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Sample records for licence ix 354c

  1. [Driver's licence: responsibility, ethics and deontology].

    PubMed

    Lucas, P

    1999-09-01

    The new law enacted on march 23rd 1998 regarding driving-licence, which became effective on october 1st 1998, modifies the method for obtaining the different types of driving-licences. Its 6th annex enumerates a list of physical impairments and pathologies implying the denial, the limitation or the withdrawal of the driving-licence; it determines if a medical advice, and if the case which kind of medical advice, is required. This leads to new situations, for which no jurisprudence has been established to date, where not only the responsibility of the licence's applicant but also that of the examining physician could be suspected. The physicians are also confronted to ethical an deontological problems on which the medical authorities have not always given an opinion. This paper examines them in order to give some bases for reflexion and discussion.

  2. Title IX Resource Guide

    ERIC Educational Resources Information Center

    Office for Civil Rights, US Department of Education, 2015

    2015-01-01

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

  3. 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

  4. 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…

  5. Regulation and the social licence for medical research.

    PubMed

    Dixon-Woods, Mary; Ashcroft, Richard E

    2008-12-01

    Regulation and governance of medical research is frequently criticised by researchers. In this paper, we draw on Everett Hughes' concepts of professional licence and professional mandate, and on contemporary sociological theory on risk regulation, to explain the emergence of research governance and the kinds of criticism it receives. We offer explanations for researcher criticism of the rules and practices of research governance, suggesting that these are perceived as interference in their mandate. We argue that, in spite of their complaints, researchers benefit from the institutions of governance and regulation, in particular by the ways in which regulation secures the social licence for research. While it is difficult to answer questions such as: "Is medical research over-regulated?" and "Does the regulation of medical research successfully protect patients or promote ethical conduct?", a close analysis of the social functions of research governance and its relationship to risk, trust, and confidence permits us to pose these questions in a more illuminating way.

  6. Intercollegiate Athletics and Title IX

    ERIC Educational Resources Information Center

    Cox, Thomas A.

    1977-01-01

    The application of Title IX and the HEW regulation to intercollegiate sports is described, and the relationships among Title IX, the equal protection doctrine, and the proposed equal rights amendment to the Constitution are assessed. (LBH)

  7. Licenced to transplant: UK overkill on EU Organ Directive provides golden opportunity for research.

    PubMed

    Cronin, Antonia J; Douglas, James; Sacks, Steven

    2012-10-01

    Progress in transplantation outcomes depends on continuing research into both donor and recipient factors that may enhance graft and patient survival. A system of licencing for transplantation research, introduced by the Human Tissue Act 2004, which separates it from the transplantation process (then exempt from licencing), has damaged this vital activity by a combination of inflexible interpretation of the 2004 Act and fear of criminal liability on the part of researchers. Now, following the European Union (EU) Directive (2010) on standards of quality and safety of human organs intended for transplantation, new UK Regulations have been drafted, which are intended to implement it. These Regulations impose a compulsory licencing system, similar to that for research, on the whole transplantation process. This goes beyond what is required by the Directive and may even have an inhibitory effect similar to that already seen in research. Initial draft Regulations went further, imposing criminal sanctions for breaches. However, following a public consultation process, the Department of Health (DH) has recently stated that, as a result of the overwhelming view of respondents that the proposed licencing system was unnecessary, all sanctions under the final Regulations are now decriminalised, with the sole exception of operating without a licence. While this does not eliminate the negative effect of licencing, it does suggest an awareness of the DH that excessive regulation unnecessarily harms the transplantation process. An opportunity thus arises for the Human Tissue Authority (the regulatory body for both the new licences and research licences under the 2004 Act) to end the current illogical and harmful separation of transplantation and transplantation research by ensuring that all centres licenced for organ donation, retrieval and transplantation are also fully licenced for related research.

  8. 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

  9. 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…

  10. Licence restrictions as an under-used strategy in managing older driver safety.

    PubMed

    Langford, Jim; Koppel, Sjaanie

    2011-01-01

    While many older drivers remain unimpaired or otherwise effectively compensate for functional deficits, a minority are currently faced with two main options: either continue to drive with arguably an unacceptable crash risk; or cease driving, perhaps at the instigation of licensing authorities. Licence restrictions represent a possible third option for some older drivers, by better managing crash risk while still allowing acceptable levels of mobility. The present study has explored licence restrictions as applied to Victorian older drivers over a ten-year period. It has identified the types of restrictions and their extent of use in recent years, plus indications of potential safety benefits that may result from restricted licencing practices. Less than 10% of the older driver cohort had a licence restriction and in around 95% of instances, the restriction related to the need to wear corrective lenses; these numbers precluded a conclusive evaluation of safety benefits. However, two important findings emerged. First, the imposition of a licence restriction was usually associated with a reduction in absolute crash rates. Second, three restrictions were identified that most readily form the basis of a graduated driving reduction program.

  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…

  12. Reconsidering the Status of Title IX.

    ERIC Educational Resources Information Center

    Hammer, Ben

    2003-01-01

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

  13. Hair testing is superior to urine to disclose cocaine consumption in driver's licence regranting.

    PubMed

    Polla, M; Stramesi, C; Pichini, S; Palmi, I; Vignali, C; Dall'Olio, G

    2009-08-10

    In driver licence regranting, subjects with a history of cocaine use are requested to undergo laboratory testing to verify both current and past abstinence from the drug. Identification of cocaine use based only on urinalysis may miss some cases because of the short elimination half-life of the drug. Moreover, many abusers know how to time their cocaine consumption in such a way that they can "beat" the urinalysis, having a series of negative urine tests. We report on the use of hair testing to disclose sporadic cocaine consumption in seven subjects attending the Local Medical Commission to reobtain driver licence, with constant negative urinalysis. Even with one or two weekly negative urine screens along several months, all the subjects were positive using hair testing for cocaine and benzoylecgonine, above the internationally recommended limit of quantification: 0.5 ng/mg and 0.05 ng/mg for cocaine and benzoylecgonine, respectively (concentration range for cocaine: 0.51-2.23 ng/mg hair; concentration range for benzoylecgonine: 0.08-1.70 ng/mg hair). The obtained results support strongly the use of hair testing for cocaine in drug addicts and occasional abusers applying for regranting of driver licence in order to minimize social risk behaviours.

  14. [Title IX and Intercollegiate Athletics.

    ERIC Educational Resources Information Center

    Department of Health , Education, and Welfare, Washington., DC. Office of the Secretary.

    Title IX of the 1972 Education Amendments is the topic of these Department of Health, Education, and Welfare (DHEW) notices, which include both a proposed policy interpretation regarding intercollegiate athletic programs and a proposed amendment regarding federal regulation of school dress codes. The purpose of the first action is to ensure that…

  15. Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-protoporphyrin IX and Mesoporphyrin IX.

    PubMed

    Cruz-Oliveira, Christine; Almeida, Andreza F; Freire, João M; Caruso, Marjolly B; Morando, Maria A; Ferreira, Vivian N S; Assunção-Miranda, Iranaia; Gomes, Andre M O; Castanho, Miguel A R B; Da Poian, Andrea T

    2017-03-27

    Virus resistance to antiviral therapies is an increasing concern that makes urgent the development of broad spectrum antiviral drugs. Targeting viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins, due to their relative hydrophobicity and pro-oxidant character, are good candidates for antivirals' development. In the present work, we characterized the antiviral activity of protoprophyrin IX (PPIX), Zn-protoporphyrin IX (ZnPPIX) and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV), and evaluated the mechanisms involved in this activity. VSV treatment with PPIX, ZnPPIX and MPIX promoted a dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and α-tocopherol partially protected VSV inactivation by porphyrins, suggesting that singlet oxygen ((1)O2) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore, (1)O2 was detected by DMA oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX and MPIX as good models for broad antiviral drug design.

  16. When to Renew Software Licences at HPC Centres? A Mathematical Analysis

    NASA Astrophysics Data System (ADS)

    Baolai, Ge; MacIsaac, Allan B.

    2010-11-01

    In this paper we study a common problem faced by many high performance computing (HPC) centres: When and how to renew commercial software licences. Software vendors often sell perpetual licences along with forward update and support contracts at an additional, annual cost. Every year or so, software support personnel and the budget units of HPC centres are required to make the decision of whether or not to renew such support, and usually such decisions are made intuitively. The total cost for a continuing support contract can, however, be costly. One might therefore want a rational answer to the question of whether the option for a renewal should be exercised and when. In an attempt to study this problem within a market framework, we present the mathematical problem derived for the day to day operation of a hypothetical HPC centre that charges for the use of software packages. In the mathematical model, we assume that the uncertainty comes from the demand, number of users using the packages, as well as the price. Further we assume the availability of up to date software versions may also affect the demand. We develop a renewal strategy that aims to maximize the expected profit from the use the software under consideration. The derived problem involves a decision tree, which constitutes a numerical procedure that can be processed in parallel.

  17. 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

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  18. 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

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  19. 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 [ ]....

  20. 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

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  1. 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...

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

    Code of Federal Regulations, 2010 CFR

    2016-10-01

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

  3. 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...

  4. 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

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  5. 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...

  6. 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...

  7. 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

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  8. 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

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  9. 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...

  10. 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...

  11. 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...

  12. 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

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  13. 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...

  14. 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...

  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

    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...

  17. 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...

  18. 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...

  19. 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 [ ]....

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

    Code of Federal Regulations, 2010 CFR

    2004-10-01

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

  1. 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...

  2. 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...

  3. Exonuclease IX of Escherichia coli.

    PubMed Central

    Shafritz, K M; Sandigursky, M; Franklin, W A

    1998-01-01

    The bacteria Escherichia coli contains several exonucleases acting on both double- and single-stranded DNA and in both a 5'-->3' and 3'-->5' direction. These enzymes are involved in replicative, repair and recombination functions. We have identified a new exonuclease found in E.coli, termed exonuclease IX, that acts preferentially on single-stranded DNA as a 3'-->5' exonuclease and also functions as a 3'-phosphodiesterase on DNA containing 3'-incised apurinic/apyrimidinic (AP) sites to remove the product trans -4-hydroxy-2-pentenal 5-phosphate. The enzyme showed essentially no activity as a deoxyribophosphodiesterase acting on 5'-incised AP sites. The activity was isolated as a glutathione S-transferase fusion protein from a sequence of the E.coli genome that was 60% identical to a 260 bp region of the small fragment of the DNA polymerase I gene. The protein has a molecular weight of 28 kDa and is free of AP endonuclease and phosphatase activities. Exonuclease IX is expressed in E.coli , as demonstrated by reverse transcription-PCR, and it may function in the DNA base excision repair and other pathways. PMID:9592142

  4. 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…

  5. Title IX and Home Economics Instruction

    ERIC Educational Resources Information Center

    Thurston, Paul W.

    1977-01-01

    The following are discussed with reference to title IX of the Education Amendments of 1972, which prohibit sex discrimination in federally-supported educational programs: What is title IX? The letter of the law--can the school limit home economics to girls? Is a school in noncompliance if over 75 percent of the students in a home economics class…

  6. 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…

  7. Platelet Glycoprotein Ib-IX and Malignancy

    DTIC Science & Technology

    2010-09-01

    cancer to metastatic disease . During the next year we propose to examine the relevance of platelet receptors in models of spontaneous metastasis. A...the prognosis for recovery from breast cancer cannot be under emphasized. Indeed, the spread of metastatic disease represents a fundamental change in...IX have been identified, including von Willebrand factor (vWF) and thrombin, illustrating platelet GP Ib-IX as a major initiator of platelet thrombus

  8. 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.

  9. How do user experiences with different transport modes affect the risk of traffic accidents? From the viewpoint of licence possession status.

    PubMed

    Nakai, Hiroshi; Usui, Shinnosuke

    2017-02-01

    Road accidents between different modes of transport-such as between automobiles and pedestrians, automobiles and bicycles, or automobiles and motorcycles-are frequent. In such cases, it is important to consider the other side's perspective. This involves the ability to correctly judge, for every given situation, how other people on the road perceive their surroundings and what they intend to do next. In this paper, we conduct two types of studies assuming that this kind of ability to consider perspectives is higher when the person is licenced to drive the mode of transport used by the other party. For Study 1, we analysed accidents involving senior citizens between the ages of 65 and 74 years, who collided with automobiles as pedestrians or cyclists (1656 and 3192 cases respectively), in terms of the accident category and type of road at the accident spot. The results indicate that possession or non-possession of a licence was irrelevant for accidents involving cyclists, but for accidents with pedestrians, senior citizens who did not possess a licence are likely to be involved in a greater number of accidents in places that require interaction with automobiles, such as while crossing at crosswalks or at intersections. For Study 2, we reviewed 875 ordinary first-class licence practical test examinees, categorised them according to their licence possession status (motorcycle licence, moped licence, or no licence), and made a category-wise comparison of the test instructor's assessment of their ability to make a left turn. The results showed that those who had a motorcycle or moped licence tended to make a left turn more safely. Thus, the results indicate that experience with different modes of transport is likely to reduce the risk of accidents. These findings may be used to popularise educational interventions encouraging users of various transport modes to consider the perspective of others (i.e. via perspective-taking).

  10. 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…

  11. 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

    ... policy, ; 86.9 Distribution, 86.9(c) Notification of policy, ; 86.9(a) Publications, 86.9(b) Dress codes... 45 Public Welfare 1 2010-10-01 2010-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH...

  12. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Distribution, 106.9(c) Notification of policy, ; 106.9(a) Publications, 106.9(b) Dress codes 106.31(b) (4) E... 34 Education 1 2010-07-01 2010-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of...

  13. Testing the impact of local alcohol licencing policies on reported crime rates in England

    PubMed Central

    De Vocht, F; Heron, J; Campbell, R; Egan, M; Mooney, J D; Angus, C; Brennan, A; Hickman, M

    2017-01-01

    Background Excessive alcohol use contributes to public nuisance, antisocial behaviour, and domestic, interpersonal and sexual violence. We test whether licencing policies aimed at restricting its spatial and/or temporal availability, including cumulative impact zones, are associated with reductions in alcohol-related crime. Methods Reported crimes at English lower tier local authority (LTLA) level were used to calculate the rates of reported crimes including alcohol-attributable rates of sexual offences and violence against a person, and public order offences. Financial fraud was included as a control crime not directly associated with alcohol abuse. Each area was classified as to its cumulative licensing policy intensity for 2009–2015 and categorised as ‘passive’, low, medium or high. Crime rates adjusted for area deprivation, outlet density, alcohol-related hospital admissions and population size at baseline were analysed using hierarchical (log-rate) growth modelling. Results 284 of 326 LTLAs could be linked and had complete data. From 2009 to 2013 alcohol-related violent and sexual crimes and public order offences rates declined faster in areas with more ‘intense’ policies (about 1.2, 0.10 and 1.7 per 1000 people compared with 0.6, 0.01 and 1.0 per 1000 people in ‘passive’ areas, respectively). Post-2013, the recorded rates increased again. No trends were observed for financial fraud. Conclusions Local areas in England with more intense alcohol licensing policies had a stronger decline in rates of violent crimes, sexual crimes and public order offences in the period up to 2013 of the order of 4–6% greater compared with areas where these policies were not in place, but not thereafter. PMID:27514936

  14. 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

  15. 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... Succession for the San Francisco Regional Office and its Field Offices (Region IX). This Order of Succession supersedes all previous Orders of Succession for HUD Region IX. DATES: Effective Date: October 9, 2012....

