; Dubois, Ludwig; Poulsen, Sally-Ann

    2016-07-14

    Tumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [(68)Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing (68)Ga for preclinical CA IX imaging are scarce, and this is one of the first effective (68)Ga compounds reported for PET imaging of CA IX. PMID:27322137

  7. Efficiency Of The Photodynamic Therapy Using Gold Nanoparticles (np-Au) And PpIX Induced And Not Induced

    SciTech Connect

    Maldonado-Alvarado, Elizabeth; Ramon-Gallegos, Eva; Arenas-Huertero, Francisco jesus; Reyes-Arellano, Alicia; Sanchez-Espindola, Maria Esther; Jimenez-Perez, Jose Luis; Cruz-Orea, Alfredo

    2008-08-11

    The use of gold nanoparticles (np-Au) to eliminate cancer has proved to be very effective due to the fact that cancerous cells accumulate it 600% more than healthy cells. In addition they have a high capacity of absorption and dispersion of light. Therefore, the effectiveness of photodynamic therapy (PDT) could be improved by the simultaneous use of np-Au and photosensitizes (Ps), emphasizing the high efficiency of the PDT to diagnose and to treat pre-malignant and malignant processes. The aim of this work was to determine the efficiency of PDT using np-Au and protoporphyrin IX (PpIX) induced and not induced by the {delta}-aminolevulinic acid (ALA). It were found the conditions of synthesis of hydrosoluble np-Au, and were characterized by transmission electronic microscopy (TEM) and UV-VIS spectroscopy. It was realized a kinetic by TEM to determine the cellular incorporation time of np-Au, the maximum incorporation of np-Au was of 16 h. PDT was applied using different doses of np-Au and photosensitizers. It was observed that the use of PDT simultaneously with np-Au did not increase the mortality of HeLa cells. In the case of C33, when PpIX not induced is used as photosensitizer simultaneously with np-Au, the mortality increased 20%.

  8. Fission Rate Ratios of FCA-IX Assemblies as Integral Experiment for Assessment of TRU's Fission Cross Sections

    NASA Astrophysics Data System (ADS)

    Fukushima, Masahiro; Tsujimoto, Kazufumi; Okajima, Shigeaki

    2016-03-01

    At the fast critical assembly (FCA) of JAEA, central fission rate ratios for TRU such as 237Np, 238Pu, 239Pu, 242Pu, 241Am, 243Am, and 244Cm were measured in the seven uraniumfueled assemblies (FCA-IX assemblies) with systematically changed neutron spectra. The FCA-IX assemblies were constructed with simplicity both in geometry and composition. By virtue of these FCA-IX assemblies where the simple combinations of uranium fuel and diluent (graphite and stainless steel) in their core regions were systematically varied, the neutron spectra of them cover from the intermediate to fast one. Taking their advantages, benchmark models with respect to the central fission rate ratios had been recently developed for the evaluation of the TRU's fission cross sections. As an application of these benchmark models, the Japanese Evaluated Nuclear Data Library JENDL-4.0 was utilized by a Monte Carlo calculation code. Several results show large discrepancies between the calculation and experimental values. The benchmark models would be well suited for the evaluation and modification of the nuclear data for the TRU's fission cross sections.

  9. The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations

    NASA Astrophysics Data System (ADS)

    Morgan, Janet; Petrucci, Cara M.

    2009-06-01

    Protoporphyrin IX (PpIX) synthesized endogenously from 5-aminolevulinic acid (ALA), is effluxed from cells expressing the ATP-dependent transporter ABCG2. Side population (SP) cells (named for their low red/blue fluorescence distribution in flow cytometry plots with ABCG2 substrates such as Hoechst) are postulated to contain cancer stem cells (CSC). The SP in U87 (human gliblastoma cell line) were more resistant to ALA-PDT than NON-SP cells. Inhibiting ABCG2 activity with the tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) during incubation with ALA increased PpIX in the SP by preventing its efflux and decreased the SP after subsequent PDT, enhancing phototoxicity. Evasion of SP cells from ALA-PDT could cause tumor recurrence from CSC. Manipulation of ABCG2 levels on the SP with small molecule modulators may be a potential strategy for enhancing PDT by decreasing the amount of substrate photosensitizer extruded from cells and lowering the threshold for phototoxicity.

  10. Lack of a surface layer in Tannerella forsythia mutants deficient in the type IX secretion system

    PubMed Central

    Narita, Yuka; Sato, Keiko; Yukitake, Hideharu; Shoji, Mikio; Nakane, Daisuke; Nagano, Keiji; Yoshimura, Fuminobu; Naito, Mariko

    2014-01-01

    Tannerella forsythia, a Gram-negative anaerobic bacterium, is an important pathogen in periodontal disease. This bacterium possesses genes encoding all known components of the type IX secretion system (T9SS). T. forsythia mutants deficient in genes orthologous to the T9SS-encoding genes porK, porT and sov were constructed. All porK, porT and sov single mutants lacked the surface layer (S-layer) and expressed less-glycosylated versions of the S-layer glycoproteins TfsA and TfsB. In addition, these mutants exhibited decreased haemagglutination and increased biofilm formation. Comparison of the proteins secreted by the porK and WT strains revealed that the secretion of several proteins containing C-terminal domain (CTD)-like sequences is dependent on the porK gene. These results indicate that the T9SS is functional in T. forsythia and contributes to the translocation of CTD proteins to the cell surface or into the extracellular milieu. PMID:25023245

  11. Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function.

    PubMed

    Tajnik, Mojca; Rogalska, Malgorzata Ewa; Bussani, Erica; Barbon, Elena; Balestra, Dario; Pinotti, Mirko; Pagani, Franco

    2016-05-01

    Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a modified U1snRNP particle, through an SRSF2-dependent enhancement mechanism. We discovered that synonymous mutations and missense substitutions associated to a partial FIX secretion defect represent targets for this therapy as the resulting spliced-corrected proteins maintains normal FIX coagulant specific activity. Thus, splicing and protein alterations contribute to define at the molecular level the disease-causing effect of a number of exonic mutations in coagulation FIX exon 5. In addition, our results have a significant impact in the development of splicing-switching therapies in particular for mutations that affect both splicing and protein function where increasing the amount of a correctly spliced protein can circumvent the basic functional defects. PMID:27227676

  12. Projects from Federal Region IX: Department of Energy Appropriate Energy Technology Program. Part II

    SciTech Connect

    Case, C.W.; Clark, H.R.; Kay, J.; Lucarelli, F.B.; Rizer, S.

    1980-01-01

    Details and progress of appropriate energy technology programs in Region IX are presented. In Arizona, the projects are Solar Hot Water for the Prescott Adult Center and Solar Prototype House for a Residential Community. In California, the projects are Solar AquaDome Demonstration Project; Solar Powered Liquid Circulating Pump; Appropriate Energy Technology Resource Center; Digester for Wastewater Grown Aquatic Plants; Performance Characteristics of an Anaerobic Wastewater Lagoon Primary Treatment System; Appropriate Energy/Energy Conservation Demonstration Project; Solar Energy for Composting Toilets; Dry Creek Rancheria Solar Demonstration Projects; Demonstration for Energy Retrofit Analysis and Implementation; and Active Solar Space Heating System for the Integral Urban House. In Hawaii, the projects are: Java Plum Electric; Low-Cost Pond Digesters for Hawaiian Pig Farm Energy Needs; Solar Beeswax Melter; Methane Gas Plant for Operating Boilers and Generating Steam; and Solar Water Heating in Sugarcane Seed-Treatment Plants. A Wind-Powered Lighted Navigation Buoys Project for Guam is also described. A revised description of the Biogas Energy for Hawaiian Small Farms and Homesteads is given in an appendix.

  13. Iron(III) protoporphyrin IX complexes of the antimalarial Cinchona alkaloids quinine and quinidine.

    PubMed

    de Villiers, Katherine A; Gildenhuys, Johandie; le Roex, Tanya

    2012-04-20

    The antimalarial properties of the Cinchona alkaloids quinine and quinidine have been known for decades. Surprisingly, 9-epiquinine and 9-epiquinidine are almost inactive. A lack of definitive structural information has precluded a clear understanding of the relationship between molecular structure and biological activity. In the current study, we have determined by single crystal X-ray diffraction the structures of the complexes formed between quinine and quinidine and iron(III) protoporphyrin IX (Fe(III)PPIX). Coordination of the alkaloid to the Fe(III) center is a key feature of both complexes, and further stability is provided by an intramolecular hydrogen bond formed between a propionate side chain of Fe(III)PPIX and the protonated quinuclidine nitrogen atom of either alkaloid. These interactions are believed to be responsible for inhibiting the incorporation of Fe(III)PPIX into crystalline hemozoin during its in vivo detoxification. It is also possible to rationalize the greater activity of quinidine compared to that of quinine.

  14. Sedimentological and petryphysical characterization of the Cogollo Group, Cretaceous, Block IX, Maracaibo Lake

    SciTech Connect

    Munoz, P.; Verenzuela, X. ); Franssen, R.; Vahrenramp, V. )

    1993-02-01

    The present study contains the most important results from the sedimentological and petrophysical analysis of two Cretaceous cores (SVS-225/229) located in the Block IX of Lake maracaibo, northwestern Venezuela. In order to better define and locate sites for exploratory drilling, a study was undertaken to describe calcareous facies and their relationship to matrix porosity, open fractures, sedimentary and flow units. The sedimentary units were grouped on the basis similar characteristics and vertical and horizontal extrapolation potential. They also serve as indicators to determine the major sedimentary environments and help define the sedimentological model for the section under study. The most promising calcareous facies are composed of dolomites, wackestones, packstones and grainstones. They are all related to the open fractures, their orientation and density. The flow units were determined using these characteristics together with the oil impregnation observed in the cores. Also they were found to be mainly related to the coarsening upper sedimentary sequences. The identification of these units and their correlation to neighboring areas is useful for in the effectively managing processes for the Cretaceous oil reservoirs.

  15. Temporal fluctuations in the SERRS spectra of single iron protoporphyrin IX molecule

    NASA Astrophysics Data System (ADS)

    Bizzarri, Anna Rita; Cannistraro, Salvatore

    2003-05-01

    Surface enhanced resonance Raman spectra of Fe-protoporphyrin IX, adsorbed on silver colloidal nanoparticles immobilized onto a polymer-coated glass slide have been investigated at very low concentrations. The spectra exhibit drastic temporal fluctuations on a time scale of seconds in both line frequency and intensity; such a trend suggesting that the single molecule limit is approached. Sequences of spectra have been analyzed in terms of an underlying continuum and of Raman peaks superimposed on this continuum. A statistical analysis of the spectrum intensity has allowed us to put into evidence that main contribution to the intensity fluctuations arises from the continuum. In addition, a high correlation between the total integrated intensity and the intensity detected at different Raman peaks has been revealed. Furthermore, the ratio between the intensity detected in correspondence of different FePP vibrational modes shows a temporal variability likely reflecting the intrinsic dynamics of the molecule. All these findings have been ascribed to a desorption-adsorption mechanism of the molecules at the silver surface.

  16. Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice

    PubMed Central

    Franchini, Massimo; Mannucci, Pier Mannuccio

    2011-01-01

    The management of patients with congenital haemophilia who develop alloantibodies against factors of the propagation phase of blood coagulation, commonly known as inhibitors, is the most important challenge facing haemophilia caregivers at present, as this complication not only compromises the efficacy of replacement therapy but also consumes an enormous amount of economic resources. Development of inhibitors further complicates the clinical course of severe haemophilia, with a prevalence of up to 30% in patients with haemophilia A (factor VIII deficiency) and up to 5% in those with haemophilia B (factor IX deficiency) and haemophilia C (factor XI deficiency). While the short-term goal of treatment of patients who develop alloantibodies is the control of bleeding, the eradication of the inhibitor is the main long-term goal. The management of severe bleeding episodes and the eradication of the autoantibody are also the mainstays of treatment of patients with acquired haemophilia, a rare but life-threatening haemorrhagic condition characterized by the development of inhibitory autoantibodies against coagulation factor VIII. The most recent options available for treating patients with congenital haemophilia complicated by inhibitors and acquired haemophilia because of autoantibodies against factor VIII are summarized in this review article. PMID:21204915

  17. Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues.