  16. The Restoration of Title IX: Implications for Higher Education.

    ERIC Educational Resources Information Center

    Sandler, Bernice R.

    This booklet helps institutions understand the restoration of Title IX of the Education Amendments of 1972 and changes resulting from the Civil Rights Restoration Act. Title IX prohibits sex discrimination in federally assisted education programs. A 1984 ruling held that Title IX covers only programs or activities funded with federal money. In…

  17. 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…

  18. Open to All: Title IX at 30.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC. Office of the Secretary.

    This document is a report to the secretary of education on the findings of the Secretary's Commission on Opportunities in Athletics. The Commission was charged with examining Title IX. Starting in June 2002, the 15-member commission collected information, analyzed issues, and obtained broad public input directed at improving the application of…

  19. Title IX Enforcement Called 'Deeply Troubling'

    ERIC Educational Resources Information Center

    Lipka, Sara; Wolverton, Brad

    2007-01-01

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

  20. 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…

  1. 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.

  2. Title IX Indian Education Toolkit. A Step-by-Step Guide to the Title IX Indian Education Formula Grant.

    ERIC Educational Resources Information Center

    Beller, Floyd

    Title IX is a federal Indian Education Formula Grant Program approved in 1972 and reauthorized five times, most recently in 1994. Title IX formula grants assist groups in providing sound educational programs and opportunities for American Indian and Alaska Native students. A 1997-98 survey of Title IX grantees revealed their need for help in…

  3. 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.

  4. 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.

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

    PubMed Central

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

    1978-01-01

    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

  6. Promoting Active Transport in Older Adolescents Before They Obtain Their Driving Licence: A Matched Control Intervention Study

    PubMed Central

    Simons, Dorien; Van Cauwenberg, Jelle; Van Dyck, Delfien; Vandelanotte, Corneel; de Geus, Bas; De Bourdeaudhuij, Ilse; Clarys, Peter; Deforche, Benedicte

    2016-01-01

    Background Active transport has great potential to increase physical activity in older adolescents (17–18 years). Therefore, a theory- and evidence-based intervention was developed aiming to promote active transport among older adolescents. The intervention aimed to influence psychosocial factors of active transport since this is the first step in order to achieve a change in behaviour. The present study aimed to examine the effect of the intervention on the following psychosocial factors: intention to use active transport after obtaining a driving licence, perceived benefits, perceived barriers, subjective norm, self-efficacy, habit and awareness towards active transport. Methods A matched control three-arm study was conducted and consisted of a pre-test post-test design with intervention and control schools in Flanders (northern part of Belgium). A lesson promoting active transport was implemented as the last lesson in the course ‘Driving Licence at School’ in intervention schools (intervention group 1). Individuals in intervention group 2 received this active transport lesson and, in addition, they were asked to become a member of a Facebook group on active transport. Individuals in the control group only attended the regular course ‘Driving Licence at School’. Participants completed a questionnaire assessing socio-demographics and psychosocial variables at baseline, post (after one week) and follow-up (after eight weeks). To assess intervention effects, multilevel linear mixed models analyses were performed. Results A sample of 441 older adolescents (56.8% female; 17.4 (0.7) years) was analysed. For awareness regarding the existence of car sharing schemes, a significant increase in awareness from baseline to post measurement was found within intervention group 1 (p = 0.001) and intervention group 2 (p = 0.030) compared to the control group in which no change was found. In addition, a significant increase in awareness from baseline to follow

  7. Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer.

    PubMed

    Li, Yuji; Dong, Ming; Sheng, Weiwei; Huang, Longping

    2016-04-01

    The aim of this study was to study the effects of carbonic anhydrase IX (CA IX) towards the invasion and metastasis of pancreatic cancer. The expressions of CA IX in 58 cases of pancreatic cancer and paired paracancerous normal tissues, obtained from 2005 to 2012 in the first Affiliated Hospital of China Medical University, were detected, as well as its expressions in different pancreatic cancer cell lines, aiming to detect the impacts of CA IX silencing towards the invasion and metastasis of pancreatic cancer cells. The CA IX expressions in 58 pancreatic cancer cases were higher than those in the paired paracancerous normal tissues (P < 0.01), and positively correlated with the tumor size and the UICC staging UICC (P < 0.05), the multivariate analysis showed that the high expression of CA IX was the independent risk factor towards the prognosis of pancreatic cancer (P < 0.05). The CA IX was highly expressed in AxPC-1 and Miapaca-2, and the interference effects were significant. CA IX silencing could significantly inhibit the invasion and metastasis of AxPC-1 and Miapaca. We support a pro-tumor role of CA IX in the development and progression of pancreatic cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  9. 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. PMID:27800264

  10. How do medical doctors in the European Union demonstrate that they continue to meet criteria for registration and licencing?

    PubMed

    Solé, Meritxell; Panteli, Dimitra; Risso-Gill, Isabelle; Döring, Nora; Busse, Reinhard; McKee, Martin; Legido-Quigley, Helena

    2014-12-01

    This paper reviews procedures for ensuring that physicians in the European Union (EU) continue to meet criteria for registration and the implications of these procedures for cross-border movement of health professionals following implementation of the 2005/36/EC Directive on professional qualifications. A questionnaire was completed by key informants in 10 EU member states, supplemented by a review of peer-reviewed and grey literature and a review conducted by key experts in each country. The questionnaire covered three aspects: actors involved in processes for ensuring continued adherence to standards for registration and/or licencing (such as revalidation), including their roles and functions; the processes involved, including continuing professional development (CPD) and/or continuing medical education (CME); and contextual factors, particularly those impacting professional mobility. All countries included in the study view CPD/CME as one mechanism to demonstrate that doctors continue to meet key standards. Although regulatory bodies in a few countries have established explicit systems of ensuring continued competence, at least for some doctors (in Belgium, Germany, Hungary, the Netherlands, Slovenia and the UK), self-regulation is considered sufficient to ensure that physicians are up to date and fit to practice in others (Austria, Finland, Estonia and Spain). Formal systems vary greatly in their rationale, structure, and coverage. Whereas in Germany, Hungary and Slovenia, systems are exclusively focused on CPD/CME, the Netherlands also includes peer review and minimum activity thresholds. Belgium and the UK have developed more complex mechanisms, comprising a review of complaints or compliments on performance and (in the UK) colleague and patient questionnaires. Systems for ensuring that doctors continue to meet criteria for registration and licencing across the EU are complex and inconsistent. Participation in CPD/CME is only one aspect of maintaining

  11. 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

  12. Enhancing protoporphyrin IX-induced PDT

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Pye, Andrew; Campbell, Sandra

    2009-06-01

    Photodynamic therapy (PDT) using porphyrin precursors is commonly used in dermatology. Evidence indicates that good clinical outcomes (associated with excellent cosmesis) can be achieved in superficial precancers and basal cell carcinoma (BCC), however, efficacy appears less favorable for thicker nodular BCC (nBCC) unless multiple PDT treatment cycles are performed. Enhancement is therefore required if nBCC lesions are to be treated effectively with a single PDT treatment. The most common technique currently being routinely employed clinically is the use of aminolevulinic acid (ALA) esters (usually methyl (MAL) or hexyl (HAL)). Standard dermatological PDT employing these porphyrin precursors already manipulates the normal heme biosynthesis pathway resulting in a temporary accumulation of the natural photosensitizer, protoporphyrin IX (PpIX). Further manipulation using iron chelating agents is possible however. In normal and malignant human cells in vitro, the novel iron chelating agent CP94 produced greater PPIX fluorescence when administered with ALA or MAL than either congener produced alone. CP94 was also significantly more effective than the clinically established iron chelating agent desferrioxamine (DFO). Topical application of ALA+CP94 to clinical nBCC lesions was a simple and safe treatment modification which produced a significant increase in clinical clearance when CP94 was included in the cream.

  13. Ares I-X Ascent Base Environments

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  14. Electron Impact Exciation of Fe IX

    NASA Astrophysics Data System (ADS)

    Tayal, Swaraj; Zatsarinny, Oleg

    2015-05-01

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

  15. 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.

  16. 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.

  17. 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…

  18. Beyond Title IX: Gender Equity Issues in Schools.

    ERIC Educational Resources Information Center

    NETWORK, Inc., Andover, MA.

    This document is one of a two-part set of publications. Both deal with equal education and provide a concise overview of Title IX and gender equity issues in education and steps to take to ensure nondiscrimination and equal education opportunity for all. Title IX of the Education Amendments of 1972 mandates that schools not deny any student…

  19. 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…

  20. 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…

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

    ERIC Educational Resources Information Center

    American Association of University Professors, 2016

    2016-01-01

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

  2. 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…

  3. 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).

  4. 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

  5. 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.

  6. Nitric oxide inhibits the formation of zinc protoporphyrin IX and protoporphyrin IX.

    PubMed

    Wakamatsu, Jun-ichi; Hayashi, Nobutaka; Nishimura, Takanori; Hattori, Akihito

    2010-01-01

    The aim of this study was to elucidate the mechanism by which curing agents, especially nitrite, inhibit the formation of zinc protoporphyrin IX (ZPP) in dry-cured hams such as Parma ham. The oxidation-reduction potential of model solutions was increased by the addition of nitrite, but it was not clear whether the formation of ZPP is inhibited by the oxidizing property of nitrite. The effect of nitric oxide (NO) produced from nitrite on the formation of ZPP was examined. The amount of ZPP formed was decreased by the addition of NO donors. The amount of protoporphyrin IX (PPIX), which is the precursor of ZPP, was also decreased by the addition of NO donors. It is concluded that NO produced from nitrite inhibited the formation of PPIX and ZPP was therefore not formed in cured meat products with the addition of nitrite or nitrate.

  7. Zn protoporphyrin IX is formed not from heme but from protoporphyrin IX.

    PubMed

    Wakamatsu, Jun-Ichi; Okui, Jun; Hayashi, Nobutaka; Nishimura, Takanori; Hattori, Akihito

    2007-12-01

    We examined the effects of exogenous myoglobin, a bivalent chelator, and nitrite on Zn protoporphyrin IX (ZPP) formation by using model systems. ZPP was formed in a model solution without addition of exogenous myoglobin. After incubation, the amount of ZPP in a model solution was increased but that of heme was not decreased compared with the amounts before incubation. Protoporphyrin IX (PPIX) instead of ZPP also accumulated in a model solution with addition of EDTA, but the amount of heme was not reduced. These results suggested that ZPP was not formed by the Fe-Zn substitution in heme but was formed by the insertion of Zn into PPIX, which was formed independently. The fact that the effects of various factors in model systems with/without addition of a bivalent chelator were similar suggested that ZPP formation was strongly affected by PPIX formation. Inhibition of PPIX formation by nitrite might be the reason for the low levels of ZPP in cured meats.

  8. Quantitative determination of Zn protoporphyrin IX, heme and protoporphyrin IX in Parma ham by HPLC.

    PubMed

    Wakamatsu, Jun-Ichi; Odagiri, Hiroko; Nishimura, Takanori; Hattori, Akihito

    2009-05-01

    We measured the contents of Zn protoporphyrin IX (ZPP), heme and protoporphyrin IX (PPIX) in Parma ham by simultaneous analysis using high-performance liquid chromatography (HPLC). Extraction with ethyl acetate-acetic acid (4:1) was suitable for the quantitative analysis of ZPP. The contents of heme, ZPP and PPIX in Parma ham were 15.0-29.9, 27.7-47.0 and 0.4-1.1μg/g, respectively, and total content of porphyrin was 43.7-76.6μg/g. The amount of ZPP in Parma ham was larger than that of heme, and ZPP accounted for 60-70% of all porphyrins.

  9. 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.

  10. 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.

  11. Comparison of expression systems for human fucosyltransferase IX.

    PubMed

    Stacke, Christina; Ziegelmüller, Patrick; Hahn, Ulrich

    2010-01-01

    Human fucosyltransferase IX (hFucT-IX) is a highly conserved alpha1,3 fucosyltransferase with a distinct acceptor and site specificity. hFucT-IX catalyses the transfer of activated fucose to a sugar acceptor, thereby forming the Lewis x epitope. This epitope is responsible for recognition phenomena throughout the body e.g. in tumour growth. Detailed characterisation of hFucT-IX structure-function relationships by kinetic and X-ray structure analysis is prerequisite to the development of enzyme inhibitors for clinical applications such as the suppression of tumour metastasis. For these analyses substantial amounts of hFucT-IX are desirable. Since hFucT-IX is not present in considerable amounts in common cells an overproduction of recombinant hFucT-IX is appropriate. To evaluate the best system for this overproduction we compared different strategies employing prokaryotes (Escherichia coli), mammalian cells and insect cells. Insect cells were tested using stable and baculoviral expression strategies. Current results favour the use of the baculoviral expression system for further experiments.

  12. 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.

  13. 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

  14. 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.

  15. Title IX and Intercollegiate Athletics in the Federal Appellate Courts: Myth vs. Reality.

    ERIC Educational Resources Information Center

    Pieronek, Catherine

    2000-01-01

    Focuses on the enforcement of the nondiscrimination provisions of Title IX in higher education, and shows how the courts have wrestled with the application of Title IX to college athletic programs over the past decade. Provides a history of Title IX enforcement and describes current approaches to evaluating Title IX compliance. (SLD)

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

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

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

  17. 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

  18. Photosensitizing effect of protoporphyrin IX in pigmented melanoma of mice.

    PubMed

    Juzenas, Petras; Juzeniene, Asta; Stakland, Silje; Iani, Vladimir; Moan, Johan

    2002-09-27

    No fluorescence of protoporphyrin IX (PpIX) was measured using a fiber optic probe in pigmented B16F10 melanoma in mice after topical application of 5-aminolevulinic acid methylester (ALA-Me). However, chemical extraction of tissues excised from mice after intratumoral administration of ALA-Me or its parent compound ALA revealed that this tumor had the capability to produce PpIX. Small amounts of endogenous porphyrins, mainly PpIX, were found in the melanoma not treated with these drugs. Topical application of ALA-Me followed by exposure with laser light (633nm) delayed the growth of the tumors slightly. Light alone also had a significant effect on the tumor growth.

  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. The effects of CA IX catalysis products within tumor microenvironment.

    PubMed

    Santi, Alice; Caselli, Anna; Paoli, Paolo; Corti, Denise; Camici, Guido; Pieraccini, Giuseppe; Taddei, Maria Letizia; Serni, Sergio; Chiarugi, Paola; Cirri, Paolo

    2013-10-29

    Solid tumors are composed of both cancer cells and various types of accessory cells, mainly fibroblasts, that collectively compose the so called tumor-microenvironment. Cancer-associated fibroblasts have been described to actively participate in cancer progression by establishing a cytokine-mediated as well as metabolic crosstalk with cancer cells. In the present paper we show that activated human fibroblasts are able to boost tumor cells proliferation and that this effect is greatly dependent on stromal carbonic anhydrase IX (CA IX) activity. In fact fibroblasts show a strong upregulation of CA IX expression upon activation by cancer cells, while CA IX products, protons and bicarbonate, exert differential effects on cancer cells proliferation. While acidification of extracellular pH, a typical condition of rapidly growing solid tumors, is detrimental for tumor cells proliferation, bicarbonate, through its organication, supplies cancer cells with intermediates useful to sustain their high proliferation rate. Here we propose a new kind of fibroblasts/tumor cells crosstalk within tumor microenvironment, mediated by stromal CA IX products, aimed to favor cancer cells growth, opening new perspectives on CA IX role in tumor microenvironment.