    PubMed

    Kitchen, S; Kershaw, G; Tiefenbacher, S

    2016-07-01

    The recent development of modified recombinant factor VIII (FVIII) and factor IX (FIX) therapeutic products with extended half-lives will create challenges for the haemostasis laboratory in obtaining recovery estimates of these products in clinical samples using existing assays. The new long-acting therapeutic concentrates contain molecular modifications of Fc fusion, site-specific of polyethylene glycol or albumin fusion. The optimum methods for monitoring each new product will need to be assessed individually and laboratories should select an assay which gives similar results to the assay used to assign potency to the product in question. For some extended half-life FVIII and FIX products some one stage assays are entirely unsuitable for monitoring purposes. For most products and assay reagents studied so far, and reviewed in this manuscript, chromogenic FVIII or FIX assays can be safely used with conventional plasma standards. If one stage assays are used then they should be performed using carefully selected reagents/methods which have been shown to recover activity close to the labelled potency for the specific product being monitored. PMID:27405680

  18. Imaging protoporphyrin IX fluorescence with a time-domain FMT/microCT system

    NASA Astrophysics Data System (ADS)

    Leblond, Frederic; Kepshire, Dax; O'Hara, Julia A.; Dehghani, Hamid; Srinivasan, Subha; Mincu, N.; Hutchins, M.; Khayat, M.; Pogue, B. W.

    2009-02-01

    Fluorescence molecular tomography (FMT) has the potential to become a powerful quantitative research tool for pre-clinical applications such as evaluating the efficacy of experimental drugs. In this paper, we show how a time-domain FMT/microCT instrument can in principle be used to monitor volumetric fluorescence intensity over time for low fluorophore concentration levels. The experimental results we present relate to Protoporphyrin IX which has a quantum efficiency as much as two orders of magnitude lower compared to more conventional extrinsic dyes used for molecular imaging (e.g., Alexa Fluor dyes, Cyanine dyes). Our results highlight the high sensitivity of the single photon counting technology on which the optical system we have built is based. In conjunction with this system we have developed a diffuse optical fluorescence reconstruction technique that is robust and shown here to perform adequately even in cases when the contribution of noise to the data is important. Related to this, we show that the regularization scheme we have developed is reliable even for low fluorophore concentration values and that no adjustment of the regularization parameter needs to be made for different levels of noise. This generic reconstruction approach insures that images reconstructed from data sets acquired at different times and for different fluorescence levels can be compared on an equal footing.

  19. Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

    PubMed Central

    Chang, David; Garcia, Rebecca A.; Akers, Kevin S.; Mende, Katrin; Murray, Clinton K.; Wenke, Joseph C.; Sanchez, Carlos J.

    2016-01-01

    Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. PMID:26999163

  20. Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function

    PubMed Central

    Bussani, Erica; Barbon, Elena; Pinotti, Mirko; Pagani, Franco

    2016-01-01

    Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a modified U1snRNP particle, through an SRSF2-dependent enhancement mechanism. We discovered that synonymous mutations and missense substitutions associated to a partial FIX secretion defect represent targets for this therapy as the resulting spliced-corrected proteins maintains normal FIX coagulant specific activity. Thus, splicing and protein alterations contribute to define at the molecular level the disease-causing effect of a number of exonic mutations in coagulation FIX exon 5. In addition, our results have a significant impact in the development of splicing-switching therapies in particular for mutations that affect both splicing and protein function where increasing the amount of a correctly spliced protein can circumvent the basic functional defects. PMID:27227676

  1. ComIXS on BACH: a compact soft x-ray spectrometer operating at Elettra

    SciTech Connect

    Cocco, Daniele; Matteucci, Maurizio; Zangrando, Marco; Bondino, Federica; Zacchigna, Michele; Plate, Mauro; Parmigiani, Fulvio; Nelles, Bruno; Prince, Kevin C.

    2004-05-12

    To accommodate increasing interest in soft x-ray inelastic scattering, a new spectrometer has been designed, constructed and commissioned at Elettra. This instrument uses as the dispersive element one of two interchangeable Variable Line Spacing (VLS) spherical gratings. The energy scan is performed by a 7 cm linear translation of a back illuminated CCD which also collects the zero order light, facilitating alignment and calibration. The two gratings have the same radius of curvature while the groove densities and the groove density variations differ by a factor four. Thus the energies focused by the gratings at a particular position differ by a factor of four. The total length of the instrument is 60 cm, the energy range covered is roughly 25-1000 eV and the expected resolving power ranges from 1000 to 5000. The spectrometer is now operating on the beamline Bach. It takes advantage of the small size of the photon spot in the experimental chamber and of the possibility to control the polarization of the incoming radiation. The small spot constitutes the virtual entrance slit, and the spectrometer collects the photons emitted in a solid angle of about 30x10 mrad2. The instrument, named ComIXS (Compact Inelastic X-ray Spectrometer), has been routinely operating since October 2002. Several experiments have already been carried out, and some results illustrating the characteristics of the instrument are described. The manufacture and testing of the blaze gratings are also discussed.

  2. ComIXS on BACH: a compact soft x-ray spectrometer operating at Elettra

    NASA Astrophysics Data System (ADS)

    Cocco, Daniele; Zangrando, Marco; Matteucci, Maurizio; Bondino, Federica; Platè, Mauro; Zacchigna, Michele; Parmigiani, Fulvio; Nelles, Bruno; Prince, Kevin C.

    2004-05-01

    To accommodate increasing interest in soft x-ray inelastic scattering, a new spectrometer has been designed, constructed and commissioned at Elettra. This instrument uses as the dispersive element one of two interchangeable Variable Line Spacing (VLS) spherical gratings. The energy scan is performed by a 7 cm linear translation of a back illuminated CCD which also collects the zero order light, facilitating alignment and calibration. The two gratings have the same radius of curvature while the groove densities and the groove density variations differ by a factor four. Thus the energies focused by the gratings at a particular position differ by a factor of four. The total length of the instrument is 60 cm, the energy range covered is roughly 25-1000 eV and the expected resolving power ranges from 1000 to 5000. The spectrometer is now operating on the beamline Bach. It takes advantage of the small size of the photon spot in the experimental chamber and of the possibility to control the polarization of the incoming radiation. The small spot constitutes the virtual entrance slit, and the spectrometer collects the photons emitted in a solid angle of about 30×10 mrad2. The instrument, named ComIXS (Compact Inelastic X-ray Spectrometer), has been routinely operating since October 2002. Several experiments have already been carried out, and some results illustrating the characteristics of the instrument are described. The manufacture and testing of the blaze gratings are also discussed.

  3. Description of the Earth in the Works of Arabic Geographers from IX to XII Century

    NASA Astrophysics Data System (ADS)

    Cvijanovic, I.

    2012-12-01

    The works of Arabic writers provide data about shape, position and size of the Earth, planets and zodiac signs. They include preserved maps of Ibn Haukal, Al-Masudi and Al-Idrisi. Al-Masudi (871-956/7) made a map of the world and wrote that the Earth is round, before the Christians in Europe were ready to accept that idea. The famous geographer and cartographer Al-Idrisi (IX/X., died in 903/913.) has lived on the court of Norman king Roger II of Sicily, and after his death on the court of his son William I on Sicily, where he obtained the data from European and Arabic geographers. On the basis of this data he wrote a work known entitled Roger's book. Besides this important work he made a celestial globe and a map of the world in the shape of a silver disk. The lines that marked the borders of seven regions of the inhabited world were engraved on this disk. The Arabs had excellent knowledge of Greek astronomy and accepted their division of the world in seven climatic zones.

  4. Ares I and Ares I-X Stage Separation Aerodynamic Testing

    NASA Technical Reports Server (NTRS)

    Pinier, Jeremy T.; Niskey, Charles J.

    2011-01-01

    The aerodynamics of the Ares I crew launch vehicle (CLV) and Ares I-X flight test vehicle (FTV) during stage separation was characterized by testing 1%-scale models at the Arnold Engineering Development Center s (AEDC) von Karman Gas Dynamics Facility (VKF) Tunnel A at Mach numbers of 4.5 and 5.5. To fill a large matrix of data points in an efficient manner, an injection system supported the upper stage and a captive trajectory system (CTS) was utilized as a support system for the first stage located downstream of the upper stage. In an overall extremely successful test, this complex experimental setup associated with advanced postprocessing of the wind tunnel data has enabled the construction of a multi-dimensional aerodynamic database for the analysis and simulation of the critical phase of stage separation at high supersonic Mach numbers. Additionally, an extensive set of data from repeated wind tunnel runs was gathered purposefully to ensure that the experimental uncertainty would be accurately quantified in this type of flow where few historical data is available for comparison on this type of vehicle and where Reynolds-averaged Navier-Stokes (RANS) computational simulations remain far from being a reliable source of static aerodynamic data.

  5. Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study.

    PubMed

    Asghari-Khiavi, Mehdi; Vongsvivut, Jitraporn; Perepichka, Inna; Mechler, Adam; Wood, Bayden R; McNaughton, Don; Bohle, D Scott

    2011-12-01

    To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine-FP complex is not μ-oxo dimeric indicating that the hypothesis that chloroquine binds to FP μ-oxo dimer with a stoichiometry of 1 chloroquine:2 μ-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine. Raman spectroscopy data does not provide any evidence to support the formation of a similar salt bridge in the complexes of FP with quinine and mefloquine; however, it suggests that the interaction of these drugs with FP happens through coordination of the Fe(III) center of the porphyrin to the 9-hydroxy group of the drug.

  6. Initial Operation of the PhIX High Intensity Plasma Source

    NASA Astrophysics Data System (ADS)

    Caughman, J. B. O.; Goulding, R. H.; Biewer, T. M.; Bigelow, T. S.; Diem, S. J.; Pesavento, P. V.; Rapp, J.; Shaw, G. C.

    2013-10-01

    The Physics Integration eXperiment (PhIX) is a linear high-intensity rf plasma source that combines a high-density helicon plasma generator with an electron heating section. It is being used to study the physics of heating over-dense plasmas in a linear configuration, as well as exploring source interactions with a downstream target. The helicon plasma is produced by coupling 13.56 MHz rf power at levels up to 100 kW. Microwaves at 18 GHz are coupled to the electrons in the over-dense helicon plasma via whistler waves and Electron Bernstein Waves (EBW). An energy analyzer embedded in the target substrate is being used to determine the ion energy and ion flux at the target, while a microwave interferometer and Langmuir probes are used to determine plasma parameters near the source and near the target. High plasma densities have been produced in He (>5 × 1019/m3) and H (>1.5 × 1019/m3) , and operation in magnetic field strengths up to 0.5T has been demonstrated. Details of the experimental results will be presented, as well as future plans for studying plasma surface interactions and rf antenna plasma interactions. ORNL is managed by UT-Battelle, LLC, for the U.S. DOE under contract DE-AC-05-00OR22725.

  7. Danazol increases factor VIII and factor IX in classic hemophilia and Christmas disease.

    PubMed

    Gralnick, H R; Rick, M E

    1983-06-01

    We gave danazol (600 mg per day orally for 14 days), an attenuated androgen, to four adults with classic hemophilia and one adult with Christmas disease. The levels of factor VIII in the patients with classic hemophilia ranged from 1 to 3 per cent before treatment and rose to 3 to 8 per cent during the treatment period. The level of factor IX in the patient with Christmas disease rose from 5 to 14 per cent. The rise in clotting-factor activity was usually observed within five to six days after the initiation of therapy and peaked between 7 and 13 days. The drug had no untoward effects. During the 70 patient-days of therapy, only two patients required plasma products, each on one occasion. These data suggest that danazol therapy may decrease the hemorrhagic tendency and reduce the need for transfusions of plasma products in classic hemophilia and Christmas disease. Controlled clinical trials will be required to establish its value in these applications.

  8. Dynamics of gravitating hadron matter in a Bianchi-IX cosmological model

    NASA Astrophysics Data System (ADS)

    Pavluchenko, Sergey A.