  1. 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.

  2. 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

  3. Muscle as a target for supplementary factor IX gene transfer.

    PubMed

    Hoffman, Brad E; Dobrzynski, Eric; Wang, Lixin; Hirao, Lauren; Mingozzi, Federico; Cao, Ou; Herzog, Roland W

    2007-07-01

    Immune responses to the factor IX (F.IX) transgene product are a concern in gene therapy for the X-linked bleeding disorder hemophilia B. The risk for such responses is determined by several factors, including the vector, target tissue, and others. Previously, we have demonstrated that hepatic gene transfer with adeno-associated viral (AAV) vectors can induce F.IX-specific immune tolerance. Muscle-derived F.IX expression, however, is limited by a local immune response. Here, skeletal muscle was investigated as a target for supplemental gene transfer. Given the low invasiveness of intramuscular injections, this route would be ideal for secondary gene transfer, thereby boosting levels of transgene expression. However, this is feasible only if immune tolerance established by compartmentalization of expression to the liver extends to other sites. Immune tolerance to human F.IX established by prior hepatic AAV-2 gene transfer was maintained after subsequent injection of AAV-1 or adenoviral vector into skeletal muscle, and tolerized mice failed to form antibodies or an interferon (IFN)-gamma(+) T cell response to human F.IX. A sustained increase in systemic transgene expression was obtained for AAV-1, whereas an increase after adenoviral gene transfer was transient. A CD8(+) T cell response specifically against adenovirus-transduced fibers was observed, suggesting that cytotoxic T cell responses against viral antigens were sufficient to eliminate expression in muscle. In summary, the data demonstrate that supplemental F.IX gene transfer to skeletal muscle does not break tolerance achieved by liver-derived expression. The approach is efficacious, if the vector for muscle gene transfer does not express immunogenic viral proteins.

  4. 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

  5. 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.

  6. 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.

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

    NASA Technical Reports Server (NTRS)

    Davis, Stephen R.; Askins, Bruce R.

    2010-01-01

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

  8. 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.

  9. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board.... Small Business Administration (SBA) Region IX Regulatory Fairness Board and the SBA Office of...

  10. 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... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972. The obligations imposed by this part are independent of obligations imposed by or pursuant to title IX of...

  11. 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... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972. The obligations imposed by this part are independent of obligations imposed by or pursuant to title IX of...

  12. 45 CFR 83.5 - Effect of title IX of the Education Amendments of 1972.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Effect of title IX of the Education Amendments of... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972. The obligations imposed by this part are independent of obligations imposed by or pursuant to title IX of...

  13. 45 CFR 83.5 - Effect of title IX of the Education Amendments of 1972.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Effect of title IX of the Education Amendments of... Purposes; Definitions; Coverage § 83.5 Effect of title IX of the Education Amendments of 1972. The obligations imposed by this part are independent of obligations imposed by or pursuant to title IX of...

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

    ERIC Educational Resources Information Center

    Bird, Patrick J.

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

  15. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 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, 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...

  18. 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...

  19. Significantly increased detection rate of drugs of abuse in urine following the introduction of new German driving licence re-granting guidelines.

    PubMed

    Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Dufaux, Bertin

    2012-02-10

    In this paper we present the first assessment of the new German driving licence re-granting medical and psychological assessment (MPA) guidelines by comparing over 3500 urine samples tested under the old MPA cut-offs to over 5000 samples tested under the new MPA cut-offs. Since the enzyme multiplied immunoassay technique (EMIT) technology used previously was not sensitive enough to screen for drugs at such low concentrations, as suggested by the new MPA guidelines, enzyme-linked immunosorbent assay (ELISA) screening kits were used to screen for the drugs of abuse at the new MPA cut-offs. The above comparison revealed significantly increased detection rates of drug use or exposure during the rehabilitation period as follows: 1.61, 2.33, 3.33, and 7 times higher for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, benzoylecgonine and amphetamine respectively. The present MPA guidelines seem to be more effective to detect non-abstinence from drugs of abuse and hence to detecting drivers who do not yet fulfil the MPA requirements to regain their revoked driving licence.

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

    ERIC Educational Resources Information Center

    Dahl, Gabriel Grawe

    2012-01-01

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

  1. 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.

  2. Twenty Years after Title IX: Women in Sports Media.

    ERIC Educational Resources Information Center

    Rubarth, Lisa

    1992-01-01

    Though things are better for women in sports media today, Title IX has barely affected their ability to successfully enter into men's sports reporting. The biggest issue is equal access to locker rooms. Women in sports media face less respect, double standards, lack of support, and salary discrepancy. (SM)

  3. 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…

  4. Implementing Title IX: Concerns of Undergraduate Physical Education Majors.

    ERIC Educational Resources Information Center

    Bain, Linda L.

    A survey of an equal number of male and female students in the University of Houston's secondary school physical education course articulates prospective teacher concerns regarding the implementation of the nondiscriminatory principles set forth in the Title IX ruling. In general, male students evidence greater overall concern about the ruling's…

  5. 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.

  6. 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.

  7. Methods of producing protoporphyrin IX and bacterial mutants therefor

    SciTech Connect

    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.

  8. Gender Equity in Intercollegiate Athletics: Determinants of Title IX Compliance

    ERIC Educational Resources Information Center

    Anderson, Deborah J.; Cheslock, John Jesse; Ehrenberg, Ronald G.

    2006-01-01

    Using new data on intercollegiate athletes, this article shows that recent improvement in Title IX compliance among NCAA Division I institutions was previously overestimated, and provides the first estimates of compliance in Divisions II and III. In addition, regression analyses investigate how institutional characteristics relate to the extent of…

  9. 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.

  10. Major role of local immune responses in antibody formation to factor IX in AAV gene transfer.

    PubMed

    Wang, L; Cao, O; Swalm, B; Dobrzynski, E; Mingozzi, F; Herzog, R W

    2005-10-01

    The risk of an immune response to the coagulation factor IX (F.IX) transgene product is a concern in gene therapy for the X-linked bleeding disorder hemophilia B. In order to investigate the mechanism of F.IX-specific lymphocyte activation in the context of adeno-associated viral (AAV) gene transfer to skeletal muscle, we injected AAV-2 vector expressing human F.IX (hF.IX) into outbred immune-competent mice. Systemic hF.IX levels were transiently detected in the circulation, but diminished concomitant with activation of CD4+ T and B cells. ELISPOT assays documented robust responses to hF.IX in the draining lymph nodes of injected muscle by day 14. Formation of inhibitory antibodies to hF.IX was observed over a wide range of vector doses, with increased doses causing stronger immune responses. A prolonged inflammatory reaction in muscle started at 1.5-2 months, but ultimately failed to eliminate transgene expression. By 1.5 months, hF.IX antigen re-emerged in circulation in approximately 70% of animals injected with high vector dose. Hepatic gene transfer elicited only infrequent and weaker immune responses, with higher vector doses causing a reduction in T-cell responses to hF.IX. In summary, the data document substantial influence of target tissue, local antigen presentation, and antigen levels on lymphocyte responses to F.IX.

  11. 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

  12. 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...

  13. 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...

  14. 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

  15. 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.

  16. Validation of LUCIO-Direct-ELISA kits for the detection of drugs of abuse in urine: application to the new German driving licence re-granting guidelines.

    PubMed

    Agius, Ronald; Nadulski, Thomas; Moore, Christine

    2012-02-10

    LUCIO-Direct-enzyme linked immunosorbent assay (ELISA) tests were validated for the screening of drugs of abuse cannabis, opiates, amphetamines and cocaine in urine for the new German medical and psychological assessment (MPA) guidelines with subsequent gas chromatographic-mass spectrometric (GC-MS) confirmation. The screening cut-offs corresponding to 10 ng/mL 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 50 ng/mL amphetamine, 25 ng/mL morphine and codeine and 30 ng/mL benzoylecgonine were chosen at the point where the number of false negatives was lower than 1%. Due to their accuracy, ease of use and rapid analysis, these ELISA tests are very promising for cases where a large proportion of the tests are expected to be negative such as for abstinence monitoring as part of the driving licence re-granting process.

  17. Aggressive therapy improves cirrhosis in glycogen storage disease type IX.

    PubMed

    Tsilianidis, Laurie A; Fiske, Laurie M; Siegel, Sara; Lumpkin, Chris; Hoyt, Kate; Wasserstein, Melissa; Weinstein, David A

    2013-06-01

    Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.

  18. Bianchi-IX, Darboux-Halphen and Chazy-Ramanujan

    NASA Astrophysics Data System (ADS)

    Chanda, Sumanto; Guha, Partha; Roychowdhury, Raju

    2016-02-01

    Bianchi-IX four metrics are SU(2) invariant solutions of vacuum Einstein equation, for which the connection-wise self-dual case describes the Euler top, while the curvature-wise self-dual case yields the Ricci flat classical Darboux-Halphen system. It is possible to see such a solution exhibiting Ricci flow. The classical Darboux-Halphen system is a special case of the generalized one that arises from a reduction of the self-dual Yang-Mills equation and the solutions to the related homogeneous quadratic differential equations provide the desired metric. A few integrable and near-integrable dynamical systems related to the Darboux-Halphen system and occurring in the study of Bianchi-IX gravitational instanton have been listed as well. We explore in details whether self-duality implies integrability.

  19. 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.

  20. 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.

  1. 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

  2. Loop quantum cosmology of Bianchi type IX models

    NASA Astrophysics Data System (ADS)

    Wilson-Ewing, Edward

    2010-08-01

    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.

  3. 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.

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

    NASA Technical Reports Server (NTRS)

    Davis, Stephan R.; Askins, Bruce

    2009-01-01

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

  5. 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.

  6. Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors.

    PubMed

    Ditte, Peter; Dequiedt, Franck; Svastova, Eliska; Hulikova, Alzbeta; Ohradanova-Repic, Anna; Zatovicova, Miriam; Csaderova, Lucia; Kopacek, Juraj; Supuran, Claudiu T; Pastorekova, Silvia; Pastorek, Jaromir

    2011-12-15

    In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment.

  7. Optimization and characterization of the endogenous production of protoporphyrin IX in a yeast model

    NASA Astrophysics Data System (ADS)

    Joniová, Jaroslava; Gerelli, Emmanuel; Zellweger, Matthieu; Wagnières, Georges

    2016-12-01

    The availability of reproducible, convenient, and inexpensive model organisms able to generate predictable levels of endogenous porphyrins, including protoporphyrin IX (PpIX), is essential in photomedicine research. Saccharomyces cerevisiae produces endogenous PpIX and was used as a model organism for this study with the aim to maximize endogenous PpIX fluorescence intensity. It was found that PpIX fluorescence was significantly enhanced by administration of 5-aminolevulinic acid (ALA) and 2,2‧-bipyridyl. Fluorescence intensity and spectroscopy of PpIX produced endogenously were measured in diluted yeast solutions under various conditions. The optimal protocol was: 5 μM ALA and 1 mM 2,2‧-bipyridyl administered synchronously at 32°C. After 3 h, PpIX in yeast demonstrated similar steady-state and time-resolved spectroscopy as that of PpIX in DMSO. Moreover, under hypoxic conditions, the reciprocal lifetime of PpIX delayed fluorescence measured in real time was correlated to the partial pressure of oxygen (pO2) measured concomitantly with a commercially available pO2 probe. These data show that yeast can, in optimal conditions, reproducibly generate PpIX. This is of interest in various fields such as photodiagnosis, photodynamic therapy, and photobiomodulation. Use of this model organism focuses on essential mechanisms, without the complexity of a multicellular organism.

  8. 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.

  9. Bladder tissue diagnostics utilizing Protoporphyrin IX fluorescence detection

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Beyer, Wolfgang; Knuechel, Ruth; Rick, Kai; Steinbach, Pia; Kriegmair, M.

    1995-01-01

    Instillation of a solution of 5-aminolevulinic acid (5-ALA) into the urinary bladder leads to a tumorselective accumulation of fluorescing Protoporphyrin IX (PpIX) within hours. Upon fluorescence excitation using a Kr+- laser, cystoscopy provides high contrast images even of early stage tumors, that are invisible or hardly detectable by routine white light cystoscopy. Fluorescence can simply be judged by naked eyes or recorded with a target integrating camera in real color. Histological and fluorescence data of 91 patients were evaluated statistically, showing a sensitivity of 97% and a specificity of 68% for the detection of dysplastic lesions or malignant tumors. The detectability of a sufficient fluorescence contrast of suspicious versus normal tissue is not affected significantly by either short incubation times of less than 1 hour or prolonged retention times without 5-ALA in the instillation liquid of up to about 6 hours. The fluorescence intensity detected from the tissue surface is not only dependent on PpIX concentration. The additional influence of optical parameters of tissue and fluorochrome distribution on the fluorescence signal was determined using Monte Carlo computer simulations. Results show that 5-ALA induced fluorochrome detection is superior to the detection of fluorochromes that do not exclusively stain the epithelium. Using the ratio of fluorescence intensity to backscattered excitation light corrects for geometrical and absorption effects but would introduce a dependence on the scattering coefficient.

  10. Spectral action for Bianchi type-IX cosmological models

    NASA Astrophysics Data System (ADS)

    Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

    2015-10-01

    A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w 1( t) , w 2( t) , w 3( t) , and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a 0 ,a 2 ,a 4 of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki's noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

  11. Loop quantum cosmology of Bianchi IX: effective dynamics

    NASA Astrophysics Data System (ADS)

    Corichi, Alejandro; Montoya, Edison

    2017-03-01

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

  12. 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

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

    PubMed

    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

    2016-10-01

    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.

  14. Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation.

    PubMed

    Rosa-Calatrava, Manuel; Puvion-Dutilleul, Francine; Lutz, Pierre; Dreyer, Dominique; de Thé, Hugues; Chatton, Bruno; Kedinger, Claude

    2003-10-01

    The product of adenovirus type 5 (Ad5) gene IX, protein IX (pIX), is a multifunctional protein that stabilizes the viral capsid and has transcriptional activity. We show that pIX also contributes to the Ad5-induced reorganization of the host-cell nuclear ultrastructure: pIX induces the formation of specific and dynamic nuclear inclusions, and the host promyelocytic leukaemia (PML) protein, which is the main structural organizer of PML bodies, is stably relocated and confined within the pIX-induced inclusions late in infection. Our results suggest that Ad5 has evolved a unique strategy that leads to the sustained neutralization of PML bodies throughout infection, thereby ensuring optimal viral proliferation.

  15. Targeting of p53 and its homolog p73 by protoporphyrin IX.

    PubMed

    Sznarkowska, Alicja; Maleńczyk, Katarzyna; Kadziński, Leszek; Bielawski, Krzysztof P; Banecki, Bogdan; Zawacka-Pankau, Joanna

    2011-01-03

    The p53 tumor suppressor is recognized as a promising target for anti-cancer therapies. We previously reported that protoporphyrin IX (PpIX) disrupts the p53/murine double minute 2 (MDM2) complex and leads to p53 accumulation and activation of apoptosis in HCT 116 cells. Here we show the direct binding of PpIX to the N-terminal domain of p53. Furthermore, we addressed the induction of apoptosis in HCT 116 p53-null cells by PpIX and revealed interactions between PpIX and p73. We propose that PpIX disrupts the p53/MDM2 or MDMX and p73/MDM2 complexes and thereby activates the p53- or p73-dependent cancer cell death.

  16. Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation

    PubMed Central

    Rosa-Calatrava, Manuel; Puvion-Dutilleul, Francine; Lutz, Pierre; Dreyer, Dominique; De Thé, Hugues; Chatton, Bruno; Kedinger, Claude

    2003-01-01

    The product of adenovirus type 5 (Ad5) gene IX, protein IX (pIX), is a multifunctional protein that stabilizes the viral capsid and has transcriptional activity. We show that pIX also contributes to the Ad5-induced reorganization of the host-cell nuclear ultrastructure: pIX induces the formation of specific and dynamic nuclear inclusions, and the host promyelocytic leukaemia (PML) protein, which is the main structural organizer of PML bodies, is stably relocated and confined within the pIX-induced inclusions late in infection. Our results suggest that Ad5 has evolved a unique strategy that leads to the sustained neutralization of PML bodies throughout infection, thereby ensuring optimal viral proliferation. PMID:14528266

  17. 46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Adoption of section IX of the ASME Code. 57.02-2 Section... AND BRAZING General Requirements § 57.02-2 Adoption of section IX of the ASME Code. (a) The... in this part. Table 57.02-1(a)—Limitations and Modifications to the Adoption of section IX of...

  18. 46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Adoption of section IX of the ASME Code. 57.02-2 Section... AND BRAZING General Requirements § 57.02-2 Adoption of section IX of the ASME Code. (a) The... in this part. Table 57.02-1(a)—Limitations and Modifications to the Adoption of section IX of...

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

    PubMed

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

    2013-07-01

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

  20. Mg-Protoporphyrin IX Signals Enhance Plant's Tolerance to Cold Stress.

    PubMed

    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.

  1. 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.

  2. 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.

  3. The endothelial cell binding determinant of human factor IX resides in the. gamma. -carboxyglutamic acid domain

    SciTech Connect

    Toomey, J.R.; Roberts, H.R.; Stafford, D.W. ); Smith, K.J. United Blood Services, Albuquerque, NM )

    1992-02-18

    The blood coagulation factor IX(a) binds specifically to a site on endothelial cells with a K{sub d} of 2.0-3.0 nM. A number of previous studies have attempted to define the region(s) of factor IX(a) that mediate this interaction. These studies suggested that there are two regions of factor IX(a), the {gamma}-carboxyglutamic acid (Gla) domain and the epidermal growth factor like (EGF-like) domains, that mediate high-affinity binding to endothelial cells. Recently, however, the participation of the EGF1 domain has been excluded from the interaction. This indicated that if there was an EGF component of factor IX contributing to the binding affinity, then it must be in the second EGF-like domain. In order to further evaluate this relationship, the authors performed competitive binding experiments between {sup 125}I plasma factor IX and a set of six chimeric proteins composed of portions of factor VII and factor IX. The data suggest that the high-affinity interaction between factor IX and the endothelial cell binding site is mediated by the factor IX Gla domain and that the factor IX EGF domains are not involved in binding specificity.

  4. Saccharin: a Lead Compound for Structure-Based Drug Design of Carbonic Anhydrase IX Inhibitors

    PubMed Central

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

    2015-01-01

    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. PMID:25614109

  5. 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.

  6. Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

    NASA Astrophysics Data System (ADS)

    Gibbs-Strauss, Summer L.; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2008-02-01

    Aminolevulinic Acid (ALA) is a prodrug which can be administered to cells, animals or patients after which it is transformed via the Heme synthesis pathway into the fluorescent molecule Protoporphyrin IX (PpIX). PpIX has been shown to be useful as both a photosensitizer for photodynamic therapy (PDT) and as a fluorescence imaging contrast agent. The ALA-PpIX system not only provides contrast for fluorescence imaging but also gives information about the metabolic activity of the imaged tissue and thus could be useful for monitoring cancer therapy. In the current study skin photobleaching was examined to determine if PpIX fluorescence contrast in malignant brain tumors could be better visualized noninvasively. Red light photobleaching decreased skin PpIX fluorescence and increased the ability to noninvasively quantify PpIX fluorescence in murine gliomas, as in vivo measurements of mean PpIX fluorescence more closely matched ex vivo quantification following skin photobleaching. Three doses of blue light photobleaching (4 J/cm2, 8 J/cm2 and 12 J/cm2) were tested and determined to give similar levels of skin photobleaching as well as a similar window of decreased skin PpIX fluorescence for noninvasive fluorescence imaging following the photobleaching dose administration.

  7. 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

  8. 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.

  9. Ares I-X Test Flight Reference Trajectory Development

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  10. 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

  11. Effect of IX dosing on polypropylene and PVDF membrane fouling control.

    PubMed

    Myat, Darli Theint; Mergen, Max; Zhao, Oliver; Stewart, Matthew B; Orbell, John D; Merle, Tony; Croué, Jean-Philippe; Gray, Stephen

    2013-07-01

    The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA) and fluorescence spectroscopy (Method A), and UV254, organic carbon and organic nitrogen detectors (Method B), was undertaken on wastewater before and after magnetic IX treatment. Results showed partial removal of the biopolymer fraction at high IX doses. With increasing concentration of IX, evidence for nitrogen-containing compounds such as proteins and amino acids disappeared from the LC-OND chromatogram, complementary to the fluorescence response. A greater fluorescence response of tryptophan-like proteins (278 nm/343 nm) for low IX concentrations was consistent with aggregation of tryptophan-like compounds into larger aggregates, either by self-aggregation or with polysaccharides. Recycling of IX resin through multiple adsorption steps without regeneration maintained the high level of humics removal but there was no continued removal of biopolymer. Subsequent membrane filtration of the IX treated waters resulted in complex fouling trends. Filtration tests with either polypropylene (PP) or polyvinylidene fluoride (PVDF) membranes showed higher rates of initial fouling following treatment with high IX doses (10 mL/L) compared to filtration of untreated water, while treatment with lower IX doses resulted in decreased fouling rates relative to the untreated water. However, at longer filtration times the rate of fouling of IX treated waters was lower than untreated water and the relative fouling rates corresponded to the amount of biopolymer material in the feed. It was proposed that the mode of fouling changed from pore constriction during the initial filtration period to filter cake build up at longer filtration times. The organic composition strongly influenced the rate of fouling during the initial filtration period due to

  12. 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.

  13. Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton.

    PubMed

    Swiderski, R E; Solursh, M

    1992-06-01

    In this study we compare, by in situ hybridization, the spatial and temporal expression patterns of transcripts of avian type II collagen and the long and short forms of the (alpha 1) chain of type IX collagen during the development of the notochord and axial skeleton. We observed type II collagen and short form type IX collagen transcripts in the developing (stage 25-28) nonchondrogenic notochord. Conversely, long form type IX transcripts were not detectable in the notochord or perinotochordal sheath. Interestingly, all three transcripts colocalized in the developing chondrogenic vertebrae of the axial skeleton as well as in the chondrocranium and Meckel's cartilage. The expression of the short form of type IX collagen in these regions was more restricted than that of the long form. This report provides additional support for a complex regulatory pathway of cartilage marker gene expression in chondrogenic vs. nonchondrogenic tissues during avian embryogenesis.

  14. 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.

  15. 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.

  16. 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.

  17. 5-ALA/PpIX fluorescence detection of gastrointestinal neoplasia

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina G.; Vladimirov, Borislav; Terziev, Ivan; Ivanova, Radina; Avramov, Latchezar

    2009-07-01

    In the recent study delta-ALA/PpIX is used as fluorescent marker for dysplasia and tumor detection in esophagus, stomach and colon. ALA is administered per os six to eight (depending on the lesion location) hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for the LED to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to re-absorption of oxy-hemoglobin in this spectral area. Endogenous and exogenous fluorescence spectra are used to develop simple but effective algorithm, based on dimensionless ratio of the signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues. Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  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…

  19. "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…

  20. Critical Issue Bibliography (CRIB) Sheet: Title IX of the Educational Amendments of 1972.

    ERIC Educational Resources Information Center

    ERIC Clearinghouse on Higher Education, Washington, DC.

    This CRitical Issue Bibliography (CRIB) Sheet cites resources that give an overview of Title IX legislation and offer information about compliance, litigation, and related issues. Title IX of the Education Amendments of 1972 protects individuals from gender-based discrimination in education programs or activities that receive federal financial…

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

    ERIC Educational Resources Information Center

    Stader, David L.; Surface, Jeanne L.

    2014-01-01

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

  2. 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;…

  3. The Unenforced Law: Title IX Activity by Federal Agencies other than HEW. Report.

    ERIC Educational Resources Information Center

    Balles, Nancy J.

    The purposes of this report are to identify which federal agencies other than the Department of Health, Education, and Welfare have educational programs covered by Title IX; to survey those agencies to determine if they are enforcing Title IX by means of regulations, orders, or termination of funding; to identify problems of intragovernmental…

  4. 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.

  5. 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.

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

    ERIC Educational Resources Information Center

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

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

  7. 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.

  8. The product of the adenovirus intermediate gene IX is a transcriptional activator.

    PubMed Central

    Lutz, P; Rosa-Calatrava, M; Kedinger, C

    1997-01-01

    We have investigated the functional properties of the product of the adenovirus type 5 gene IX. This gene, which is expressed at intermediate times postinfection, encodes a small polypeptide (pIX) of 140 residues that has previously been shown to be incorporated into the viral capsid. Here, we show that pIX, in addition to its structural contribution, exhibits transcriptional properties. In transient transfection experiments, expression of pIX stimulated adenovirus major late promoter activity. The effect was independent of other viral proteins, but the level of promoter activation appeared strongly pIX dose dependent; similar levels of induction were observed with other cellular or viral TATA-containing (but not with TATA-less) promoters. This promoter specificity could be reproduced in a cell-free transcription system by the addition of purified recombinant pIX, further stressing the transcriptional nature of the phenomenon. A preliminary structural analysis of pIX indicated that the integrity of a putative leucine zipper at the carboxy-terminal end of the molecule, as well as elements within the amino-terminal half, was critical for pIX transcriptional activity. The relevance of these findings in adenovirus infection is discussed. PMID:9188576

  9. 40 CFR Appendix Ix to Part 266 - Methods Manual for Compliance With the BIF Regulations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Methods Manual for Compliance With the BIF Regulations IX Appendix IX to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE...

  10. 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.

  11. 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,…

  12. 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…

  13. "What do I think about Title IX?" Voices from a university community.

    PubMed

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

    2013-03-01

    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 changes it incurred. Using a gendered lens (Birrell, 2000) and qualitative interviews with 13 individuals connected to the university community, insight was gained into their perceptions of Title IX and women's and men's athletic opportunities. The theme of opportunity gained and lost was central to how these individuals perceive Title IX and resonates with the liberal (feminist) concerns out of which Title IX was born.

  14. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.

    PubMed Central

    McGraw, R A; Davis, L M; Noyes, C M; Lundblad, R L; Roberts, H R; Graham, J B; Stafford, D W

    1985-01-01

    We have independently isolated and characterized cDNA and genomic clones for the human coagulation factor IX. Sequence analysis in both cases indicates that threonine is encoded by the triplet ACT as the third residue of the activation peptide. This is in agreement with some earlier reports but in disagreement with others that show the alanine triplet GCT at this position. The discrepancy can thus be accounted for by natural variation of a single nucleotide in the normal population. Amino acid sequence analyses of activated factor IX from plasma samples of four individuals yielded two cases of alanine and two cases of threonine at the third position of the activation peptide. In factor IX from pooled plasma and in factor IX from a heterozygous individual, however, both alanine and threonine were found. Taken together, the findings show that a prevalent nondeleterious dimorphism exists in the activation peptide of human coagulation factor IX. PMID:3857619

  15. 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.

  16. 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

  17. 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.

  18. Dual-wavelength excitation for fluorescence-based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood.

    PubMed

    Hennig, Georg; Gruber, Christian; Vogeser, Michael; Stepp, Herbert; Dittmar, Stephan; Sroka, Ronald; Brittenham, Gary M

    2014-07-01

    Quantification of erythrocyte zinc protoporphyrin IX (ZnPP) and protoporphyrin IX (PPIX), individually or jointly, is useful for the diagnostic evaluation of iron deficiency, iron-restricted erythropoiesis, lead exposure, and porphyrias. A method for simultaneous quantification of ZnPP and PPIX in unwashed blood samples is described, using dual-wavelength excitation to effectively eliminate background fluorescence from other blood constituents. In blood samples from 35 subjects, the results of the dual-wavelength excitation method and a reference high performance liquid chromatography (HPLC) assay were closely correlated both for ZnPP (rs = 0.943, p < 0.0001; range 37-689 μmol ZnPP/mol heme, 84-1238 nmol/L) and for PPIX (rs = 0.959, p < 0.0001; range 42-4212 μmol PPIX/mol heme, 93-5394 nmol/L). In addition, for ZnPP, the proposed method is compared with conventional single-wavelength excitation and with commercial front-face fluorimetry of washed erythrocytes and whole blood. We hypothesize that dual-wavelength excitation fluorimetry will provide a new approach to the suppression of background fluorescence in blood and tissue measurements of ZnPP and PPIX.

  19. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

    PubMed Central

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

    2014-01-01

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

  20. Recent Developments in Targeting Carbonic Anhydrase IX for Cancer Therapeutics

    PubMed Central

    McDonald, Paul C.; Winum, Jean-Yves; Supuran, Claudiu T.; Dedhar, Shoukat

    2012-01-01

    Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness. Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecule inhibitors, consequently disrupting pH regulation by cancer cells, has been shown recently to impair primary tumor growth and metastasis. Many of these agents are in preclinical or clinical development and constitute a novel, targeted strategy for cancer therapy. PMID:22289741

  1. 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

  2. Protoporphyrin IX: the Good, the Bad, and the Ugly

    PubMed Central

    Sachar, Madhav; Anderson, Karl E.

    2016-01-01

    Protoporphyrin IX (PPIX) is ubiquitously present in all living cells in small amounts as a precursor of heme. PPIX has some biologic functions of its own, and PPIX-based strategies have been used for cancer diagnosis and treatment (the good). PPIX serves as the substrate for ferrochelatase, the final enzyme in heme biosynthesis, and its homeostasis is tightly regulated during heme synthesis. Accumulation of PPIX in human porphyrias can cause skin photosensitivity, biliary stones, hepatobiliary damage, and even liver failure (the bad and the ugly). In this work, we review the mechanisms that are associated with the broad aspects of PPIX. Because PPIX is a hydrophobic molecule, its disposition is by hepatic rather than renal excretion. Large amounts of PPIX are toxic to the liver and can cause cholestatic liver injury. Application of PPIX in cancer diagnosis and treatment is based on its photodynamic effects. PMID:26588930

  3. 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.

  4. MYStIX: Dynamical evolution of young clusters

    NASA Astrophysics Data System (ADS)

    Kuhn, Michael A.