    2016-08-01

    We perform an analysis of the Einstein-Skyrme cosmological model in the Bianchi-IX background. We analytically describe asymptotic regimes and semianalytically describe generic regimes. It appears that depending on the product of the Newtonian constant κ with Skyrme coupling K , in the absence of the cosmological term, there are three possible regimes: recollapse with κ K <2 and two power-law regimes, ∝t1 /2 for κ K =2 and ∝t for κ K >2 . In the presence of the positive cosmological term, power-law regimes turn to the exponential (de Sitter) ones, while the recollapse regime turns to the exponential if the value for the Λ -term is sufficiently large, otherwise the regime remains recollapse. The negative cosmological term leads to the recollapse regardless of κ K . All nonsingular regimes have the squashing coefficient a (t )→1 at late times, which is associated with restoring symmetry dynamics. Also all nonsingular regimes appear to be linearly stable exponential solutions always, while power-law regimes for an open region of the initial conditions.

  9. Licenced to pollute but not to poison: The ineffectiveness of regulatory authorities at protecting public health from atmospheric arsenic, lead and other contaminants resulting from mining and smelting operations

    NASA Astrophysics Data System (ADS)

    Taylor, Mark Patrick; Davies, Peter J.; Kristensen, Louise Jane; Csavina, Janae Lynn

    2014-09-01

    This article details and examines the impact of significant inconsistencies in pollution licencing, monitoring and reporting from Australia’s leading mining and smelting communities of Mount Isa in Queensland and Port Pirie in South Australia. Although emissions to the environment are regulated according to Australia’s national air quality standards, significant atmospheric point source toxic emissions of arsenic, lead and sulfur dioxide continue to contaminate Mount Isa and Port Pirie communities. Short-term atmospheric contaminant emissions across residential areas from the Mount Isa Mines operations are significant: in 2011, 24-h maximum suspended particulate (TSP) values for lead-in-air and arsenic-in-air were 12.8 μg/m3 and 2973 ng/m3, respectively. The relevant Queensland air quality objectives for lead and arsenic are 0.5 μg/m3 (TSP) and 6 ng/m3 (PM10), respectively, averaged over a year. Mount Isa is also blanketed by elevated sulfur dioxide concentrations, with the Australian and Queensland 1-h air quality standard (0.2 ppm) being exceeded on 27 occasions in 2011. At Port Pirie, contamination of the urban environment is arguably worse with 24-h maximum TSP values for lead-in-air and arsenic-in-air of 22.57 μg/m3 (2011) and 250 ng/m3 (2009), respectively. Port Pirie has an annual average lead-in-air standard of 0.5 μg/m3 (TSP) but there are no set values for arsenic. In 2012, the national 1-h standard for sulfur dioxide was exceeded 50 times in Port Pirie. Despite chronic childhood blood lead exposures in both communities, there is a history of denial and downplaying of the source and impact of the contamination. A contributory factor to this pattern of behaviour is the fragmented and inconsistent delivery of data as well as its interpretation in relation to environmental and health impacts from exposures. This study reviews available data sources and makes inference to the impacts from contamination and in doing so, explains why the current

  10. Synthesis and separation by thin-layer chromatography of bilirubin-IX isomers. Their identification as tetrapyrroles and dipyrrolic ethyl anthranilate azo derivatives.

    PubMed Central

    Blanckaert, N; Heirwegh, K P; Compernolle, F

    1976-01-01

    Procedures for the synthesis, separation and determination of structure of the bilirubin-IX isomers are described. 1. The four biliverdin-IX isomers were prepared by oxidative cleavage of haemin and were separated as their dimethyl esters. The individual esters were reduced with NaBH4, and the bilirubin esters obtained were subjected to alkaline hydrolysis yielding the corresponding bilirubin-IX isomers. 2. The bilirubin-IX isomers were structurally characterized (a) at the tetrapyrrolic stage by mass spectrometry of their trimethylsilyl derivatives and (b) by formation and structural analysis of their dipyrrolic ethyl anthranilate azo derivatives. 3. The absorption spectrum of bilirubin-IX alpha differed strikingly from the spectra of the other isomers. The presence of a pronounced shoulder around 453 nm in the spectrum of bilirubin-IXbeta allows easy differentiation from bilirubin-IXdelta. Methylation of the carboxyl groups largely eliminates the spectral differences between the IXalpha- and non-alpha isomers. 4. The bilirubin-IX isomers are conveniently separated by t.l.c. Detection and unequivocal identification is possible on a micro-scale by (a) t.l.c. with respect to reference compounds and (b) subsequent formation and t.l.c. of the more stable ethyl anthranilate azopigments. 5. Pronounced differences in polarity, i.e. solvent distribution, between the bilirubin-IX isomers indicate that a re-evaluation of conclusions reached previously with regard to the presence in, or absence from, biological fluids of some isomers and their relative amounts is needed. PMID:938489

  11. Research and Evaluations of the Health Aspects of Disasters, Part IX: Risk-Reduction Framework.

    PubMed

    Birnbaum, Marvin L; Daily, Elaine K; O'Rourke, Ann P; Loretti, Alessandro

    2016-06-01

    A disaster is a failure of resilience to an event. Mitigating the risks that a hazard will progress into a destructive event, or increasing the resilience of a society-at-risk, requires careful analysis, planning, and execution. The Disaster Logic Model (DLM) is used to define the value (effects, costs, and outcome(s)), impacts, and benefits of interventions directed at risk reduction. A Risk-Reduction Framework, based on the DLM, details the processes involved in hazard mitigation and/or capacity-building interventions to augment the resilience of a community or to decrease the risk that a secondary event will develop. This Framework provides the structure to systematically undertake and evaluate risk-reduction interventions. It applies to all interventions aimed at hazard mitigation and/or increasing the absorbing, buffering, or response capacities of a community-at-risk for a primary or secondary event that could result in a disaster. The Framework utilizes the structure provided by the DLM and consists of 14 steps: (1) hazards and risks identification; (2) historical perspectives and predictions; (3) selection of hazard(s) to address; (4) selection of appropriate indicators; (5) identification of current resilience standards and benchmarks; (6) assessment of the current resilience status; (7) identification of resilience needs; (8) strategic planning; (9) selection of an appropriate intervention; (10) operational planning; (11) implementation; (12) assessments of outputs; (13) synthesis; and (14) feedback. Each of these steps is a transformation process that is described in detail. Emphasis is placed on the role of Coordination and Control during planning, implementation of risk-reduction/capacity building interventions, and evaluation. Birnbaum ML , Daily EK , O'Rourke AP , Loretti A . Research and evaluations of the health aspects of disasters, part IX: Risk-Reduction Framework. Prehosp Disaster Med. 2016;31(3):309-325. PMID:27033777

  12. Identification of an iridium-containing compound with a formal oxidation state of IX.

    PubMed

    Wang, Guanjun; Zhou, Mingfei; Goettel, James T; Schrobilgen, Gary J; Su, Jing; Li, Jun; Schlöder, Tobias; Riedel, Sebastian

    2014-10-23

    One of the most important classifications in chemistry and within the periodic table is the concept of formal oxidation states. The preparation and characterization of compounds containing elements with unusual oxidation states is of great interest to chemists. The highest experimentally known formal oxidation state of any chemical element is at present VIII, although higher oxidation states have been postulated. Compounds with oxidation state VIII include several xenon compounds (for example XeO4 and XeO3F2) and the well-characterized species RuO4 and OsO4 (refs 2-4). Iridium, which has nine valence electrons, is predicted to have the greatest chance of being oxidized beyond the VIII oxidation state. In recent matrix-isolation experiments, the IrO4 molecule was characterized as an isolated molecule in rare-gas matrices. The valence electron configuration of iridium in IrO4 is 5d(1), with a formal oxidation state of VIII. Removal of the remaining d electron from IrO4 would lead to the iridium tetroxide cation ([IrO4](+)), which was recently predicted to be stable and in which iridium is in a formal oxidation state of IX. There has been some speculation about the formation of [IrO4](+) species, but these experimental observations have not been structurally confirmed. Here we report the formation of [IrO4](+) and its identification by infrared photodissociation spectroscopy. Quantum-chemical calculations were carried out at the highest level of theory that is available today, and predict that the iridium tetroxide cation, with a Td-symmetrical structure and a d(0) electron configuration, is the most stable of all possible [IrO4](+) isomers. PMID:25341786

  13. Identification of an iridium-containing compound with a formal oxidation state of IX

    NASA Astrophysics Data System (ADS)

    Wang, Guanjun; Zhou, Mingfei; Goettel, James T.; Schrobilgen, Gary J.; Su, Jing; Li, Jun; Schlöder, Tobias; Riedel, Sebastian

    2014-10-01

    One of the most important classifications in chemistry and within the periodic table is the concept of formal oxidation states. The preparation and characterization of compounds containing elements with unusual oxidation states is of great interest to chemists. The highest experimentally known formal oxidation state of any chemical element is at present VIII, although higher oxidation states have been postulated. Compounds with oxidation state VIII include several xenon compounds (for example XeO4 and XeO3F2) and the well-characterized species RuO4 and OsO4 (refs 2, 3, 4). Iridium, which has nine valence electrons, is predicted to have the greatest chance of being oxidized beyond the VIII oxidation state. In recent matrix-isolation experiments, the IrO4 molecule was characterized as an isolated molecule in rare-gas matrices. The valence electron configuration of iridium in IrO4 is 5d1, with a formal oxidation state of VIII. Removal of the remaining d electron from IrO4 would lead to the iridium tetroxide cation ([IrO4]+), which was recently predicted to be stable and in which iridium is in a formal oxidation state of IX. There has been some speculation about the formation of [IrO4]+ species, but these experimental observations have not been structurally confirmed. Here we report the formation of [IrO4]+ and its identification by infrared photodissociation spectroscopy. Quantum-chemical calculations were carried out at the highest level of theory that is available today, and predict that the iridium tetroxide cation, with a Td-symmetrical structure and a d0 electron configuration, is the most stable of all possible [IrO4]+ isomers.

  14. Fluorescence imaging and spectroscopy of ALA-induced protoporphyrin IX preferentially accumulated in tumor tissue

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Beyer, Wolfgang; Knuechel, Ruth; Koerner, T. O.; Kriegmair, M.; Rick, Kai; Steinbach, Pia; Hofstetter, Alfons G.

    1995-12-01

    In a clinical pilot study performed on 104 patients suffering from bladder cancer it could be shown that intravesical instillation of a solution of 5-aminolevulinic acid (5-ALA) induces a tumorselective accumulation of Protoporphyrin IX (PPIX). Malignant lesions could be detected with a sensitivity of 97% and a specificity of 67%. The Kr+-laser as excitation light source could successfully be replaced by a filtered short arc Xe-lamp. Its emission wavelength band (375 nm - 440 nm) leads to an efficiency of 58% for PPIX- excitation compared to the laser. Two-hundred-sixty mW of output power at the distal end of a slightly modified cystoscope could be obtained. This is sufficient for recording fluorescence images with a target integrating color CCD-camera. Red fluorescence and blue remitted light are displayed simultaneously. Standard white light observation is possible with the same instrumentation. Pharmacokinetic measurements were performed on 18 patients after different routes of 5-ALA application (oral, inhalation and intravesical instillation). PPIX-fluorescence measurements were made on the skin and on the blood plasma. Pharmacokinetic of 5-ALA could be performed on blood plasma. Endoscopical florescence spectroscopy showed the high fluorescence contrast between tumor and normal tissue with a mean value of 10.7. Forthcoming clinical multicenter studies require an objective measure of the fluorescence intensity. Monte Carlo computer simulations showed that artifacts due to observation geometry and varying absorption can largely be reduced by ratioing fluorescence (red channel of camera) to remission (blue channel). Real time image ratioing provides false color images with a reliable fluorescence information.