    2014-08-01

    The spatial structure of young stellar clusters in Galactic star-forming regions provides insight into these clusters’ dynamical evolution---a topic with implications for open questions in star-formation and cluster survival. The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) provides a sample of >30,000 young stars in star-forming regions (d<3.6 kpc) that contain at least one O-type star. We use the finite mixture model analysis to identify subclusters of stars and determine their properties: including subcluster radii, intrinsic numbers of stars, central density, ellipticity, obscuration, and age. In 17 MYStIX regions we find 142 subclusters, with a diverse radii and densities and age spreads of up to ~1 Myr in a region. There is a strong negative correlation between subcluster radius and density, which indicates that embedded subclusters expand but also gain stars as they age. Subcluster expansion is also shown by a positive radius--age correlation, which indicates that subclusters are expanding at <1 km/s. The subcluster ellipticity distribution and number--density relation show signs of a hierarchical merger scenario, whereby young stellar clusters are built up through mergers of smaller clumps, causing evolution from a clumpy spatial distribution of stars (seen in some regions) to a simpler distribution of stars (seen in other regions). Many of the simple young stellar clusters show signs of dynamically relaxation, even though they are not old enough for this to have occurred through two-body interactions. However, this apparent contradiction might be explained if small subcluster, which have shorter dynamical relaxation times, can produce dynamically relaxed clusters through hierarchical mergers.

  5. 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.

  6. 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.

  7. 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

    2016-04-07

    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.

  8. 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

  9. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

    PubMed Central

    Negrier, Claude; Klamroth, Robert; Tiede, Andreas; Pabinger-Fasching, Ingrid; Voigt, Christine; Jacobs, Iris; Morfini, Massimo

    2012-01-01

    A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440. PMID:22859609

  10. The use of CA-IX as a diagnostic method for oral leukoplakia.

    PubMed

    Pérez-Sayáns, M; Suárez-Peñaranda, J M; Torres-López, M; Supuran, C T; Gándara-Vila, P; Gayoso-Diz, P; Barros-Angueira, F; Gallas-Torreira, M; García-García, A

    2015-02-01

    The presence and degree of dysplasia are important diagnostic and prognostic criteria for oral leukoplakia, but evaluation of dysplasia is difficult and subjective. Carbonic anhydrase-IX (CA-IX) is expressed primarily in tumor cells and is considered a specific hypoxia marker. We investigated the role of CA-IX in oral leukoplakia. We investigated 30 specimens of oral leukoplakia and 35 dysplasia specimens adjacent to the tumor margin. We analyzed clinical variables including age, sex, degree of dysplasia, and smoking, clinical appearance of leukoplakia, number of lesions, location, size, clinical monitoring, malignant transformation and recurrence. For the immunohistochemical study, we used a noncommercial monoclonal antibody against human CA-IX MAb M75. We found greater CA-IX positivity in nonsmokers, erythroplakia and mottled leukoplakia, those located on the tongue, patients with multiple lesions, 2-4 cm leukoplakias and in recurrent cases, although differences were not statistically significant. All lesions in all samples without dysplasia were negative for CA-IX; however, for all other categories of dysplasia, the percentages of positivity and negativity varied. Regarding the diagnostic index values, we found a sensitivity of 32%, specificity of 100%, a positive predictive value of 100% and a negative predictive value of 13%. Leukoplakias appear mainly in females and potentially are malignant; more than 90% have some degree of dysplasia, and therefore require close clinical and histopathological monitoring. The CA-IX immunohistochemical marker may be useful for screening samples without dysplasia owing to its high specificity.

  11. 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.

  12. 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.

  13. Photosensitizing effect of hematoporphyrin IX on immature stages of Ceratitis capitata (Diptera: Tephritidae).

    PubMed

    Pujol-Lereis, Luciana Mercedes; Massaldi, Ana; Rabossi, Alejandro; Quesada-Allué, Luis Alberto

    2010-01-01

    Immature stages of Ceratitis capitata were tested as a model for hematoporphyrin IX (HP IX) phototoxicity. The lethal concentration 50 (LC(50)) of HP IX in the food was determined during postembryonic development until adult emergence as 0.173 mm (95% CI: 0.138-0.209). The corresponding HP IX LC(50) during the dispersal period alone was 0.536 mm (95% CI: 0.450-0.633). HP IX toxicity was compared against Phloxine B (PhB) (0.5 mm). HP IX elicited a mortality of 90.87%, which was mainly concentrated during prepupal and early pupal stages. PhB mortality was much lower (56.88%) and occurred mainly during the adult pharate stage. A direct correlation between light-dependent HP IX mortality, evidence of reactive oxygen species (ROS) and lipid peroxidation (conjugated dienes and thiobarbituric acid reactive substances) was established in C. capitata larvae. ROS were found to be very significant in both the brain and in the gut.

  14. Catalytic activity of human carbonic anhydrase isoform IX is displayed both extra- and intracellularly.

    PubMed

    Klier, Michael; Jamali, Somayeh; Ames, Samantha; Schneider, Hans-Peter; Becker, Holger M; Deitmer, Joachim W

    2016-01-01

    Most carbonic anhydrases catalyse the reversible conversion of carbon dioxide to protons and bicarbonate, either as soluble cytosolic enzymes, in or at intracellular organelles, or at the extracellular face of the cell membrane as membrane-anchored proteins. Carbonic anhydrase isoform IX (CA IX), a membrane-bound enzyme with catalytic activity at the extracellular membrane surface, has come to prominence in recent years because of its association with hypoxic tissue, particularly tumours, often indicating poor prognosis. We have evaluated the catalytic activity of CA IX heterologously expressed in Xenopus laevis oocytes by measuring the amplitude and rate of cytosolic pH changes as well as pH changes at the outer membrane surface (pHs ) during addition and removal of 5% CO2 /25 mm HCO3-, and by mass spectrometry. Our results indicate both extracellular and intracellular catalytic activity of CA IX. Reduced rates of CO2 -dependent intracellular pH changes after knockdown of CA IX confirmed these findings in two breast cancer cell lines: MCF-7 and MDA-MB-231. Our results demonstrate a new function of CA IX that may be important in the search for therapeutic cancer drugs targeting CA IX.

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

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

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

  16. 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.

  17. Ares I-X Flight Test Vehicle similitude to the Ares I Crew Launch Vehicle

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  18. 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.

  19. 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.

  20. 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.

  1. Uptake of topically applied 5-aminolevulinic acid and production of protoporphyrin IX in normal mouse skin: dependence on skin temperature.

    PubMed

    Juzenas, P; Sørensen, R; Iani, V; Moan, J

    1999-04-01

    The temperature dependence of the uptake phase of 5-aminolevulinic acid (ALA) and the following production phase of protoporphyrin IX (PpIX) in normal mouse skin was investigated. A cream containing 20% ALA was topically applied on the skin for 10 min. The amount of ALA-induced PpIX was evaluated by measuring the fluorescence of PpIX from the treated skin. No measurable amount of PpIX was found in the skin immediately after 10 min application of ALA. The penetration of ALA into the skin was almost temperature independent while the following production of PpIX was found to be a strongly temperature-dependent process. Practically no PpIX was formed in the skin as long as skin temperature was kept low (12 degrees C).

  2. Identification of the molecular defect in factor IX Chapel Hill: substitution of histidine for arginine at position 145.

    PubMed Central

    Noyes, C M; Griffith, M J; Roberts, H R; Lundblad, R L

    1983-01-01

    Hemophilia B Chapel Hill is a mild hereditary hemorrhagic disorder in which the factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced. Previous studies have demonstrated that purified factor IX Chapel Hill has 8% of the activity of normal human factor IX and that the activation of factor IX Chapel Hill is defective in that only one of the two peptide bonds hydrolyzed during activation of normal factor IX is cleaved. The tryptic peptides from normal human factor IX and factor IX Chapel Hill were subjected to analysis by high-performance liquid chromatography. Comparison of the elution profile of the peptides obtained from factor IX Chapel Hill and normal factor IX demonstrated that the tripeptide Leu-Thr-Arg, which is derived from the normal molecule (positions 143-145) immediately amino-terminal from the Arg-Ala peptide bond at 145-146 that is cleaved during the activation of factor IX with factor XIa, was absent in the digest obtained from factor factor IX Chapel Hill. The elongated "activation peptide" from factor factor IX Chapel Hill was obtained by further high-performance liquid chromatographic fractionation and subjected to primary structure analysis. The following sequence, corresponding to positions 143-147, was obtained: Leu-Thr-His-Ala-Glu. Thus, the primary molecular defect in factor factor IX Chapel Hill is the substitution of histidine for arginine at position 145. This substitution precludes cleavage by factor XIa at this peptide bond, and the activation peptide region remains associated with the light chain of factor IXa Chapel Hill. PMID:6603618

  3. 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.

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

    NASA Technical Reports Server (NTRS)

    Ryan, M. P., Jr.

    1971-01-01

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

  5. Comparative effectiveness of clinically used light sources for cutaneous protoporphyrin IX-based photodynamic therapy.

    PubMed

    Sayre, Robert M; Dowdy, John C; Gottschalk, Ronald W

    2011-04-01

    This report documents the optical characteristics of a number of photodynamic therapy (PDT) light sources of varied types, measured and indexed relative to estimated effectiveness for activation of the PDT chromaphore protoporphyrin IX (PpIX). PDT sources in use at several clinics, including intense pulsed light (IPL) sources, lasers, and continuous wave (CW) light sources, were spectroradiometrically measured and indexed relative to their overlap to an absorption spectrum of PpIX. The sources were highly disparate, varying in power from irradiance in the mW/cm(2) range for the CW sources up to ∼30 J/cm(2) per flash for the IPL sources. Our PpIX Index ranged by a factor of nearly 100 (0.008-0.630) in estimated PpIX PDT effectiveness following the distinct spectral characteristics of the light sources surveyed. Application of this PpIX Index, tempered with an understanding of the biology of the lesion being treated and effective spectrum of the light source reaching the lesion requiring therapy, provides a rational algorithm to approximate equivalent light doses prior to clinical protocols to establish equivalent patient outcomes employing alternative PDT light sources.

  6. Identification of a juxtamembrane mechanosensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex

    PubMed Central

    Zhang, Wei; Deng, Wei; Zhou, Liang; Xu, Yan; Yang, Wenjun; Liang, Xin; Wang, Yizhen; Kulman, John D.; Zhang, X. Frank

    2015-01-01

    How glycoprotein (GP)Ib-IX complex on the platelet surface senses the blood flow through its binding to the plasma protein von Willebrand factor (VWF) and transmits a signal into the platelet remains unclear. Here we show that optical tweezer-controlled pulling of the A1 domain of VWF (VWF-A1) on GPIb-IX captured by its cytoplasmic domain induced unfolding of a hitherto unidentified structural domain before the dissociation of VWF-A1 from GPIb-IX. Additional studies using recombinant proteins and mutant complexes confirmed its existence in GPIb-IX and enabled localization of this quasi-stable mechanosensitive domain of ∼60 residues between the macroglycopeptide region and the transmembrane helix of the GPIbα subunit. These results suggest that VWF-mediated pulling under fluid shear induces unfolding of the mechanosensitive domain in GPIb-IX, which may possibly contribute to platelet mechanosensing and/or shear resistance of VWF-platelet interaction. The identification of the mechanosensitive domain in GPIb-IX has significant implications for the pathogenesis and treatment of related blood diseases. PMID:25359992

  7. 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.

  8. Factor IX gene analysis in 70 unrelated patients with haemophilia B: description of 13 new mutations.

    PubMed

    Attali, O; Vinciguerra, C; Trzeciak, M C; Durin, A; Pernod, G; Gay, V; Ménart, C; Sobas, F; Dechavanne, M; Négrier, C

    1999-11-01

    Seventy unrelated patients suffering from haemophilia B have been screened for determining the molecular defect and for evaluating the spectrum of factor IX mutations in the Rhône Alpes region in France. Most patients were characterized with respect to factor IX antigen and factor IX coagulant activity. We have used denaturing gradient gel electrophoresis to obtain a full scanning of the whole coding, promoter, and exon flanking sequences of the factor IX gene. This technique enabled us to determine the molecular defect in 68 out of 70 families (97%), and the mutation was further identified in the two last patients with a direct sequencing of the gene. A total of 2 complete gene deletions in patients with antifactor IX inhibitor, 6 small insertions/deletions and 62 point mutations were found. Two of these nucleotide substitutions (Arg145His and Ala233Thr) were detected in 21 patients (30%) suggesting the existence of a local founder effect. Thirteen mutations were previously undescribed, including 7 missense mutations. The detection of mutations in patients affected with haemophilia B may shed some light in the structure-function relationship of factor IX molecule within the coagulation system.

  9. 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.

  10. 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.

  11. 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

  12. Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker.

    PubMed

    Nascimento da Silva, Monica; Sicchieri, Letícia Bonfante; de Oliveira Silva, Flávia Rodrigues; Andrade, Maira Franco; Courrol, Lilia Coronato

    2014-03-21

    Protoporphyrin IX (PPIX), a derivative of hematoporphyrin, can accumulate in rapidly growing tissues, including tumors and atherosclerotic plaques. The objective of this study is to employ PPIX fluorescence to detect the changes in blood caused by the formation of atheromatous plaques in arteries; this measurement can function as a liquid biopsy. For this purpose twenty four rabbits were randomly divided into groups: control group (CG)--fed with a normal diet, and an experimental group (EG)--fed with a hypercholesterolemic diet (1% cholesterol). Blood samples were collected before (0 time) and after 22, 43, 64 days to measure biochemical factors. The aortas were removed after 22, 43 and 64 days to assess the atherosclerotic plaques. PPIX was extracted from the blood and fluorescence was measured in the 550-750 nm range from samples that were excited at 405 nm. Aminolevulinic acid (ALA) was administered intravenously to increase the PPIX fluorescence intensity in the arteries and consequently in the liquid biopsy of the atherosclerotic plaques. The results have shown that the PPIX fluorescence increased as the atheromatous plaques grew. The aorta fluorescence and the PPIX fluorescence increased in the animals in the experimental group that received ALA. PPIX that accumulates in atheromatous plaques transfers to the blood and can be analyzed by extracting porphyrin from total blood. Therefore, this method can aid in the early diagnosis of atherosclerosis with high sensitivity.

  13. 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.

  14. 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.

  15. Reconstruction of Ares I-X Integrated Vehicle Rollout Loads

    NASA Technical Reports Server (NTRS)

    Chamberlain, Matthew K.; Hahn, Steven R.

    2011-01-01

    The measurements taken during the Ares I-X test flight provided a unique opportunity to assess the accuracy of the models and methods used to analyze the loads and accelerations present in the planned Ares I vehicle. During the rollout of the integrated vehicle from the Vehicle Assembly Building (VAB) to the launch pad, the vehicle and its supporting structure are subjected to wind loads and the vibrations produced by the crawler-transporter (CT) that is carrying it. While the loads induced on the vehicle during this period are generally low relative to those experienced in flight, the rollout is a period of operation of primary interest to those designing both the ground support equipment and the interfaces between the launch vehicle and its supporting structure. In this paper, the methods used for reconstructing the loads during the rollout phase are described. The results generated are compared to measured values, leading to insight into the accuracy of the Ares I assessment techniques.

  16. 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.

  17. Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer

    PubMed Central

    Brown-Glaberman, Ursa; Marron, Marilyn; Chalasani, Pavani; Livingston, Robert; Iannone, Maria; Specht, Jennifer; Stopeck, Alison T.

    2016-01-01

    Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p = 0.02) but not AC (p = 0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy. PMID:26941473

  18. 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.

  19. 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.

  20. Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.