  15. Ares I-X Flight Test Validation of Control Design Tools in the Frequency-Domain

    NASA Technical Reports Server (NTRS)

    Johnson, Matthew; Hannan, Mike; Brandon, Jay; Derry, Stephen

    2011-01-01

    A major motivation of the Ares I-X flight test program was to Design for Data, in order to maximize the usefulness of the data recorded in support of Ares I modeling and validation of design and analysis tools. The Design for Data effort was intended to enable good post-flight characterizations of the flight control system, the vehicle structural dynamics, and also the aerodynamic characteristics of the vehicle. To extract the necessary data from the system during flight, a set of small predetermined Programmed Test Inputs (PTIs) was injected directly into the TVC signal. These PTIs were designed to excite the necessary vehicle dynamics while exhibiting a minimal impact on loads. The method is similar to common approaches in aircraft flight test programs, but with unique launch vehicle challenges due to rapidly changing states, short duration of flight, a tight flight envelope, and an inability to repeat any test. This paper documents the validation effort of the stability analysis tools to the flight data which was performed by comparing the post-flight calculated frequency response of the vehicle to the frequency response calculated by the stability analysis tools used to design and analyze the preflight models during the control design effort. The comparison between flight day frequency response and stability tool analysis for flight of the simulated vehicle shows good agreement and provides a high level of confidence in the stability analysis tools for use in any future program. This is true for both a nominal model as well as for dispersed analysis, which shows that the flight day frequency response is enveloped by the vehicle s preflight uncertainty models.

  16. Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro and In Vivo

    PubMed Central

    Zigrino, Addolorata; Leo, Valentina; Renna, Giuseppe; Montagnani, Monica

    2013-01-01

    Granisetron is a 5-HT3 receptors antagonist used in the management of emesis associated with anticancer chemotherapy. It affects intestinal motility with constipating effect. Since the pathway heme oxygenase/carbon monoxide (HO/CO) is involved in gastrointestinal motility, we evaluated the possible interplay between granisetron and agents affecting HO/CO pathways such as zinc protoporphyrin IX (ZnPPIX), an HO inhibitor, or hemin, an HO-1 inducer. ZnPPIX (10 µM) or hemin (10 µM), but not granisetron (0.1, 0.3, 1 µM), affected spontaneous basal activity recorded in rat duodenal strips, in noncholinergic nonadrenergic conditions. Granisetron restored spontaneous basal activity after ZnPPIX, but not after hemin. ZnPPIX decreased and hemin increased the inhibition of activity after electrical field stimulation (EFS), but they did not affect the contraction that follows the relaxation induced by EFS called off contraction. Granisetron did not alter the response to EFS per se but abolished both ZnPPIX and hemin effect when coadministered. In vivo study showed constipating effect of granisetron (25, 50, 75 µg/kg/sc) but no effect of either ZnPPIX (50 µg/kg/i.p.) or hemin (50 µM/kg/i.p.). When coadministered, granisetron effect was abolished by ZnPPIX and increased by hemin. Specimens from rats treated in vivo with hemin (50 µM/kg/i.p.) showed increased HO-1 protein levels. In conclusion, granisetron seems to interact with agents affecting HO/CO pathway both in vitro and in vivo. PMID:23864955

  17. Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

    PubMed

    Anderson, C D; Moisyadi, S; Avelar, A; Walton, C B; Shohet, R V

    2016-06-01

    Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

  18. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

    PubMed Central

    Arivett, Brock A.; Fiester, Steven E.; Ohneck, Emily J.; Penwell, William F.; Kaufman, Cynthia M.; Relich, Ryan F.

    2015-01-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606T and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606T and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606T or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media. PMID:26416873

  19. Torino 2006. XX Olympic and IX Paralympic Winter Games: the ENT experience

    PubMed Central

    Succo, G; Crosetti, E; Mattiazzo, A; Riontino, E; Massazza, G

    2008-01-01

    Summary A total of 27 competition days, more than 3000 athletes, over 10,000 components of the Olympic family, 3,500 workers, 2,500 volunteers, an overall business of more than 2 billion Euros. These, in a nutshell, are just a few of the data concerning the XX Olympic and the IX Paralympic Winter Games, Torino, Italy, 2006. Such a huge event, obviously required a meticulously organized medical service to cope with the healthcare of the athletes, official workers and the Olympic family, distributed over a geographic area of approximately 80 km in diameter. An ENT service was organized within the medical service, which was divided between 3 Polyclinics, in which 12 ENT Specialists were on duty. The present report gives an account of the final data concerning the service involved, together with a description of the approach used in the actual organization, with a view to providing useful information for colleagues who will be called upon, for a similar service, in future Olympic Winter Games. The ENT healthcare offered was confirmed to be proportional to the requirements, both from a qualitative and quantitative point of view. All the ENT specialists involved, reported having gained an immense store of human experience from having lived the Olympic atmosphere as a volunteer exerting one’s own profession. The facilities available in the Polyclinics, which were at a considerable distance from the Hospital, were found to be more than adequate with respect to the pathological conditions and service requested, particularly in 17% of the cases which would otherwise have been sent to a Hospital Outpatient Unit at least 80 km away. PMID:18646571

  20. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes.

    PubMed

    Arivett, Brock A; Fiester, Steven E; Ohneck, Emily J; Penwell, William F; Kaufman, Cynthia M; Relich, Ryan F; Actis, Luis A

    2015-12-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.

  1. Accumulation of functional recombinant human coagulation factor IX in transgenic soybean seeds.

    PubMed

    Cunha, Nicolau B; Murad, André M; Ramos, Gustavo L; Maranhão, Andréia Q; Brígido, Marcelo M; Araújo, Ana Cláudia G; Lacorte, Cristiano; Aragão, Francisco J L; Covas, Dimas T; Fontes, Aparecida M; Souza, Gustavo H M F; Vianna, Giovanni R; Rech, Elíbio L

    2011-08-01

    The seed-based production of recombinant proteins is an efficient strategy to achieve the accumulation, correct folding, and increased stability of these recombinant proteins. Among potential plant molecular farming systems, soybean [Glycine max (L.) Merrill] is a viable option for the production of recombinant proteins due to its high protein content, known regulatory sequences, efficient gene transfer protocols, and a scalable production system under greenhouse conditions. We report here the expression and stable accumulation of human coagulation factor IX (hFIX) in transgenic soybean seeds. A biolistic process was utilised to co-introduce a plasmid carrying the hFIX gene under the transcriptional control of the α' subunit of a β-conglycinin seed-specific promoter and an α-Coixin signal peptide in soybean embryonic axes from mature seeds. The 56-kDa hFIX protein was expressed in the transgenic seeds at levels of up to 0.23% (0.8 g kg(-1) seed) of the total soluble seed protein as determined by an enzyme-linked immunosorbent assay (ELISA) and western blot. Ultrastructural immunocytochemistry assays indicated that the recombinant hFIX in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Mass spectrometry characterisation confirmed the presence of the hFIX recombinant protein sequence. Protein extracts from transgenic seeds showed a blood-clotting activity of up to 1.4% of normal plasma. Our results demonstrate the correct processing and stable accumulation of functional hFIX in soybean seeds stored for 6 years under room temperature conditions (22 ± 2°C).

  2. In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

    PubMed

    Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

    2016-07-01

    N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. PMID:27356208

  3. Trajectory-Based Loads for the Ares I-X Test Flight Vehicle

    NASA Technical Reports Server (NTRS)

    Vause, Roland F.; Starr, Brett R.

    2011-01-01

    In trajectory-based loads, the structural engineer treats each point on the trajectory as a load case. Distributed aero, inertial, and propulsion forces are developed for the structural model which are equivalent to the integrated values of the trajectory model. Free-body diagrams are then used to solve for the internal forces, or loads, that keep the applied aero, inertial, and propulsion forces in dynamic equilibrium. There are several advantages to using trajectory-based loads. First, consistency is maintained between the integrated equilibrium equations of the trajectory analysis and the distributed equilibrium equations of the structural analysis. Second, the structural loads equations are tied to the uncertainty model for the trajectory systems analysis model. Atmosphere, aero, propulsion, mass property, and controls uncertainty models all feed into the dispersions that are generated for the trajectory systems analysis model. Changes in any of these input models will affect structural loads response. The trajectory systems model manages these inputs as well as the output from the structural model over thousands of dispersed cases. Large structural models with hundreds of thousands of degrees of freedom would execute too slowly to be an efficient part of several thousand system analyses. Trajectory-based loads provide a means for the structures discipline to be included in the integrated systems analysis. Successful applications of trajectory-based loads methods for the Ares I-X vehicle are covered in this paper. Preliminary design loads were based on 2000 trajectories using Monte Carlo dispersions. Range safety loads were tied to 8423 malfunction turn trajectories. In addition, active control system loads were based on 2000 preflight trajectories using Monte Carlo dispersions.

  4. Involvement of the Type IX Secretion System in Capnocytophaga ochracea Gliding Motility and Biofilm Formation

    PubMed Central

    Kita, Daichi; Shibata, Satoshi; Kikuchi, Yuichiro; Kokubu, Eitoyo; Nakayama, Koji; Saito, Atsushi

    2016-01-01

    Capnocytophaga ochracea is a Gram-negative, rod-shaped bacterium that demonstrates gliding motility when cultured on solid agar surfaces. C. ochracea possesses the ability to form biofilms; however, factors involved in biofilm formation by this bacterium are unclear. A type IX secretion system (T9SS) in Flavobacterium johnsoniae was shown to be involved in the transport of proteins (e.g., several adhesins) to the cell surface. Genes orthologous to those encoding T9SS proteins in F. johnsoniae have been identified in the genome of C. ochracea; therefore, the T9SS may be involved in biofilm formation by C. ochracea. Here we constructed three ortholog-deficient C. ochracea mutants lacking sprB (which encodes a gliding motility adhesin) or gldK or sprT (which encode T9SS proteins in F. johnsoniae). Gliding motility was lost in each mutant, suggesting that, in C. ochracea, the proteins encoded by sprB, gldK, and sprT are necessary for gliding motility, and SprB is transported to the cell surface by the T9SS. For the ΔgldK, ΔsprT, and ΔsprB strains, the amounts of crystal violet-associated biofilm, relative to wild-type values, were 49%, 34%, and 65%, respectively, at 48 h. Confocal laser scanning and scanning electron microscopy revealed that the biofilms formed by wild-type C. ochracea were denser and bacterial cells were closer together than in those formed by the mutant strains. Together, these results indicate that proteins exported by the T9SS are key elements of the gliding motility and biofilm formation of C. ochracea. PMID:26729712

  5. Pilot production of recombinant human clotting factor IX from transgenic sow milk.

    PubMed

    Sun, Yu-ling; Chang, Yuo-sheng; Lin, Yin-shen; Yen, Chon-ho

    2012-06-01

    Valuable pharmaceutical proteins produced from the mammary glands of transgenic livestock have potential use in the biomedical industry. In this study, recombinant human clotting factor IX (rhFIX) produced from transgenic sow milk for preclinical animal studies have been established. The transgenic sow milk was skimmed and treated with sodium phosphate buffer to remove abundant casein protein. Then, the γ-carboxylated rhFIX fraction was segregated through the Q Sepharose chromatography from uncarboxylated one. For safety issue, the process included virus inactivation by solvent/detergent (S/D) treatment. Subsequently, the S/D treated sample was loaded into the Heparin Sepharose column to recover the rhFIX fraction, which was then reapplied to the Heparin Sepharose column to enhance rhFIX purity and lower the ratio of activated form rhFIX (rhFIXa) easily. This was possible due to the higher affinity of the Heparin affinity sorbent for rhFIXa than for the rhFIX zymogen. Furthermore, an IgA removal column was used to eliminate porcine IgA in purified rhFIX. Finally, nanofiltration was performed for viral clearance. Consequently, a high-quality rhFIX product was produced (approximately 700 mg per batch). Other values for final rhFIX preparation were as follows: purity, >99%; average specific activity, 415.6±57.7 IU/mL and total milk impurity, <0.5 ng/mg. This is the first report that described the whole process and stable production of bioactive rhFIX from transgenic sow milk. The overall manufacturing process presented here has the potential for industrial production of rhFIX for treatment of hemophilia B patients.

  6. Optical properties of Ge-rich G e1 -xS ix alloys: Compositional dependence of the lowest direct and indirect gaps

    NASA Astrophysics Data System (ADS)

    Xu, Chi; Gallagher, J. D.; Senaratne, C. L.; Menéndez, J.; Kouvetakis, J.