    PubMed

    Genis, Caroli; Sippel, Katherine H; Case, Nicolette; Cao, Wengang; Avvaru, Balendu Sankara; Tartaglia, Lawrence J; Govindasamy, Lakshmanan; Tu, Chingkuang; Agbandje-McKenna, Mavis; Silverman, David N; Rosser, Charles J; McKenna, Robert

    2009-02-17

    Recently, a convincing body of evidence has accumulated suggesting that the overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to the acidification of the extracellular matrix, which in turn promotes the growth and metastasis of the tumor. These observations have made CA IX an attractive drug target for the selective treatment of certain cancers. Currently, there is no available X-ray crystal structure of CA IX, and this lack of availability has hampered the rational design of selective CA IX inhibitors. In light of these observations and on the basis of structural alignment homology, using the crystal structure of carbonic anhydrase II (CA II) and the sequence of CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by Gln has been constructed to resemble the active site of CA IX. This CA IX mimic has been characterized kinetically using (18)O-exchange and structurally using X-ray crystallography, alone and in complex with five CA sulfonamide-based inhibitors (acetazolamide, benzolamide, chlorzolamide, ethoxzolamide, and methazolamide), and compared to CA II. This structural information has been evaluated by both inhibition studies and in vitro cytotoxicity assays and shows a correlated structure-activity relationship. Kinetic and structural studies of CA II and CA IX mimic reveal chlorzolamide to be a more potent inhibitor of CA IX, inducing an active-site conformational change upon binding. Additionally, chlorzolamide appears to be cytotoxic to prostate cancer cells. This preliminary study demonstrates that the CA IX mimic may provide a useful model to design more isozyme-specific CA IX inhibitors, which may lead to development of new therapeutic treatments of some cancers.

  1. 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

  2. Protoporphyrin IX Content Correlates with Activity of Photobleaching Herbicides

    PubMed Central

    Becerril, Jose M.; Duke, Stephen O.

    1989-01-01

    Several laboratories have demonstrated recently that photobleaching herbicides such as acifluorfen and oxadiazon cause accumulation of protoporphyrin IX (PPIX), a photodynamic pigment capable of herbicidal activity. We investigated, in acifluorfen-treated tissues, the in vivo stability of PPIX, the kinetics of accumulation, and the correlation between concentration of PPIX and herbicidal damage. During a 20 hour dark period, PPIX levels rose from barely detectable concentrations to 1 to 2 nanomoles per 50 cucumber (Cucumis sativus L.) cotyledon discs treated with 10 micromolar acifluorfen. When placed in 500 micromoles per square meter per second PAR, PPIX levels decayed logarithmically, with an initial half-life of about 2.5 hours. PPIX levels at each time after exposure to light correlated positively with the cellular damage that occurred during the following 1 hour in both green and yellow (tentoxin-treated) cucumber cotyledon tissues. PPIX levels in discs incubated for 20 hours in darkness correlated positively with the acifluorfen concentration in which they were incubated. In cucumber, the level of herbicidal damage caused by several p-nitrodiphenyl other herbicides, a p-chlorodiphenylether herbicide, and oxadiazon correlated positively with the amount of PPIX induced to accumulate by each of the herbicide treatments. Similar results were obtained with acifluorfen-treated pigweed and velvetleaf primary leaf tissues. In cucumber, PPIX levels increased within 15 and 30 minutes after exposure of discs to 10 micromolar acifluorfen in the dark and light, respectively. These data strengthen the view that PPIX is responsible for all or a major part of the photobleaching activity of acifluorfen and related herbicides. PMID:16666869

  3. 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.

  4. 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

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

    PubMed Central

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

    2013-01-01

    Abstract. Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025  μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations. PMID:23584445

  6. 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

  7. [Fluorescence spectrum analysis system for protoporphyrin IX in serum based on wavelet transform].

    PubMed

    Zhu, Dian-ming; Yang, Hong-peng; Luo, Xiao-sen; Liu, Ying; Shen, Zhong-hua; Lu, Jian; Ni, Xiao-wu

    2007-12-01

    Protoporphyrin IX is an important kind of organic compound for vital movement, and can be used as the sign of tumour blood. Human protoporphyrin IX content in serum is very low, and affected by various factors. The serum fluorescence spectrum analysis system based on wavelet transform was used to discriminated the protoporphyrin IX weak signals. The protoporphyrin IX fluorescence spectrum was obtained by a multi-function spectrum measuring system, and decomposed several times by wavelet transform to distinguish the noise and spectrum signals. The fluorescence spectrum can be divided into corresponding discrete approximations signals (a1-a6) and discrete details signals (d1-d6) by six times of decomposition, showing the signal frequency decreasing with decomposition times increasing and the protoporphyrin IX fluorescence character peak appears here. The weak signals were discriminated and the exactly component and quantity can be acquired for further analysis. So it can be analysed quantitatively. The researches in the present paper provide the potential application in the diagnosis of incipient tumous using the serum fluorescence spectrum

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  9. Clearance of protoporphyrin IX induced by 5-aminolevulinic acid from WiDr human colon carcinoma cells

    NASA Astrophysics Data System (ADS)

    Juzeniene, Asta; Kaliszewski, Miron; Bugaj, Andrzej; Moan, Johan

    2009-06-01

    5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is the most widely practiced form of PDT in dermatology. One of the advantages of ALA-PDT is that undesirable photosensitization lasts only for 24-48 h. In order to optimize ALA-PDT it is necessary to understand the mechanisms controlling intracellular PpIX clearance (efflux and transformation into heme) in order to decrease protoporphyrin IX (PpIX) clearance rates in the early stages of its production. The aim of this study was to investigate the factors controlling the clearance of intracellular PpIX. Fluorescence spectroscopy was used to study PpIX kinetics in WiDr cells initially treated with ALA. The clearance rate of PpIX in WiDr cells was faster after application of a low concentration of ALA (0.1 mM) than after application of high concentration of ALA (1 mM). PpIX was cleared faster from cells which initially were seeded at low densities than cells seeded at higher densities. The presence of the iron chelator deferoxamine reduced the clearance rate of PpIX, while the presence of ferrous sulfate acted oppositely. The decay rate of PpIX in WiDr cells was faster at higher temperature than at lower. The ferrochelatase activity at pH 7.2 was significantly greater than that at pH 6.7. ALA concentration, application time, cell density, temperature, pH, intracellular iron content, intracellular amount and localization of PpIX are factors controlling PpIX clearance.

  10. Her2 oncogene transformation enhances 5-aminolevulinic acid-mediated protoporphyrin IX production and photodynamic therapy response

    PubMed Central

    Yang, Xue; Palasuberniam, Pratheeba; Myers, Kenneth A.; Wang, Chenguang; Chen, Bin

    2016-01-01

    Enhanced protoporphyrin IX (PpIX) production in tumors derived from the administration of 5-aminolevulinic acid (ALA) enables the use of ALA as a prodrug for photodynamic therapy (PDT) and fluorescence-guided tumor resection. Although ALA has been successfully used in the clinic, the mechanism underlying enhanced ALA-induced PpIX production in tumors is not well understood. Human epidermal growth receptor 2 (Her2, Neu, ErbB2) is a driver oncogene in human cancers, particularly breast cancers. Here we showed that, in addition to activating Her2/Neu cell signaling, inducing epithelial-mesenchymal transition and upregulating glycolytic enzymes, transfection of NeuT (a mutated Her2/Neu) oncogene in MCF10A human breast epithelial cells significantly enhanced ALA-induced PpIX fluorescence by elevating some enzymes involved in PpIX biosynthesis. Furthermore, NeuT-transformed and vector control cells exhibited drastic differences in the intracellular localization of PpIX, either produced endogenously from ALA or applied exogenously. In vector control cells, PpIX displayed a cell contact-dependent membrane localization at high cell densities and increased mitochondrial localization at low cell densities. In contrast, no predominant membrane localization of PpIX was observed in NeuT cells and ALA-induced PpIX showed a consistent mitochondrial localization regardless of cell density. PDT with ALA caused significantly more decrease in cell viability in NeuT cells than in vector cells. Our data demonstrate that NeuT oncogene transformation enhanced ALA-induced PpIX production and altered PpIX intracellular localization, rendering NeuT-transformed cells increased response to ALA-mediated PDT. These results support the use of ALA for imaging and photodynamic targeting Her2/Neu-positive tumors. PMID:27527860

  11. Monoclonal antibody against chicken type IX collagen: preparation, characterization, and recognition of the intact form of type IX collagen secreted by chondrocytes.

    PubMed

    Irwin, M H; Silvers, S H; Mayne, R

    1985-09-01

    A series of monoclonal antibodies was prepared against the pepsin-resistant fragment of type IX collagen designated HMW. One of these antibodies (called 2C2) was selected for further analysis. Antibody 2C2 showed no cross-reactivity with other collagen types by inhibition enzyme-linked immunosorbent assays. It recognized an epitope present in native HMW, but failed to recognize any of the three chains of HMW fractionated after denaturation followed by reduction and alkylation of interchain disulfide bridges. Electron microscopic observations after rotary shadowing showed that the location of the epitope for antibody 2C2 was close to the carboxy-terminus of HMW. Immunofluorescent staining of sections of embryonic and adult cartilage with antibody 2C2 after removal of proteoglycans by testicular hyaluronidase digestion showed that type IX collagen is distributed throughout the cartilage matrix, and is not present in other connective tissues or skeletal muscle. The intact type IX collagen molecule, which was secreted by a suspension culture of freshly isolated embryonic chick chondrocytes, was recognized by rotary shadowing in the presence of antibody 2C2 after first precipitating the procollagens from the culture medium with ammonium sulfate (30%). Two different collagenous molecules were present in the precipitate: a longer molecule of type II procollagen (average length, 335 nm) with both amino- and carboxy-propeptides still remaining uncleaved, and a shorter molecule (average length, 190 nm) which was identified as type IX collagen. Antibody 2C2 consistently bound to the shorter molecules at a site located 136 nm from a distinctive knob at one end of the molecule, and did not bind to any specific site on the type II procollagen molecules. The structure of the intact type IX collagen molecule with the location of both collagenous and noncollagenous domains was as predicted after converting the nucleotide sequence of a cDNA clone encoding for one of the chains of

  12. 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

  13. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with secondary sulfonamides incorporating benzothiazole scaffolds.

    PubMed

    Petrou, Anthi; Geronikaki, Athina; Terzi, Emine; Guler, Ozen Ozensoy; Tuccinardi, Tiziano; Supuran, Claudiu T

    2016-12-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of benzothiazole-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I and hCA II and the transmembrane hCA IX and hCA XII. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting hCA IX and hCA XII over the off-target ones hCA I and hCA II. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.

  14. Spectroscopic study of protoporphyrin IX zinc(II) encapsulated in sol-gel glass.

    PubMed

    Zaitoun, Mohammed A

    2005-06-01

    Previous studies indicated that the organization of native porphyrins and their intentionally designated derivatives in solid substrates is of current interest because of the biological and practical importance of these compounds. In this paper, we report herein for the first time the incorporation of a functionalized diacid, protoporphyrin IX Zn(II) (Zn-pp-IX), successfully in a silica based transparent organic-inorganic hybrid material by choosing proper alkoxy silane containing amino-group via the sol-gel method. The entrapped guest was diagnosed using UV-vis sectrophotometry, emission spectroscopy, and infrared spectrometry; the properties of the encapsulated porphyrin were compared to those of the compound in solution. The results indicate that Zn-pp-IX is well distributed and homogeneously in the glass.

  15. Loop quantum cosmology of Bianchi IX: Inclusion of inverse triad corrections

    NASA Astrophysics Data System (ADS)

    Corichi, Alejandro; Karami, Asieh

    2016-06-01

    We consider the loop quantization of the (diagonal) Bianchi type IX cosmological model. We explore different quantization prescriptions that extend the work of Wilson-Ewing and Singh. In particular, we study two different ways of implementing the so-called inverse triad corrections. We construct the corresponding Hamiltonian constraint operators and show that the singularity is formally resolved. We find the effective equations associated with the different quantization prescriptions, and study the relation with the isotropic k = 1 model that, classically, is contained within the Bianchi IX model. Somewhat surprisingly, we find the most natural quantization does not reduce to the k = 1 model. We use geometrically defined scalar observables to explore the physical implications of each of these theories. This is the first part in a series of papers analyzing different aspects of the Bianchi IX model, with inverse corrections, within loop quantum cosmology (LQC).

  16. 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.

  17. 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.

  18. Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion.

    PubMed

    Feghhi, Shirin; Munday, Adam D; Tooley, Wes W; Rajsekar, Shreya; Fura, Adriane M; Kulman, John D; López, Jose A; Sniadecki, Nathan J

    2016-08-09

    Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIbα and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIbα and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIbα are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.

  19. 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.

  20. 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.

  1. [Identification of protoporphyrin IX fluorescence spectrum in human blood serum by biorthogonal spline wavelet].

    PubMed

    Zhu, Dian-ming; Jin, Wan-xiang; Luo, Xiao-sen; Liu, Ying; Shen, Zhong-hua; Lu, Jian; Ni, Xiao-wu

    2008-08-01

    For the low content and weak fluorescence intensity, usually presenting shoulder peaks, it is often hard to locate protoporphyrin IX and identify its fluorescence intensity in human blood serum. Biorthogonal spline wavelet may work for the identification of its weak signal Superimposing protoporphyrin IX fluorescence signal on the background of blood serum spectrum, a series of varied fluorescence spectra of them can be obtained. The protoporphyrin IX fluorescence signal from blood serum background is separated and the fluorescence spectrum can be divided into corresponding discrete approximate signals (a1-a7) and discrete details signals (d1-d7) by biorthogonal spline wavelet bior 5.5 seven levels decomposition. The signal frequency shows a gradual decrease with increasing decomposition. Protoporphyrin IX fluorescence peak emerges when it comes to the 7th decomposition. The signal peak shifts about 2.5 mm downwards as the signal intensity decreases, whereas the signal peak from wavelet filter remains where it was. As the synchronization disappears between signal intensity and signal peak, usually it is hard to assure the fluorescence intensity and peak location. However, signal from wavelet filter may ignore the affect and identify the protoporphyrin IX in human blood serum with the help of biorthogonal spline wavelet. As the linear alternation of wavelet and discrete details signals maintain their inborn linear relations, the authors can carry out the qualitative and quantitative analysis for the precise content and quantity of protoporphyrin IX in blood serum, which provides a feasible method for the application of blood serum fluorescence spectrum to tumor early diagnosis.

  2. Toxoplasma gondii AP2IX-4 Regulates Gene Expression during Bradyzoite Development.

    PubMed

    Huang, Sherri; Holmes, Michael J; Radke, Joshua B; Hong, Dong-Pyo; Liu, Ting-Kai; White, Michael W; Sullivan, William J

    2017-01-01

    Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. Knockout of AP2IX-4 had no discernible effect on tachyzoite replication but resulted in a reduced frequency of tissue cyst formation following alkaline stress induction-a defect that is reversible by complementation. AP2IX-4 has a complex role in regulating bradyzoite gene expression, as the levels of many bradyzoite mRNAs dramatically increased beyond those seen under conditions of normal stress induction in AP2IX-4 knockout parasites exposed to alkaline media. The loss of AP2IX-4 also resulted in a modest virulence defect and reduced cyst burden in chronically infected mice, which was reversed by complementation. These findings illustrate that the transcriptional mechanisms responsible for tissue cyst development operate across the intermediate life cycle from the dividing tachyzoite to the dormant bradyzoite. IMPORTANCEToxoplasma gondii is a single-celled parasite that persists in its host as a transmissible tissue cyst. How the parasite converts from its replicative form to the bradyzoites housed in tissue cysts is not well understood, but the process clearly involves changes in gene expression. Here we report that parasites lacking a cell cycle-regulated transcription factor called AP2IX-4 display reduced frequencies of tissue cyst formation in culture and

  3. 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

  4. Toxoplasma gondii AP2IX-4 Regulates Gene Expression during Bradyzoite Development

    PubMed Central

    Huang, Sherri; Holmes, Michael J.; Radke, Joshua B.; Hong, Dong-Pyo; Liu, Ting-Kai; White, Michael W.

    2017-01-01

    ABSTRACT Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. Knockout of AP2IX-4 had no discernible effect on tachyzoite replication but resulted in a reduced frequency of tissue cyst formation following alkaline stress induction—a defect that is reversible by complementation. AP2IX-4 has a complex role in regulating bradyzoite gene expression, as the levels of many bradyzoite mRNAs dramatically increased beyond those seen under conditions of normal stress induction in AP2IX-4 knockout parasites exposed to alkaline media. The loss of AP2IX-4 also resulted in a modest virulence defect and reduced cyst burden in chronically infected mice, which was reversed by complementation. These findings illustrate that the transcriptional mechanisms responsible for tissue cyst development operate across the intermediate life cycle from the dividing tachyzoite to the dormant bradyzoite. IMPORTANCE Toxoplasma gondii is a single-celled parasite that persists in its host as a transmissible tissue cyst. How the parasite converts from its replicative form to the bradyzoites housed in tissue cysts is not well understood, but the process clearly involves changes in gene expression. Here we report that parasites lacking a cell cycle-regulated transcription factor called AP2IX-4 display reduced frequencies of tissue cyst formation in

  5. 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

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

    PubMed

    Chen, Qiuying; Hirsch, Rhoda Elison

    2006-03-01

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

  7. "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…

  8. Perceptions of Title IX's Impact on Gender Equity within Intercollegiate Athletics: The Mississippi Public Community and Junior Colleges

    ERIC Educational Resources Information Center

    Van Daniel, Roderick

    2012-01-01

    Title IX's legislation has been in place since 1972 and has affected female participation in a positive form towards gender equity. However many institution sill have difficulty complying with the standards mandated by Title IX. Gender equity is established by meeting substantial proportionality, continued expansion, or full accommodations prongs…

  9. Title IX Program Evaluation: Corresponding with FY 98 Application for Grants. Albuquerque Public Schools, 1997-98.

    ERIC Educational Resources Information Center

    Mearns, Curt

    Title IX and Johnson O'Malley services were provided to 1,495 Native American students at 10 Albuquerque (New Mexico) elementary, middle, and high schools and the Homework Center during the 1997-98 school year. The five goals of the Title IX program were to provide: (1) intervention assistance for students, in which students, parents, and staff…

  10. 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

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Terms relating to other entities and concepts... 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. 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.

  12. 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.... 268, App. IX Appendix IX to Part 268—Extraction Procedure (EP) Toxicity Test Method and Structural... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11...

  13. Protoporphyrin IX Functionalised AgSiO2 Core-shell Nanoparticle: Plasmonic Enhancement of Fluorescence and Singlet Oxygen Production.

    PubMed

    Lismont, Marjorie; Dreesen, Laurent; Heinrichs, Benoît; Páez, Carlos A

    2015-12-15

    Metal-enhanced processes arising from the coupling of a dye with metallic nanoparticles (NPs) have been widely reported. However, few studies have simultaneously investigated these mechanisms from the viewpoint of dye fluorescence and photoactivity. Herein, protoporphyrin IX (PpIX) is grafted onto the surface of silver core silica shell NPs in order to investigate the effect of silver (Ag) localised surface plasmon resonance (LSPR) on PpIX fluorescence and PpIX singlet oxygen ((1) O2 ) production. Using two Ag core sizes, we report a systematic study of these photophysical processes as a function of silica (SiO2 ) spacer thickness, LSPR band position and excitation wavelength. The excitation of Ag NP LSPR, which overlaps the PpIX absorption band, leads to the concomitant enhancement of PpIX fluorescence and (1) O2 production independently of the Ag core size, but in a more pronounced way for larger Ag cores. These enhancements result from the increase of the PpIX excitation rate through the LSPR excitation and decrease when the distance between PpIX and Ag NPs increases. A maximum fluorescence enhancement of up to 14-fold, together with an increase of photogenerated (1) O2 production of up to 5 times are obtained using 100 nm Ag cores coated with a 5 nm thick silica coating. This article is protected by copyright. All rights reserved.

  14. Carbonic anhydrase IX-directed immunoliposomes for targeted drug delivery to human lung cancer cells in vitro.

    PubMed

    Wong, Blenda Chi Kwan; Zhang, Hongqi; Qin, Ling; Chen, Hubiao; Fang, Chen; Lu, Aiping; Yang, Zhijun

    2014-01-01

    Targeted drug delivery to cancer cells by use of antibody-conjugated liposomes (immunoliposomes) has attracted considerable interest in recent years. Despite increasing efforts in developing immunoliposomes as drug carriers, the investigation of useful tumor-associated antigen targets is far from complete. Carbonic anhydrase IX (CA IX) is a cell surface antigen characterized by hypoxia-induced expression in many solid tumors. This study investigated the feasibility of CA IX-directed immunoliposomes for targeted delivery of docetaxel to human lung cancer cells in vitro. Docetaxel-loaded immunoliposomes targeting CA IX were developed with an encapsulation efficiency of 84.4±3.9% and an average particle size of 143.9±11.1 nm. Using fluorescence-based flow cytometry, the in vitro binding activity of the immunoliposomes was found to be significantly higher (by 1.65-fold) than that of the nontargeted liposomes in CA IX-positive lung cancer cells, whereas no such difference was observed between the two groups when CA IX was not expressed. Furthermore, immunoliposomal docetaxel exhibited the strongest growth inhibitory effect against CA IX-positive lung cancer cells when compared with nontargeted liposomal docetaxel or free docetaxel solution. These data suggested that CA IX-directed immunoliposomes could serve as a promising drug delivery system for targeted killing of lung cancer cells.

  15. Functional Analysis of Adenovirus Protein IX Identifies Domains Involved in Capsid Stability, Transcriptional Activity, and Nuclear Reorganization

    PubMed Central

    Rosa-Calatrava, Manuel; Grave, Linda; Puvion-Dutilleul, Francine; Chatton, Bruno; Kedinger, Claude

    2001-01-01

    The product of adenovirus (Ad) type 5 gene IX (pIX) is known to actively participate in the stability of the viral icosahedron, acting as a capsid cement. We have previously demonstrated that pIX is also a transcriptional activator of several viral and cellular TATA-containing promoters, likely contributing to the transactivation of the Ad expression program. By extensive mutagenesis, we have now delineated the functional domains involved in each of the pIX properties: residues 22 to 26 of the highly conserved N-terminal domain are crucial for incorporation of the protein into the virion; specific residues of the C-terminal leucine repeat are responsible for pIX interactions with itself and possibly other proteins, a property that is critical for pIX transcriptional activity. We also show that pIX takes part in the virus-induced nuclear reorganization of late infected cells: the protein induces, most likely through self-assembly, the formation of specific nuclear structures which appear as dispersed nuclear globules by immunofluorescence staining and as clear amorphous spherical inclusions by electron microscopy. The integrity of the leucine repeat appears to be essential for the formation and nuclear retention of these inclusions. Together, our results demonstrate the multifunctional nature of pIX and provide new insights into Ad biology. PMID:11435594

  16. 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...

  17. Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

    PubMed Central

    Ahlskog, J K J; Schliemann, C; Mårlind, J; Qureshi, U; Ammar, A; Pedley, R B; Neri, D

    2009-01-01

    Background: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models. Methods: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology. Results: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies. Conclusion: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications. PMID:19623173

  18. 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...

  19. Achieving Gender Equity: A Basic Guide to Title IX and Gender Equity in Athletics for Colleges and Universities.

    ERIC Educational Resources Information Center

    National Collegiate Athletic Association, Overland Park, KS.

    This guide is designed to help college athletics administrators and faculty ensure that their program is in compliance with Title IX of the Education Amendments of 1972, which prohibits sex discrimination in educational programs, including college athletics, that receive or benefit from federal funding. It provides an overview of Title IX, the…

  20. 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

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Terms relating to other entities and concepts... 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...

  1. 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.

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

    ERIC Educational Resources Information Center

    Ramsey, Jeffrey T.

    2014-01-01

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

  3. 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 REGULATION FOR THE ADMINISTRATION AND ENFORCEMENT OF SECTIONS 799A AND 845 OF THE PUBLIC HEALTH SERVICE ACT Purposes; Definitions; Coverage §...

  4. 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.

  5. 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…

  6. Teachers May Sue for Retaliation when They Challenge Title IX Sex Discrimination Practices in Schools

    ERIC Educational Resources Information Center

    Essex, Nathan L.

    2005-01-01

    In a stunning 5-4 decision, the U.S. Supreme Court has held that teachers and coaches who suffer reprisals for raising complaints regarding illegal sex discrimination against their students can sue their school districts for damages. This ruling is unprecedented with respect to Title IX enforcement and will likely alter how school officials handle…

  7. The Promise of Title IX: Longitudinal Study of Gender in Urban School Administration, 1972 to 2002

    ERIC Educational Resources Information Center

    Mertz, Norma T.

    2006-01-01

    Using statistical data collected during a 30-year period, the article reports on the significant movement of females into all of the line administrative positions in the largest school districts in the country (by student population) since the passage of Title IX with one notable exception, that of superintendent. The position of superintendent…

  8. 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…

  9. Title IX Athletics Policies: Issues and Data for Education Decision Makers. Report.

    ERIC Educational Resources Information Center

    National Coalition for Women and Girls in Education.

    In 2002, the U.S. Department of Education established the Commission on Opportunity in Athletics to collect information, analyze issues, and obtain public input related to improving the application of current standards for measuring equal opportunity for boys and girls to participate in athletics under Title IX. The National Coalition of Woman and…

  10. More than Title IX: How Equity in Education Has Shaped the Nation

    ERIC Educational Resources Information Center

    Hanson, Katherine; Guilfoy, Vivian; Pillai, Sarita

    2009-01-01

    Women in America have come a long way in the last hundred years, from lacking the right to vote to holding some of the highest profile positions in the country. But this change has not come without struggle. "More Than Title IX" highlights the impact of one of the most powerful instruments of change--education. The book takes readers…

  11. 32 CFR 2003.9 - Reports to the President (Article IX).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... President of the United States. The Panel also includes such information in any reports it may make to the... 32 National Defense 6 2013-07-01 2013-07-01 false Reports to the President (Article IX). 2003.9... PANEL (ISCAP) BYLAWS, RULES, AND APPEAL PROCEDURES Bylaws § 2003.9 Reports to the President (Article...

  12. A Typology and Critique of Title IX Sexual Harassment Law after Gebser and Davis.

    ERIC Educational Resources Information Center

    Kaplin, William A.

    2000-01-01

    Addresses the recent history and current status of the sexual harassment problem in colleges and universities, focusing on the harassment of students by their teachers or peers and whether and how students can hold universities liable. Develops a typology of Title IX sexual harassment claims and their variable contexts, considers implications for…

  13. OATYC Journal, Vol. IX, Nos. 1-2, Autumn 1983-Spring 1984.

    ERIC Educational Resources Information Center

    Fullen, James, Ed.

    1984-01-01

    "OATYC Journal," which is published by the Ohio Association of Two-Year Colleges, is designed as a forum for the exchange of concepts, methods, and findings relevant to the two-year college classroom. Along with commentaries and letters of reaction from the readership, the two issues of volume IX present the following major articles: (1)…

  14. Beyond Title IX: PEER's State-by-State Guide to Women's Educational Equity Laws.

    ERIC Educational Resources Information Center

    Cusick, Theresa; And Others

    A guide to the status of state laws that prohibit sex discrimination in education is presented. The federal law (Title IX of the Education Amendments of 1972) is used as the standard against which state laws are measured. Based on a survey of the states (including the District of Columbia and the U.S. Territories) and an assessment of state…

  15. 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.

  16. 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.

  17. Multivalent pIX phage display selects for distinct and improved antibody properties

    PubMed Central

    Høydahl, Lene S.; Nilssen, Nicolay R.; Gunnarsen, Kristin S.; Pré, M. Fleur du; Iversen, Rasmus; Roos, Norbert; Chen, Xi; Michaelsen, Terje E.; Sollid, Ludvig M.; Sandlie, Inger; Løset, Geir Å.

    2016-01-01

    Phage display screening readily allows for the identification of a multitude of antibody specificities, but to identify optimal lead candidates remains a challenge. Here, we direct the antibody-capsid fusion away from the signal sequence-dependent secretory SEC pathway in E. coli by utilizing the intrinsic signal sequence-independent property of pIX to obtain virion integration. This approach was combined with the use of an engineered helper phage known to improve antibody pIX display and retrieval. By direct comparison with pIII display, we demonstrate that antibody display using this pIX system translates into substantially improved retrieval of desired specificities with favorable biophysical properties in de novo selection. We show that the effect was due to less E. coli host toxicity during phage propagation conferred by the lack of a signal sequence. This pIX combinatorial display platform provides a generic alternative route for obtaining good binders with high stability and may thus find broad applicability. PMID:27966617

  18. Title IX Self-Study Report of the Oklahoma City Public Schools.

    ERIC Educational Resources Information Center

    Lindley, Jesse B.

    Under Title IX of the Education Amendments of 1972, institutions affected must engage in appraisal and evaluation of current policies, practices, and procedures to determine possible discriminatory effects in five areas--athletics, counseling, curriculum and physical education, employment, and extracurricular activities. This report contains the…

  19. 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…

  20. African swine fever virus p72 genotype IX in domestic pigs, Congo, 2009.

    PubMed

    Gallardo, Carmina; Anchuelo, Raquel; Pelayo, Virginia; Poudevigne, Frédéric; Leon, Tati; Nzoussi, Jacques; Bishop, Richard; Pérez, Covadonga; Soler, Alejandro; Nieto, Raquel; Martín, Hilario; Arias, Marisa

    2011-08-01

    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.

  1. 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.

  2. Child Abuse and Neglect: A Resource Demonstration Program for Region IX. Final Report.

    ERIC Educational Resources Information Center

    Swinger, Hershel K.

    The Demonstration Resource Center was developed and funded for 3 years in Region IX of the United States (excluding Arizona) to establish a regional network for coordination and service delivery in child abuse and neglect. This final report states the purpose and lists the objectives of the center project, providing a brief overview of general…

  3. Flavobacterium columnare type IX secretion system mutations result in defects in gliding motility and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: 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 enzy...

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

    PubMed

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

    2010-01-03

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

  5. Teenage Pregnancy and Parenthood Issues under Title IX of the Education Amendments of 1972.

    ERIC Educational Resources Information Center

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

    This pamphlet has been prepared for elementary and secondary school administrators, teachers, counselors, parents, and students. It describes school retention problems associated with teenage pregnancy and parenthood and the requirements pertaining to these issues contained in the U.S. Department of Education regulation implementing Title IX.…

  6. Decision Making in Intercollegiate Athletics: One Institution's Journey to Maintain Title IX Compliance

    ERIC Educational Resources Information Center

    Rowland, John W.