    2016-03-01

    Ge-rich G e1 -xS ix alloys have been investigated using spectroscopic ellipsometry and photoluminescence at room temperature. Special emphasis was placed on the compositional dependence of the lowest-energy interband transitions. For x ≤0.05 , a compositional range of particular interest for modern applications, we find E0=0.799 (1 ) +3.214 (45 ) x +0.080 (44 ) x2 (in eV) for the lowest direct gap. The compositional dependence of the indirect gap is obtained from photoluminescence as Eind=0.659 (4 ) +1.18 (17 ) x (in eV). We find no significant discrepancies between these results and the extrapolations from measurements at higher Si concentrations. Such discrepancies had been suggested by recent work on G e1 -xS ix films on Si. Accurate knowledge of the interband transition energies is an important requirement for the design of devices incorporating Ge-rich G e1 -xS ix alloys and for the understanding of more complex systems, such as ternary G e1 -x -yS ixS ny alloys, in terms of its binary constituents.

  7. 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.

  8. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B

    SciTech Connect

    Thompson, A.R. Puget Sound Blood Center, Seattle, WA ); Darlington, G. ); Armentano, D.; Woo, S.L.C.

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. The authors report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently {gamma}-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  9. Combination of Protoporphyrin IX-mediated Sonodynamic Treatment with Doxorubicin Synergistically Induced Apoptotic Cell Death of a Multidrug-Resistant Leukemia K562/DOX Cell Line.

    PubMed

    Wang, Xiaobing; Jia, Yali; Su, Xiaomin; Wang, Pan; Zhang, Kun; Feng, Xiaolan; Liu, Quanhong

    2015-10-01

    The main objective of this study was to evaluate the efficacy of administration of doxorubicin (DOX) in combination with protoporphyrin IX (PpIX)-assisted low-level therapeutic ultrasound (US) in K562/DOX cells as a potential strategy in cancer therapy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the cytotoxicity of different treatments. Apoptosis was analyzed using annexin V-PE/7-amino-actinomycin D staining. Changes in DNA fragmentation, intracellular reactive oxygen species production, cellular membrane permeability, P-glycoprotein expression and DOX uptake were analyzed with flow cytometry. Under optimal conditions, PpIX-US significantly aggravated DOX-induced K562/DOX cell death, compared with either monotherapy. Synergistic potentiation of DNA damage, generation of reactive oxygen species and P-glycoprotein inhibition were observed. Plasma membrane integrity changed slightly after US exposure, and DOX uptake was notably improved after PpIX-US exposure. The results indicate that PpIX-US could increase the susceptibility of tumors to antineoplastic drugs, suggesting a clinical potential method for sonodynamic therapy-mediated tumor chemotherapy. PMID:26166458

  10. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    PubMed Central

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J.T.

    2013-01-01

    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. PMID:23585459

  11. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: potential for gene therapy of hemophilia B.

    PubMed

    Armentano, D; Thompson, A R; Darlington, G; Woo, S L

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. We report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently gamma-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  12. Molecular Phylogeny and Intricate Evolutionary History of the Three Isofunctional Enzymes Involved in the Oxidation of Protoporphyrinogen IX

    PubMed Central

    Kobayashi, Koichi; Masuda, Tatsuru; Tajima, Naoyuki; Wada, Hajime; Sato, Naoki

    2014-01-01

    Tetrapyrroles such as heme and chlorophyll are essential for biological processes, including oxygenation, respiration, and photosynthesis. In the tetrapyrrole biosynthesis pathway, protoporphyrinogen IX oxidase (Protox) catalyzes the formation of protoporphyrin IX, the last common intermediate for the biosynthesis of heme and chlorophyll. Three nonhomologous isofunctional enzymes, HemG, HemJ, and HemY, for Protox have been identified. To reveal the distribution and evolution of the three Protox enzymes, we identified homologs of each along with other heme biosynthetic enzymes by whole-genome clustering across three domains of life. Most organisms possess only one of the three Protox types, with some exceptions. Detailed phylogenetic analysis revealed that HemG is mostly limited to γ-Proteobacteria whereas HemJ may have originated within α-Proteobacteria and transferred to other Proteobacteria and Cyanobacteria. In contrast, HemY is ubiquitous in prokaryotes and is the only Protox in eukaryotes, so this type may be the ancestral Protox. Land plants have a unique HemY homolog that is also shared by Chloroflexus species, in addition to the main HemY homolog originating from Cyanobacteria. Meanwhile, organisms missing any Protox can be classified into two groups; those lacking most heme synthetic genes, which necessarily depend on external heme supply, and those lacking only genes involved in the conversion of uroporphyrinogen III into heme, which would use a precorrin2-dependent alternative pathway. However, hemN encoding coproporphyrinogen IX oxidase was frequently found in organisms lacking Protox enzyme, which suggests a unique role of this gene other than in heme biosynthesis. PMID:25108393

  13. Oro-facial-digital syndrome IX with severe microcephaly: a new variant in a genetically isolated population.

    PubMed

    Erickson, Robert P; Bodensteiner, John B

    2007-12-15

    We describe four patients, two pairs of siblings, with a somewhat unique oro-facial-digital syndrome. The siblings come from the Navajo population which has undergone several genetic "bottlenecks." Thus, as would be anticipated, this syndrome seems to show autosomal recessive inheritance. The combination of the presence of retinal colobomata and the paucity of digital findings in these patients leads us to believe that their condition is best described as a variant of oro-facial-digital syndrome IX. In addition to retinal colobomata, these patients also show severe microcephaly, mental retardation and short stature. PMID:18000902

  14. VizieR Online Data Catalog: MYStIX: the Chandra X-ray sources (Kuhn+, 2013)

    NASA Astrophysics Data System (ADS)

    Kuhn, M. A.; Getman, K. V.; Broos, P. S.; Townsley, L. K.; Feigelson, E. D.

    2013-11-01

    X-ray observations were made with the imaging array on the Advanced CCD Imaging Spectrometer (ACIS-I) on board the Chandra X-Ray Observatory. This array of four CCD detectors subtends 17'x17' on the sky. Data were acquired from the Chandra Data Archive from 2001 Jan to Mar 2008 for 10 MYStIX fields (Flame Nebula, RCW 36, NGC 2264, Rosette Nebula, Lagoon Nebula, NGC 2362, DR 21, RCW 38, Trifid Nebula and NGC 1893); see table1. (2 data files).

  15. Carbonic anhydrase inhibitors: benzenesulfonamides incorporating cyanoacrylamide moieties are low nanomolar/subnanomolar inhibitors of the tumor-associated isoforms IX and XII.

    PubMed

    Alafeefy, Ahmed M; Isik, Semra; Abdel-Aziz, Hatem A; Ashour, Abdelkader E; Vullo, Daniela; Al-Jaber, Nabila A; Supuran, Claudiu T

    2013-03-15

    A series of benzenesulfonamides incorporating cyanoacrylamide moieties (tyrphostine analogues) have been obtained by reaction of sulfanilamide with ethylcyanoacetate followed by condensation with aromatic/heterocyclic aldehydes, isothiocyanates or diazonium salts. The new compounds have been investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4. 2.1.1), and more specifically against the cytosolic human (h) isoforms hCA I and II, as well as the transmembrane, tumor-associated ones CA IX and XII, which are validated antitumor targets. Most of the new benzenesulfonamides were low nanomolar or subnanomolar CA IX/XII inhibitors whereas they were less effective as inhibitors of CA I and II. The structure-activity relationship for this class of effective CA inhibitors is also discussed. Generally, electron donating groups in the starting aldehyde reagent favored CA IX and XII inhibition, whereas halogeno, methoxy and dimethylamino moieties led to very potent CA XII inhibitors. PMID:23290254

  16. Factor IXMadrid 2: a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.

    PubMed

    Solera, J; Magallón, M; Martin-Villar, J; Coloma, A

    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' end of intron d and the two last coding nucleotides located at the 3' end of exon IV in the normal factor IX gene; this fragment has been replaced by a 47-bp sequence from the normal factor IX gene, although this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment.

  17. Factor IXMadrid 2: a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.

    PubMed Central

    Solera, J; Magallón, M; Martin-Villar, J; Coloma, A

    1992-01-01

    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' end of intron d and the two last coding nucleotides located at the 3' end of exon IV in the normal factor IX gene; this fragment has been replaced by a 47-bp sequence from the normal factor IX gene, although this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment. Images Figure 1 PMID:1346483

  18. Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism

    PubMed Central

    Chen, Dina; Seers, Christine A.; Mitchell, Helen A.; Chen, Yu-Yen; Glew, Michelle D.; Dashper, Stuart G.; Reynolds, Eric C.

    2015-01-01

    The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria. PMID:26340749

  19. PREFACE: IX International Conference on Modern Techniques of Plasma Diagnostics and their Application

    NASA Astrophysics Data System (ADS)

    Savjolov, A. S.; Dodulad, E. I.

    2016-01-01

    The IX Conference on ''Modern Techniques of Plasma Diagnosis and their Application'' was held on 5 - 7 November, 2014 at National Research Nuclear University MEPhI (NRNU MEPhI). The goal of the conference was an exchange of information on both high-temperature and low-temperature plasma diagnostics as well as deliberation and analysis of various diagnostic techniques and their applicability in science, industry, ecology, medicine and other fields. The Conference also provided young scientists from scientific centres and universities engaged in plasma diagnostics with an opportunity to attend the lectures given by the leading specialists in this field as well as present their own results and findings. The first workshop titled ''Modern problems of plasma diagnostics and their application for control of chemicals and the environment'' took place at Moscow Engineering and Physics Institute (MEPhI) in June 1998 with the support of the Section on Diagnostics of the Council of Russian Academic of Science on Plasma Physics and since then these forums have been held at MEPhI every two years. In 2008 the workshop was assigned a conference status. More than 150 specialists on plasma diagnostics and students took part in the last conference. They represented leading Russian scientific centres (such as Troitsk Institute of Innovative and Thermonuclear Research, National Research Centre ''Kurchatov Institute'', Russian Federal Nuclear Centre - All-Russian Scientific Research Institute of Experimental Physics and others) and universities from Belarus, Ukraine, Germany, USA, Belgium and Sweden. About 30 reports were made by young researchers, students and post-graduate students. All presentations during the conference were broadcasted online over the internet with viewers in Moscow, Prague, St. Petersburgh and other cities. The Conference was held within the framework of the Centre of Plasma, Laser Research and Technology supported by MEPhI Academic Excellence Project (Russian

  20. Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism.

    PubMed

    Gorasia, Dhana G; Veith, Paul D; Chen, Dina; Seers, Christine A; Mitchell, Helen A; Chen, Yu-Yen; Glew, Michelle D; Dashper, Stuart G; Reynolds, Eric C

    2015-09-01

    The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria.

  1. Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis

    PubMed Central

    van Kuijk, Simon J. A.; Yaromina, Ala; Houben, Ruud; Niemans, Raymon; Lambin, Philippe; Dubois, Ludwig J.

    2016-01-01

    Hypoxia is a characteristic of many solid tumors and an adverse prognostic factor for treatment outcome. Hypoxia increases the expression of carbonic anhydrase IX (CAIX), an enzyme that is predominantly found on tumor cells and is involved in maintaining the cellular pH balance. Many clinical studies investigated the prognostic value of CAIX expression, but most have been inconclusive, partly due to small numbers of patients included. The present meta-analysis was therefore performed utilizing the results of all clinical studies to determine the prognostic value of CAIX expression in solid tumors. Renal cell carcinoma was excluded from this meta-analysis due to an alternative mechanism of upregulation. 958 papers were identified from a literature search performed in PubMed and Embase. These papers were independently evaluated by two reviewers and 147 studies were included in the analysis. The meta-analysis revealed strong significant associations between CAIX expression and all endpoints: overall survival [hazard ratio (HR) = 1.76, 95% confidence interval (95%CI) 1.58–1.98], disease-free survival (HR = 1.87, 95%CI 1.62–2.16), locoregional control (HR = 1.54, 95%CI 1.22–1.93), disease-specific survival (HR = 1.78, 95%CI 1.41–2.25), metastasis-free survival (HR = 1.82, 95%CI 1.33–2.50), and progression-free survival (HR = 1.58, 95%CI 1.27–1.96). Subgroup analyses revealed similar associations in the majority of tumor sites and types. In conclusion, these results show that patients having tumors with high CAIX expression have higher risk of locoregional failure, disease progression, and higher risk to develop metastases, independent of tumor type or site. The results of this meta-analysis further support the development of a clinical test to determine patient prognosis based on CAIX expression and may have important implications for the development of new treatment strategies. PMID:27066453

  2. 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.

  3. A-Single Spermatogonia Heterogeneity and Cell Cycles Synchronize with Rat Seminiferous Epithelium Stages VIII–IX1

    PubMed Central

    Abid, Shadaan N.; Richardson, Timothy E.; Powell, Heather M.; Jaichander, Priscilla; Chaudhary, Jaideep; Chapman, Karen M.; Hamra, F. Kent

    2014-01-01

    ABSTRACT In mammalian testes, “A-single” spermatogonia function as stem cells that sustain sperm production for fertilizing eggs. Yet, it is not understood how cellular niches regulate the developmental fate of A-single spermatogonia. Here, immunolabeling studies in rat testes define a novel population of ERBB3+ germ cells as approximately 5% of total SNAP91+ A-single spermatogonia along a spermatogenic wave. As a function of time, ERBB3+ A-single spermatogonia are detected during a 1- to 2-day period each 12.9-day sperm cycle, representing 35%–40% of SNAP91+ A-single spermatogonia in stages VIII–IX of the seminiferous epithelium. Local concentrations of ERBB3+ A-single spermatogonia are maintained under the mean density measured for neighboring SNAP91+ A-single spermatogonia, potentially indicative of niche saturation. ERBB3+ spermatogonia also synchronize their cell cycles with epithelium stages VIII–IX, where they form physical associations with preleptotene spermatocytes transiting the blood-testis barrier and Sertoli cells undergoing sperm release. Thus, A-single spermatogonia heterogeneity within this short-lived and reoccurring microenvironment invokes novel theories on how cellular niches integrate with testicular physiology to orchestrate sperm development in mammals. PMID:24389876

  4. Breeding of transgenic cattle for human coagulation factor IX by a combination of lentiviral system and cloning.

    PubMed

    Monzani, P S; Sangalli, J R; De Bem, T H C; Bressan, F F; Fantinato-Neto, P; Pimentel, J R V; Birgel-Junior, E H; Fontes, A M; Covas, D T; Meirelles, F V

    2013-02-28

    Recombinant coagulation factor IX must be produced in mammalian cells because FIX synthesis involves translational modifications. Human cell culture-based expression of human coagulation factor IX (hFIX) is expensive, and large-scale production capacity is limited. Transgenic animals may greatly increase the yield of therapeutic proteins and reduce costs. In this study, we used a lentiviral system to obtain transgenic cells and somatic cell nuclear transfer (SCNT) to produce transgenic animals. Lentiviral vectors carrying hFIX driven by 3 bovine β-casein promoters were constructed. Bovine epithelial mammary cells were transduced by lentivirus, selected with blasticidin, plated on extracellular matrix, and induced by lactogenic hormones; promoter activity was evaluated by quantitative PCR. Transcriptional activity of the 5.335-kb promoter was 6-fold higher than the 3.392- and 4.279-kb promoters, which did not significantly differ. Transgenic bovine fibroblasts were transduced with lentivirus carrying the 5.335-kb promoter and used as donor cells for SCNT. Cloned transgenic embryo production yielded development rates of 28.4%, similar to previous reports on cloned non-transgenic embryos. The embryos were transferred to recipient cows (N = 21) and 2 births of cloned transgenic cattle were obtained. These results suggest combination of the lentiviral system and cloning may be a good strategy for production of transgenic cattle.

  5. Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

    NASA Astrophysics Data System (ADS)

    Jiang, Ching-Fen; Wang, Chih-Yu; Chiang, Chun-Ping

    2011-07-01

    Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R/B ratio, and R/G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R/G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

  6. Bbb CP2 and Bbb CP1 sigma models in supergravity: Bianchi type IX instantons and cosmologies

    NASA Astrophysics Data System (ADS)

    Akbar, M. M.; D'Eath, P. D.

    2004-05-01

    We find instanton/cosmological solutions with biaxial Bianchi-IX symmetry, involving nontrivial spatial dependence of the {\\bb C} P^{1} - and {\\bb C} P^{2} -sigma-models coupled to gravity. Such manifolds arise in N = 1, d = 4 supergravity with supermatter actions and hence the solutions can be embedded in supergravity. There is a natural way in which the standard coordinates of these manifolds can be mapped into the four-dimensional physical space. Due to its special symmetry, we start with {\\bb C} P^{2} with its corresponding scalar ansatz; this further requires the spacetime to be SU(2) × U(1)-invariant. The problem then reduces to a set of ordinary differential equations whose analytical properties and solutions are discussed. Among the solutions there is a surprising, special family of exact solutions which owe their existence to the nontrivial topology of {\\bb C} P^{2} and are in 1-1 correspondence with matter-free Bianchi-IX metrics. These solutions can also be found by coupling {\\bb C} P^{1} to gravity. The regularity of these Euclidean solutions is discussed—the only possibility is bolt-type regularity. The Lorentzian solutions with similar scalar ansatz are all obtainable from the Euclidean solutions by Wick rotation.

  7. Comparative in vivo study of precursors of PpIX (ALA and MAL) used topically in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rego, Raquel F.; Inada, Natalia M.; Ferreira, Juliana; Araújo-Moreira, Fernando M.; Bagnato, Vanderlei S.

    2009-06-01

    The efficacy of Photodynamic Therapy (PDT) combined with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) in treatment of cancer has been studied for over ten years. However, there is no established dose for the topical use of these drugs in PDT. The purpose of this study was the comparison of induced PDT response of ALAsense (5-aminolevulinic acid - ALA) and Metvix (methyl aminolevulinate - MAL). Depth of necrosis induced by PDT was analyzed in normal liver of male Wistar rats, using different light doses and topical application of both PpIX precursors - ALA and MAL. PDT was performed with a diode laser at 630 nm with different doses of light (20, 50, 100 and 200 J/cm2), and intensity of 250 mW/cm2. Depth of necrosis analysis was used to calculate the threshold dose for each drug. The results showed that MAL-PDT presented a better response than ALA-PDT, mainly due to formulation differences. Moreover, the ability of the ALA PpIX production was more efficient.

  8. [Structural-functional organization of the cells of Brc-1 mutant Chlamydomonas reinhardtii, supplying protoporphyrin IX in the dark].

    PubMed

    Ladygin, V G; Chekunova, E M; Semenova, G A; Kosobriukhov, A A

    2014-01-01

    The structural-functional characteristics of the cells of wild type CC-124 and Brc-1 mutant of the unicellular green algae Chlamydomonas reinhardtii while growing in the dark and light were studied. It has been shown that the cells of the wild type in heterotrophic and mixotrophic growth conditions had a well developed structure and high functional activity due to the ability of the cells to synthesize chlorophyll both in the light and in the dark. The cells of Brc-1 mutant lost their ability to synthesize chlorophyll in the dark and the cells' color was orange due to brc-1 mutation in the nuclear gene LTS3 that regulated the activity of Mg-chelatase enzyme. In the dark the mutant cells accumulated protoporphyrin IX and had a weakly developed structure with low functional activity. It has been ascertained that due to high content of protoporphyrin IX even a short-term exposure of the cells of Brc-1 mutant to the light was accompanied by very strong destructive changes in all the membranes in a cell: plasmalemma, chloroplast, mitochondrion, shells of the nucleus and vacuoles. The reasons of these significant damages of the membrane components and O2-gas exchange in the cells of Brc-1 mutant are discussed.

  9. VizieR Online Data Catalog: MYStIX: Mid-IR observations and catalogs (Kuhn+, 2013)

    NASA Astrophysics Data System (ADS)

    Kuhn, M. A.; Povich, M. S.; Luhman, K. L.; Getman, K. V.; Busk, H. A.; Feigelson, E. D.

    2014-01-01

    The GLIMPSE survey is a Legacy Science Program of NASA's Spitzer Space Telescope to study star formation in the disk of the Milky Way Galaxy. It contains six MYStIX regions - the Lagoon Nebula, the Trifid Nebula, NGC 6334, the Eagle Nebula, M 17, and NGC 6357 - within the 2° wide strip along the Galactic equator (GLIMPSE I and II data releases). Furthermore, Spitzer images and photometry for RCW 38 and NGC 3576 come from the Vela-Carina survey (Majewski et al. 2007sptz.prop40791M), using a similar observing strategy with mosaicking and photometric analysis performed with the GLIMPSE pipeline. We obtained publicly available raw IRAC images from the Spitzer Heritage Archive for nine MYStIX regions without GLIMPSE coverage. The target list and details of the Astronomical Observation Requests (AORs) are provided in Table 1. The camera spatial resolutions are FWHM=1.6" to 1.9" from 3.6 to 8.0um. (3 data files).

  10. Overview of the Massive Young Star-Forming Complex Study in Infrared and X-Ray (MYStIX) Project

    NASA Astrophysics Data System (ADS)

    Feigelson, Eric D.; Townsley, Leisa K.; Broos, Patrick S.; Busk, Heather A.; Getman, Konstantin V.; King, Robert R.; Kuhn, Michael A.; Naylor, Tim; Povich, Matthew S.; Baddeley, Adrian; Bate, Matthew R.; Indebetouw, Remy; Luhman, Kevin L.; McCaughrean, Mark J.; Pittard, Julian M.; Pudritz, Ralph E.; Sills, Alison; Song, Yong; Wadsley, James

    2013-12-01

    The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) seeks to characterize 20 OB-dominated young clusters and their environs at distances d <= 4 kpc using imaging detectors on the Chandra X-ray Observatory, Spitzer Space Telescope, and the United Kingdom InfraRed Telescope. The observational goals are to construct catalogs of star-forming complex stellar members with well-defined criteria and maps of nebular gas (particularly of hot X-ray-emitting plasma) and dust. A catalog of MYStIX Probable Complex Members with several hundred OB stars and 31,784 low-mass pre-main sequence stars is assembled. This sample and related data products will be used to seek new empirical constraints on theoretical models of cluster formation and dynamics, mass segregation, OB star formation, star formation triggering on the periphery of H II regions, and the survivability of protoplanetary disks in H II regions. This paper gives an introduction and overview of the project, covering the data analysis methodology and application to two star-forming regions: NGC 2264 and the Trifid Nebula.

  11. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    PubMed Central

    Monroe, Dougald M.; Jenny, Richard J.; Van Cott, Kevin E.; Saward, Laura L.

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  12. SHIP-2 forms a tetrameric complex with filamin, actin, and GPIb-IX-V: localization of SHIP-2 to the activated platelet actin cytoskeleton.

    PubMed

    Dyson, Jennifer M; Munday, Adam D; Kong, Anne M; Huysmans, Richard D; Matzaris, Maria; Layton, Meredith J; Nandurkar, Harshal H; Berndt, Michael C; Mitchell, Christina A

    2003-08-01

    The platelet receptor for the von Willebrand factor (VWF) glycoprotein Ib-IX-V (GPIb-IX-V) complex mediates platelet adhesion at sites of vascular injury. The cytoplasmic tail of the GPIbalpha subunit interacts with the actin-binding protein, filamin, anchoring the receptor in the cytoskeleton. In motile cells, the second messenger phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3) induces submembraneous actin remodeling. The inositol polyphosphate 5-phosphatase, Src homology 2 domain-containing inositol polyphosphate 5-phosphatase-2 (SHIP-2), hydrolyzes PtdIns(3,4,5)P3 forming phosphatidylinositol 3,4 bisphosphate (PtdIns(3,4)P2) and regulates membrane ruffling via complex formation with filamin. In this study we investigate the intracellular location and association of SHIP-2 with filamin, actin, and the GPIb-IX-V complex in platelets. Immunoprecipitation of SHIP-2 from the Triton-soluble fraction of unstimulated platelets demonstrated association between SHIP-2, filamin, actin, and GPIb-IX-V. SHIP-2 associated with filamin or GPIb-IX-V was active and demonstrated PtdIns(3,4,5)P3 5-phosphatase activity. Following thrombin or VWF-induced platelet activation, detection of the SHIP-2, filamin, and receptor complex decreased in the Triton-soluble fraction, although in control studies the level of SHIP-2, filamin, or GPIb-IX-V immunoprecipitated by their respective antibodies did not change following platelet activation. In activated platelets spreading on a VWF matrix, SHIP-2 localized intensely with actin at the central actin ring and colocalized with actin and filamin at filopodia and lamellipodia. In spread platelets, GPIb-IX-V localized to the center of the platelet and showed little colocalization with filamin at the plasma membrane. These studies demonstrate a functionally active complex between SHIP-2, filamin, actin, and GPIb-IX-V that may orchestrate the localized hydrolysis of PtdIns(3,4,5)P3 and thereby regulate cortical and submembraneous actin.

  13. Overexpression of Intrinsic Hypoxia Markers HIF1{alpha} and CA-IX Predict for Local Recurrence in Stage T1-T2 Glottic Laryngeal Carcinoma Treated With Radiotherapy

    SciTech Connect

    Schrijvers, M.L.; Laan, B.F.A.M. van der; Bock, G.H. de; Pattje, W.J.; Mastik, M.F.; Menkema, L.; Langendijk, J.A.; Kluin, P.M.; Schuuring, E.; Wal, J.E. van der

    2008-09-01

    Purpose: To examine the prognostic value of three endogenous hypoxia markers (hypoxia inducible factor 1 {alpha} subunit [HIF1{alpha}], carbonic anhydrase IX [CA-IX], and glucose transporter type 1 [GLUT-1]) on the clinical outcome in patients with early-stage glottic carcinoma primarily treated with radiotherapy (RT) and to determine the predictive hypoxic profile to choose the optimal treatment of early-stage laryngeal carcinoma. Methods and Materials: Immunohistochemistry for HIF1{alpha}, CA-IX, and GLUT-1 was performed on formalin-fixed, paraffin-embedded, pretreatment tissue samples of 91 glottic squamous cell carcinoma specimens. The patient group consisted only of those with early-stage (T1-T2) glottic carcinoma, and all patients were treated with RT only. Relative tumor staining was scored on the tissue samples. Receiver operating curve analysis was performed to determine the optimal cutoff value for each tumor marker. Cox regression analyses for the variables HIF1{alpha}, CA-IX, GLUT-1, gender, age, hemoglobin level, T category, N category, tobacco use, and alcohol use were performed with local control and overall survival as endpoints. Results: HIF1{alpha} overexpression in early-stage glottic carcinoma correlated significantly with worse local control (hazard ratio [HR], 3.05; p = 0.021) and overall survival (HR, 2.92; p = 0.016). CA-IX overexpression correlated significantly with worse local control (HR, 2.93; p = 0.020). GLUT-1 overexpression did not show any correlation with the clinical outcome parameters. Tumors with a nonhypoxic profile (defined as low HIF1{alpha} and low CA-IX expression) had significantly better local control (HR, 6.32; p 0.013). Conclusion: The results of our study have shown that early-stage glottic laryngeal carcinomas with low HIF1{alpha} and CA-IX expression are highly curable with RT. For this group, RT is a good treatment option. For tumors with HIF1{alpha} or CA-IX overexpression, hypoxic modification before RT or primary

  14. Analysis of potential functional regions using local degeneracy: mutational hotspots in human factor IX are localized in high-degeneracy regions.

    PubMed

    Xu, J; Chen, R; Xiao, Z X

    1994-11-15

    To study the relationship between the potential functional regions with the primary amino acid sequence, we introduced a new factor termed local degeneracy to analyze the degree of the degeneracy in a given segment of the protein. Using the defined local degeneracy, we have analyzed the human coagulation Factor IX (Christmas factor) which is an essential component of the clotting cascade. The mutational hotspots in Factor IX are primarily distributed in the high-degeneracy regions, suggesting a direct correlation of the functional regions with high degree of the degeneracy. This method may be useful to predict and to evaluate potential functional domains of a protein.

  15. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    PubMed

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  16. Civil Rights: Civil Rights Act of 1964 (Amended 1972, 1975, 1978), Title VI, Title VII [and] Educational Amendments of 1972, Title IX. Legal Modules for Vocational Cooperative Education.

    ERIC Educational Resources Information Center

    Western Michigan Univ., Kalamazoo.

    This module deals with various state and federal legislation pertaining to the civil rights of students enrolled in vocational cooperative programs in Michigan. Covered in the module are Title VI and Title VII of the Civil Rights Act of 1964 and Title IX of the Education Amendments of 1972 as well as Michigan civil rights legislation. The module,…

  17. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

    PubMed

    Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

    2014-11-01

    A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates. PMID:25267005

  18. How Title IX and Proportionality Population Concepts Have Equalized Collegiate Women's Sports Programs with Men's Sports and Allows Spillover Gains for Women in the Workplace

    ERIC Educational Resources Information Center

    Compton, Nina H.; Compton, J. Douglas

    2010-01-01

    Title IX of the Education Reformation Act was passed in 1972 for the purpose of providing equality between males and females in intercollegiate sports. Since its inception the disparity between men's and women's varsity athletics programs has persisted throughout American colleges and universities. Discrimination and equal protection concerns…

  19. Title VI and Title IX Compliance by the Office for Civil Rights in State-Operated Special Purpose and Vocational Schools Pursuant to Adams v. Mathews.

    ERIC Educational Resources Information Center

    McClure, Phyllis

    This paper examines the compliance activities of the Office for Civil Rights (OCR) undertaken to eliminate racial and sex discrimination in special purpose schools administered by State departments of education. After reviewing background to non-enforcement of Title VI, and briefly explaining Title IX, the activities of OCR with regard to special…

  20. Equal Educational Opportunity and Nondiscrimination for Girls in Advanced Mathematics, Science, and Technology Education: Federal Enforcement of Title IX. Equal Educational Opportunity Project Series, Volume V.

    ERIC Educational Resources Information Center

    Aneckstein, Laura; Baird, Andrea; Butler, Margaret; Chambers, David; Johnson, Wanda; Kraus, Rebecca; Mann, Eric; Trost, Tami; Zalokar, Nadja; Zieseniss, Mireille

    This report focuses on the Office for Civil Rights' (OCR's) activities relating to Title IX and advanced mathematics, science, and technology education for girls. It examines some of the barriers and inequities that undermine girls' opportunities to choose college majors and enter careers in the advanced mathematics, science, and technology…

  1. Data Summary Report for the Annual Fourmile Branch and F- and H-Area Seeplines, Appendix IX Metals and Radionuclides, 1998

    SciTech Connect

    Koch, J.

    1999-08-23

    This report presents a summary of the definitive data validation and verification for the 1998 RFI/RI annual Appendix IX metals and radionuclides survey for Fourmile Branch and the F- and H-Area Seeplines. The validation process began with project mobilization and continued through the delivery of EDDs and this report.

  2. ADVANCES AND CHALLENGES IN SUGARCANE BIOTECHNOLOY AND PLANT PATHOLOGY: A REVIEW OF THE IX PLANT PATHOLOGY WORKSHOP AND VI MOLECULAR BIOLOGY WORKSHOP

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The IX Pathology Workshop and VI Molecular Biology Workshop of the International Society of Sugar Cane Technologists (ISSCT) were organised jointly and hosted by the Colombian Sugarcane Research Centre (CENICAÑA) from 23-27 June 2008 at the Radisson Royal Hotel in Cali, Colombia. The Workshop was we...

  3. Title IX and Equal Opportunity in Vocational and Technical Education: A Promise Still Owed to the Nation's Young Women. A Report of the National Women's Law Center.

    ERIC Educational Resources Information Center

    National Women's Law Center, Washington, DC.

    The extent of sex segregation in vocational and technical education (VTE) in U.S. high schools nearly 30 years after passage of Title IX of the Education Amendments of 1972 was examined in a national study. The key findings were as follows: (1) sex segregation is pervasive in high school-level VTE nationwide; (2) sex segregation results in…

  4. Trauma-Informed Response in the Age of Title IX: Considerations for College Counselors Working with Survivors of Power-Based Personal Violence

    ERIC Educational Resources Information Center

    Conley, Abigail H.; Griffith, Catherine

    2016-01-01

    Intimate partner violence, sexual violence, and stalking are pervasive in the United States, and college women are disproportionately affected by this power-based personal violence (PBPV). Title IX mandates that colleges and universities offer support services to trauma survivors, and college counselors should be prepared to meet this need.…

  5. 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.

  6. Differentiation and classification of phytoplasmas in the pigeon pea witches'-broom group (16SrIX): an update based on multiple gene sequence analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pigeon pea witches’-broom phytoplasma group (16SrIX) consists of diverse phytoplasma strains that cause numerous diseases in leguminous trees and herbaceous crops, vegetables, a fruit, a nut tree, and a forest tree. At least 14 strains have been reported worldwide. Comparative phylogenetic analyses ...

  7. 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

  8. 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

  9. Kinetics and comparison of δ-aminolevulinic-acid-induced endogenous protoporphyrin-IX in single cell by steady state and multiphoton fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Ganesan, Singaravelu; Elangovan, Masilamani; Periasamy, Ammasi

    2001-04-01

    Photodynamic Therapy has emerged as a new modality in the treatment of various nonmalignant and malignant diseases. It involves the systemic administration of tumor specific photo-sensitizers with the subsequent application of visible light. This combination causes the generation of cytotoxic species, which damage sensitive targets, producing cell injury and tumor destruction. Although, photofrin is the only photosensitizer currently approved for PDT and tumor detection, its concomitant cutaneous photosensitization poses a significant problem. Hence, δ-aminoleuvulinic acid (δ-ALA) a precursor for the endogenous production of Protoporphyrin IX, through heme biosynthesis pathway, has gained significant importance in the Photodynamic Therapy. Though δ-ALA is present naturally in the cells, exogenous δ-ALA helps to synthesis more of PpIX in the tumor cells, as the fast growing tumor cells take up the administered δ-ALA more than the normal cells. Based on these facts, many invasive studies have been reported on the kinetics of δ-ALA at cellular level by chemical extraction of PpIX from the cells. In the present study we have studied the kinetics of δ-ALA induced PpIX fluorescence from Hela cells by perchloric/Methanol extraction method. However, the amount of PpIX synthesized in the cells at different point of incubation time by noninvasive methods has not been reported. Hence we have also used a noninvasive technique of measuring the kinetics δ-ALA induced PPIX fluorescence from Hela, an epithelial cell derived from human cervical cancer by both single photon (steady state) and multi photon excitation. From the studies it is observed that the δ-ALA induced PpIX is more at 2 hours incubation time for 2 mM of δ-ALA concentration. Further, it is observed that with steady state fluorescence imaging method, the excitation light itself cause the Photodynamic damage, due to the prolonged exposure of the cells than in multi photon excitation, leading to the rounding

  10. Identification of the chlE gene encoding oxygen-independent Mg-protoporphyrin IX monomethyl ester cyclase in cyanobacteria.

    PubMed

    Yamanashi, Kaori; Minamizaki, Kei; Fujita, Yuichi

    2015-08-01

    The fifth ring (E-ring) of chlorophyll (Chl) a is produced by Mg-protoporphyrin IX monomethyl ester (MPE) cyclase. There are two evolutionarily unrelated MPE cyclases: oxygen-independent (BchE) and oxygen-dependent (ChlA/AcsF) MPE cyclases. Although ChlA is the sole MPE cyclase in Synechocystis PCC 6803, it is yet unclear whether BchE exists in cyanobacteria. A BLAST search suggests that only few cyanobacteria possess bchE. Here, we report that two bchE candidate genes from Cyanothece strains PCC 7425 and PCC 7822 restore the photosynthetic growth and bacteriochlorophyll production in a bchE-lacking mutant of Rhodobacter capsulatus. We termed these cyanobacterial bchE orthologs "chlE."

  11. Generation of the Ares I-X Flight Test Vehicle Aerodynamic Data Book and Comparison To Flight

    NASA Technical Reports Server (NTRS)

    Bauer, Steven X.; Krist, Steven E.; Compton, William B.

    2011-01-01

    A 3.5-year effort to characterize the aerodynamic behavior of the Ares I-X Flight Test Vehicle (AIX FTV) is described in this paper. The AIX FTV was designed to be representative of the Ares I Crew Launch Vehicle (CLV). While there are several differences in the outer mold line from the current revision of the CLV, the overall length, mass distribution, and flight systems of the two vehicles are very similar. This paper briefly touches on each of the aerodynamic databases developed in the program, describing the methodology employed, experimental and computational contributions to the generation of the databases, and how well the databases and underlying computations compare to actual flight test results.

  12. Establishing Approaches to Modeling the Ares I-X and Ares I Roll Control System with Free-stream Interaction

    NASA Technical Reports Server (NTRS)

    Pao, S. Paul; Deere, Karen A.; Abdol-Hamid, Khales S.

    2011-01-01

    Approaches were established for modeling the roll control system and analyzing the jet interactions of the activated roll control system on Ares-type configurations using the USM3D Navier-Stokes solver. Components of the modeling approach for the roll control system include a choice of turbulence models, basis for computing a dynamic equivalence of the real gas rocket exhaust flow in terms of an ideal gas, and techniques to evaluate roll control system performance for wind tunnel and flight conditions. A simplified Ares I-X configuration was used during the development phase of the roll control system modeling approach. A limited set of Navier-Stokes solutions was obtained for the purposes of this investigation and highlights of the results are included in this paper. The USM3D solutions were compared to equivalent solutions at select flow conditions from a real gas Navier- Stokes solver (Loci-CHEM) and a structured overset grid Navier-Stokes solver (OVERFLOW).

  13. Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function

    PubMed Central

    Jamali, Somayeh; Klier, Michael; Ames, Samantha; Felipe Barros, L.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

    2015-01-01

    The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H+-shuttle His200, functions as a “proton-collecting/distributing antenna” to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H+, as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions. PMID:26337752

  14. Recent trends and advances in food chemistry and analysis: research highlights from the IX Italian Congress of Food Chemistry.

    PubMed

    Novellino, Ettore; Ritieni, Alberto; Rastrelli, Luca

    2013-02-27

    The IX Italian Congress of Food Chemistry (ChimAlSi_2012) contributed 12 lectures, 66 conferences, and 290 posters to the wealth of food knowledge; these were presented in four sessions: food safety, analytical techniques, bioactive compounds, and nutraceuticals. Emerging topics were discussed in two workshops dealing with food contaminants, and food and health. It has been an excellent forum for passionate exchange of recent results obtained in traditional and emerging fields of food chemistry. The symposium allowed coverage of the broad diversity of food-related topics, comprising food contaminants and food quality and the application of analytical approaches, such as sensorial, physical, chemical, spectroscopic, hyphenated mass spectrometric, biological and chemometric techniques, as well as nutrition and health aspects.

  15. Photodynamic therapy for difficult-to-treat basal cell carcinomas: Do poorly responding BCCs lack accumulation of protoporphyrin IX after ALA/MAL application?

    NASA Astrophysics Data System (ADS)

    Sandberg, Carin; Paoli, John; Halldin, Christina B.; Gillstedt, Martin; Larkö, Olle; Wennberg, Ann-Marie; Ericson, Marica B.

    2009-06-01

    Photodynamic therapy (PDT) using topical application of aminolevulinic acid (ALA) and methylaminolevulinate (MAL) has become a popular therapeutic method for the treatment of non-melanoma skin cancers such as basal cell carcinomas (BCCs); however, the treatment response varies. An important question is if BCCs which respond poorly to PDT lack accumulation of protoporhyrin IX (PpIX) after ALA/MAL application. In connection to PDT, fluorescence diagnostics (FD) can be performed to detect PpIX within human skin. We investigated fluorescence images from 22 patients with 35 BCCs. They were evaluated with respect to the fluorescence contrast based on image analysis, which was considered to be a tool to non-invasively measure the PpIX-concentration. As expected the fluorescence contrast between tumor and normal skin was elevated after MAL-application; although no correlation between low fluorescence contrast and lack of treatment response could be observed. In a former study, we have also investigated the transdermal penetration of ALA and MAL in 27 BCCs in vivo using a microdialysis technique. In 15 of 16 BCCs in which the microdialysis catheter was located superficially (i.e. at a depth of less than 1 mm), therapeutic drug concentrations were detected;.however, in the 11 lesions with a deeper catheter location (below 1 mm) drug concentrations above the detection limit of the system were only obtained in 6 lesions (p=0.026). No difference between the transdermal penetration of MAL and ALA could be seen. Conclusions: Lack of PpIX fluorescence cannot entirely explain why some BCCs don't respond to PDT, but inadecuate concentrations within the full thickness of the tumor may play a role as microdialysis has shown.

  16. Microneedles rollers as a potential device to increase ALA diffusion and PpIX production: evaluations by wide-field fluorescence imaging and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Gracielli Sousa, R. Phamilla; de Menezes, Priscila F. C.; Fujita, Alessandra K. L.; Requena, Michelle B.; Govone, Angelo Biassi; Escobar, André; de Nardi, Andrigo B.; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2014-03-01

    One of the limitations of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is the poor ability to penetrate biological barriers of skin and the recurrence rates in treatments. This study aimed to identify possible signs of increased diffusion of ALA-induced PpIX by fluorescence images and fluorescence spectroscopy. The research was done using in vivo porcine skin model. Before the cream application, microholes was performed with microneedles rollers in only one direction, afterward the ALA cream was applied at a 2.5cm2 area in triplicate and an occlusive dressing was placed. PpIX production was monitored using fluorescence spectroscopy collected at skin surface after 70, 100, 140, and 180 minutes of ALA incubation. About 100 fluorescence spectra of each treatment were collected, distributed by about five points for each site. Wide-field fluorescence imaging was made after 70, 90, and 170 minutes after treatment. The results obtained by imaging analysis indicated increase of the PpIX diffusion in the skin surface using the microneedles rollers (MNs) before ALA application. Circular regions of red fluorescence around the microholes were observed. In addition, the fluorescence spectra showed a greater intensity (2 times as many) in groups microneedles rollers associated. In conclusion, our data shown greater homogeneity and PpIX production in the groups pre-treated with microneedles indicating that the technique can be used to greater uniformity of PpIX production throughout the area to be treated reducing the chances of recurrent tumor as well as has potential for decreasing the time of therapy. (FUNDING SUPPORT:CAPES, CNPq and FAPESP)

  17. Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, S. K.; Hassanali, N. S.; Johnson, C.; Wilson, B. C.

    2007-02-01

    This study investigates whether low level light treatment (LLLT) can enhance the expression of Peripheral-type mitochondrial benzodiazepine receptors (PBRs) on the glioma-derived tumour cell line, CNS-1, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, (PpIX) and related metabolites including coproporphyrin III are known to traffic via the PBRs on the outer mitochondrial membrane on their passage into or out of the mitochondria. Astrocyte-derived cells within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum light or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5μ10 5) were exposed to a range of LLLT doses (0, 1 or 5 J/cm2) using a fixed intensity of 10 mW/cm2 and subsequently harvested for cell viability, immunofluorescence or western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broadspectrum light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. These data suggest that by selectively increasing PBR expression in tumour cells, LLLT may facilitate enhanced cell kill using ALA-PDT without damaging surrounding normal brain.

  18. Identification of Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a Regulator of N-Acetylglucosaminyltransferase GnT-IX (GnT-Vb)*

    PubMed Central

    Korekane, Hiroaki; Park, Jong Yi; Matsumoto, Akio; Nakajima, Kazuki; Takamatsu, Shinji; Ohtsubo, Kazuaki; Miyamoto, Yasuhide; Hanashima, Shinya; Kanekiyo, Kenji; Kitazume, Shinobu; Yamaguchi, Yoshiki; Matsuo, Ichiro; Taniguchi, Naoyuki

    2013-01-01

    Our previous studies on a β1,6-N-acetylglucosaminyltransferase, GnT-IX (GnT-Vb), a homolog of GnT-V, indicated that the enzyme has a broad GlcNAc transfer activity toward N-linked and O-mannosyl glycan core structures and that its brain-specific gene expression is regulated by epigenetic histone modifications. In this study, we demonstrate the existence of an endogenous inhibitory factor for GnT-IX that functions as a key regulator for GnT-IX enzymatic activity in Neuro2a (N2a) cells. We purified this factor from N2a cells and found that it is identical to ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), as evidenced by mass spectrometry and by the knockdown and overexpression of ENPP3 in cultured cells. Kinetic analyses revealed that the mechanism responsible for the inhibition of GnT-IX caused by ENPP3 is the ENPP3-mediated hydrolysis of the nucleotide sugar donor substrate, UDP-GlcNAc, with the resulting generation of UMP, a potent and competitive inhibitor of GnT-IX. Indeed, ENPP3 knockdown cells had significantly increased levels of intracellular nucleotide sugars and displayed changes in the total cellular glycosylation profile. In addition to chaperones or other known regulators of glycosyltransferases, the ENPP3-mediated hydrolysis of nucleotide sugars would have widespread and significant impacts on glycosyltransferase activities and would be responsible for altering the total cellular glycosylation profile and modulating cellular functions. PMID:23960081

  19. The X-ray spectral evolution of the ultraluminous X-ray source Holmberg IX X-1

    NASA Astrophysics Data System (ADS)

    Luangtip, Wasutep; Roberts, Timothy P.; Done, Chris

    2016-08-01

    We present a new analysis of X-ray spectra of the archetypal ultraluminous X-ray source (ULX) Holmberg IX X-1 obtained by the Swift, XMM-Newton and NuSTAR observatories. This ULX is a persistent source, with a typical luminosity of ˜1040 erg s-1, that varied by a factor of 4-5 over eight years. We find that its spectra tend to evolve from relatively flat or two-component spectra in the medium energy band (1-6 keV), at lower luminosities, to a spectrum that is distinctly curved and disc-like at the highest luminosities, with the peak energy in the curved spectrum tending to decrease with increased luminosity. We argue that the spectral evolution of the ULX can be explained by super-Eddington accretion models, where in this case we view the ULX down the evacuated funnel along its rotation axis, bounded by its massive radiatively driven wind. The spectral changes then originate in enhanced geometric beaming as the accretion rate increases and wind funnel narrows, causing the scattered flux from the central regions of the supercritical flow to brighten faster than the isotropic thermal emission from the wind, and so the curved hard spectral component to dominate at the highest luminosities. The wind also Compton down-scatters photons at the edge of the funnel, resulting in the peak energy of the spectrum decreasing. We also confirm that Holmberg IX X-1 displays spectral degeneracy with luminosity, and suggest that the observed differences are naturally explained by precession of the black hole rotation axis for the suggested wind geometry.

  20. Live attenuated influenza viruses produced in a suspension process with avian AGE1.CR.pIX cells

    PubMed Central

    2012-01-01

    Background Current influenza vaccines are trivalent or quadrivalent inactivated split or subunit vaccines administered intramuscularly, or live attenuated influenza vaccines (LAIV) adapted to replicate at temperatures below body temperature and administered intranasally. Both vaccines are considered safe and efficient, but due to differences in specific properties may complement each other to ensure reliable vaccine coverage. By now, licensed LAIV are produced in embryonated chicken eggs. In the near future influenza vaccines for human use will also be available from adherent MDCK or Vero cell cultures, but a scalable suspension process may facilitate production and supply with vaccines. Results We evaluated the production of cold-adapted human influenza virus strains in the duck suspension cell line AGE1.CR.pIX using a chemically-defined medium. One cold-adapted A (H1N1) and one cold-adapted B virus strain was tested, as well as the reference strain A/PR/8/34 (H1N1). It is shown that a medium exchange is not required for infection and that maximum virus titers are obtained for 1 × 10-6 trypsin units per cell. 1 L bioreactor cultivations showed that 4 × 106 cells/mL can be infected without a cell density effect achieving titers of 1 × 108 virions/mL after 24 h. Conclusions Overall, this study demonstrates that AGE1.CR.pIX cells support replication of LAIV strains in a chemically-defined medium using a simple process without medium exchanges. Moreover, the process is fast with peak titers obtained 24 h post infection and easily scalable to industrial volumes as neither microcarriers nor medium replacements are required. PMID:23110398