    2012-01-01

    The allocation of resources and participation opportunities in intercollegiate athletics has been a debate among researchers for nearly 40 years. Title IX and traditionally male-dominated budgeting practices continue to be opposing forces that shape the financial and gender makeup of university athletic departments. In fact, the need to be Title…

  7. 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 ...

  8. Effectiveness of CAI Package on Achievement in Physics of IX Standard Students

    ERIC Educational Resources Information Center

    Maheswari, I. Uma; Ramakrishnan, N.

    2015-01-01

    The present study is an experimental one in nature, to find out the effectiveness of CAI package on in Physics of IX std. students. For this purpose a CAI package was developed and validated. The validated CAI package formed an independent variable of this study. The dependent variable is students' achievements in physics content. In order to find…

  9. Multivalent pIX phage display selects for distinct and improved antibody properties.

    PubMed

    Høydahl, Lene S; Nilssen, Nicolay R; Gunnarsen, Kristin S; Pré, M Fleur du; Iversen, Rasmus; Roos, Norbert; Chen, Xi; Michaelsen, Terje E; Sollid, Ludvig M; Sandlie, Inger; Løset, Geir Å

    2016-12-14

    Phage display screening readily allows for the identification of a multitude of antibody specificities, but to identify optimal lead candidates remains a challenge. Here, we direct the antibody-capsid fusion away from the signal sequence-dependent secretory SEC pathway in E. coli by utilizing the intrinsic signal sequence-independent property of pIX to obtain virion integration. This approach was combined with the use of an engineered helper phage known to improve antibody pIX display and retrieval. By direct comparison with pIII display, we demonstrate that antibody display using this pIX system translates into substantially improved retrieval of desired specificities with favorable biophysical properties in de novo selection. We show that the effect was due to less E. coli host toxicity during phage propagation conferred by the lack of a signal sequence. This pIX combinatorial display platform provides a generic alternative route for obtaining good binders with high stability and may thus find broad applicability.

  10. Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms IX and XII.

    PubMed

    Ibrahim, Hany S; Abou-Seri, Sahar M; Tanc, Muhammet; Elaasser, Mahmoud M; Abdel-Aziz, Hatem A; Supuran, Claudiu T

    2015-10-20

    New series of benzenesulfonamide derivatives incorporating pyrazole and isatin moieties were prepared using celecoxib as lead molecule. Biological evaluation of the target compounds was performed against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more precisely against the human isoforms hCA I, II (cytosolic), IX and XII (transmembrane, tumor-associated enzymes). Most of the tested compounds efficiently inhibited hCA I, II and IX, with KIs of 2.5-102 nM, being more effective than the reference drug acetazolamide. Compounds 11e, 11f, 16e and 16f were found to inhibit hCA XII with Ki of 3.7, 6.5, 5.4 and 7.2 nM, respectively. Compounds 11e and 16e, with 5-NO2 substitution on the isatin ring, were found to be selective inhibitors of hCA IX and hCA XII. Docking studies revealed that the NO2 group of both compounds participate in interactions with Asp132 within the hCA IX active site, and with residues Lys67 and Asp130 in hCA XII, respectively.

  11. Effect of PpIX photoproducts formation on pO2 measurement by time-resolved delayed fluorescence spectroscopy of PpIX in solution and in vivo.

    PubMed

    Huntosova, Veronika; Gerelli, Emmanuel; Zellweger, Matthieu; Wagnières, Georges

    2016-11-01

    The measurement of Protoporphyrin IX delayed fluorescence lifetime is a minimally invasive method for monitoring the levels of oxygen in cells and tissues. The excitation of Protoporphyrin IX during this measurement can lead to the formation of photoproducts in vitro and in vivo. The influence of their luminescence on the measured Protoporphyrin IX delayed fluorescence lifetimes was studied in solution and in vivo on the Chick's chorioallantoic membrane (CAM) model under various oxygen enriched air conditions (0mmHg, 37mmHg and 155mmHg). The presence of photoproducts disturbs such measurements since the delayed fluorescence emission of some of them spectrally overlaps with that of Protoporphyrin IX. One possible way to avoid this obstacle is to detect Protoporphyrin IX's delayed fluorescence lifetime in a very specific spectral range (620-640nm). Another possibility is to excite Protoporphyrin IX with light doses much lower than 10J/cm(2), quite possibly as low as a fraction 1J/cm(2) at 405nm. This leads to an increased accuracy of pO2 detection. Furthermore, this method allows combination of diagnosis and therapy in one step. This helps to improve detection systems and real-time identification of tissue respiration, which is tuned for the detection of PpIX luminescence and not its photoproducts.

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

    PubMed

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

    2016-01-01

    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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX.

    PubMed

    Alterio, Vincenzo; Hilvo, Mika; Di Fiore, Anna; Supuran, Claudiu T; Pan, Peiwen; Parkkila, Seppo; Scaloni, Andrea; Pastorek, Jaromir; Pastorekova, Silvia; Pedone, Carlo; Scozzafava, Andrea; Monti, Simona Maria; De Simone, Giuseppina

    2009-09-22

    Carbonic anhydrase (CA) IX is a plasma membrane-associated member of the alpha-CA enzyme family, which is involved in solid tumor acidification. It is a marker of tumor hypoxia and a prognostic factor in several human cancers. An aberrant increase in CA IX expression in chronic hypoxia and during development of various carcinomas contributes to tumorigenesis through at least two mechanisms: pH regulation and cell adhesion control. Here we report the X-ray structure of the catalytic domain of CA IX in complex with a classical, clinically used sulfonamide inhibitor, acetazolamide. The structure reveals a typical alpha-CA fold, which significantly differs from the other CA isozymes when the protein quaternary structure is considered. Thus, two catalytic domains of CA IX associate to form a dimer, which is stabilized by the formation of an intermolecular disulfide bond. The active site clefts and the PG domains are located on one face of the dimer, while the C-termini are located on the opposite face to facilitate protein anchoring to the cell membrane. A correlation between the three-dimensional structure and the physiological role of the enzyme is here suggested, based on the measurement of the pH profile of the catalytic activity for the physiological reaction, CO(2) hydration to bicarbonate and protons. On the basis of the structural differences observed between CA IX and the other membrane-associated alpha-CAs, further prospects for the rational drug design of isozyme-specific CA inhibitors are proposed, given that inhibition of this enzyme shows antitumor activity both in vitro and in vivo.

  18. Influence of formulation factors on methyl-ALA-induced protoporphyrin IX accumulation in vivo.

    PubMed

    Donnelly, Ryan F; Juzenas, Petras; McCarron, Paul A; Ma, Li-Wei; Woolfson, A David; Moan, Johan

    2006-09-01

    Photodynamic therapy (PDT) is a medical treatment by which a combination of a photosensitising drug and visible light cause the destruction of selected cells. Thick lesions, such as nodular basal cell carcinomas (BCCs), or lesions with overlying keratinous debris, are reported as being difficult to eradicate using 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). Such treatment failures have been attributed to the shallow penetration of water-soluble drugs like ALA. In addition, the current scarcity of sophisticated drug delivery research centered on PDT applications has meant that accurate comparison of similar clinical studies is difficult. This paper investigates, for the first time, novel drug delivery systems for controlled drug delivery of methyl-ALA (M-ALA). Pressure sensitive adhesive (PSA) and bioadhesive patches containing defined M-ALA loadings and a standard cream containing equivalent amounts of drug were applied to the skin of mice for defined periods of time and the fluorescence of the protoporphyrin IX (PpIX) induced measured over 24h. Of major importance, the PSA patches containing low drug loadings induced high PpIX levels, which were limited to the site of application, after only 1h applications. Such systems have the potential to improve selectivity of PpIX accumulation, increase simplicity of treatment and, due to the low drug loadings required, reduce costs of clinical PDT. PSA patches would be most suitable for application to areas of dry skin, while bioadhesive patches would be suitable for moist areas, such as the mouth or lower female reproductive tract and have been shown here to induce significant PpIX production at the site of application after 4h applications of patches containing high drug loadings.

  19. 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.

  20. 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.

  1. Formation and accumulation of protoporphyrin IX in tumor and nontumor cell lines induced by 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Fernandez, Sandra R.; Milanetto, Marilia; Bagnato, Vanderlei S.; Imasato, Hidetake; Perussi, Janice R.

    2005-04-01

    The endogenous photosensitizer 5-aminolevulinic acid (ALA) is a haem precursor and induces the synthesis of protoporphyrin IX (PpIX) in mitochondria-containing cells. Due to the slow conversion of porphyrins to haem, high levels of PPIX are found in the tissues, sufficient to produce a photodynamic effect following exposure to light. Since PpIX accumulates effectively in tumor cells, the use of ALA leads to a better photoselectivity than Photofrin. However, this selectivity has not been sufficiently studied. As far as we know there is just one study comparing the amount of accumulated PpIX in non-tumor and tumor cell lines. In this work we attempt to compare not just the production but also the accumulation and cytotoxicity of PpIX in non-tumor (VERO) versus tumor (Hep-2) cells induced by the use of ALA. The results have shown that both non-tumor and tumor cell lines produce the same amount of PpIX but just the tumor cells can accumulate PpIX. So, under illumination, only the tumor cells will be killed.

  2. 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.

  3. 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.

  4. Intersex (ix) mutations of Drosophila melanogaster cause nonrandom cell death in genital disc and can induce tumours in genitals in response to decapentaplegic (dpp(disk)) mutations.

    PubMed

    Chatterjee, R N; Chatterjee, P; Kuthe, S; Acharyya-Ari, M; Chatterjee, R

    2015-06-01

    In Drosophila melanogaster, the intersex (ix) is a terminally positioned gene in somatic sex determination hierarchy and function with the female specific product of double sex (DSX(F)) to implement female sexual differentiation. The null phenotype of ix is to transform diplo-X individuals into intersexes while leaving haplo-X animals unaffected. This study on the effect of different intersex mutations on genital disc development provides the following major results: (i) similar range of a characteristic array of morphological structures (from almost double sex terminalia to extreme reduction of terminal appendages) was displayed by the terminalia of XX ix(1)/ix(1) , XX ix(2)/ix(2) and XX ix(5)/ix(5) individuals; (ii) an increased number of apoptotic cells were found to occur in a localized manner in mature third instar larval genital discs of ix individuals; (iii) ix mutations can induce high frequency of neoplastic tumours in genitals in the presence of decapentaplegic (dpp(disk)) mutations; and (iv) heteroallelic combinations of dpp(disk) mutations can also induce tumours in intersex genitals with variable expressivity. On the basis of these findings, we suggest that: (i) loss of function of ix causes massive cell death in both male and female genital primordia of genital discs, resulting phenotype mimicking in male and female characteristics in genitals; and (ii) at the discs, the apoptotic cells persist as 'undead' cells that can induce oncogenic transformation in the neighbouring disc cells when dpp signalling is blocked or reduced by dpp(disk) mutations.

  5. Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging

    PubMed Central

    Sunar, Ulas; Rohrbach, Daniel J.; Morgan, Janet; Zeitouni, Natalie; Henderson, Barbara W.

    2013-01-01

    5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is an attractive treatment option for nonmelanoma skin tumors, especially for multiple lesions and large areas. The efficacy of ALA-PDT is highly dependent on the photosensitizer (PS) concentration present in the tumor. Thus it is desirable to quantify PS concentration and distribution, preferably noninvasively to determine potential outcome. Here we quantified protoporphyrin IX (PpIX) distribution induced by topical and intra-tumoral (it) administration of the prodrug ALA in basal and squamous cell carcinoma murine models by using spatial frequency domain imaging (SFDI). The in vivo measurements were validated by analysis of the ex vivo extraction of PpIX. The study demonstrates the feasibility of non-invasive quantification of PpIX distributions in skin tumors. PMID:23577288

  6. Effects of Title IX and sports participation on girls' physical activity and weight.

    PubMed

    Kaestner, Robert; Xu, Xin

    2007-01-01

    In this study, we examined the association between girls' participation in high school sports and the physical activity, weight, body mass, and body composition of adolescent females during the 1970s when girls' sports participation was dramatically increasing as a result of Title IX. We found that increases in girls' participation in high school sports, a proxy for expanded athletic opportunities for adolescent females, were associated with an increase in physical activity and an improvement in weight and body mass among girls. In contrast, adolescent boys experienced a decline in physical activity and an increase in weight and body mass during the period when girls' athletic opportunities were expanding. Taken together, these results strongly suggest that Title IX and the increase in athletic opportunities among adolescent females it engendered had a beneficial effect on the health of adolescent girls.

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

    PubMed

    Kaestner, Robert; Xin Xu

    2010-02-01

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

  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. 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

  10. 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

  11. 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.

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

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  13. 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.

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

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2014-01-08

    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.

  17. Relation of factor VIII and IX inhibitors with ABO blood groups in 150 patients with haemophilia A and B.

    PubMed

    Torghabeh, Hassan Mansouri; Pourfathollah, Aliakbar; Shooshtari, Mahmood Mahmoodian; Yazdi, Zahra Rezaie

    2006-03-01

    Many investigations have proved relations between ABO blood groups with some diseases and factor VIII and von willebrand level in plasma. In this study we investigated a relation between ABO blood groups and factor VIII and IX inhibitors in 102 patients with haemophilia A and 48 patients with haemophilia B. The assay of inhibitor was done by Bethesda method. There were no relation between ABO blood groups and factor VIII and IX inhibitors.

  18. 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.

  19. 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.

  20. FUNDAMENTALS OF AMHARIC (REVISED EDITION), UNITS VIII-IX. DIALOGUES FOR CONVERSATION, AMHARIC SCRIPT.

    ERIC Educational Resources Information Center

    BARTON, DONALD K.; AND OTHERS

    THIS IS THE THIRD AND FINAL VOLUME OF A NINE-UNIT COURSE IN BASIC AMHARIC. VOLUMES ONE AND TWO DEAL WITH THE PROBLEMS OF PRONUNCIATION AND THE ORAL-AURAL MASTERY OF BASIC GRAMMATICAL CONSTRUCTIONS. AT THE END OF EACH VOLUME ARE APPENDED ENGLISH-AMHARIC AND AMHARIC-ENGLISH GLOSSARIES. VOLUME THREE (UNITS VIII-IX) IS DIVIDED INTO TWO PARTS. PART I…

  1. A Spectroelectrochemical Investigation Oxidation of the Bilirubin IX-Alpa in Dimethylformamide.

    DTIC Science & Technology

    1984-11-28

    purification of the IX-a natural isomer. The commercial material, generally isolated from oxen bile or gallstones , was dissolved in chloroform by boilinq... cause the wave to appear.’ 1/2 The decrease in slope of the i - plots and an anodic shift for the p +0.10 V wave with increased acid strength of the...center pyrrole nitrogen (Figure 18). In the neutral species, the two carboxylic acid groups are hydrogen bonded to these pyrrole nitrogens causing

  2. Factor IX Amagasaki: A new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities

    SciTech Connect

    Miyata, Toshiyuki; Iwanaga, Sadaaki ); Sakai, Toshiyuki; Sugimoto, Mitsuhiko; Naka, Hiroyuki; Yamamoto, Kazukuni; Yoshioka, Akira; Fukui, Hiromu ); Mitsui, Kotoko; Kamiya, Kensyu; Umeyama, Hideaki )

    1991-11-26

    Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. The authors identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate for factor X in the presence of factor VIII, phospholipids, and Ca{sup 2+}, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311 {yields} Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

  3. 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.

  4. 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.

  5. Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

    PubMed Central

    Nakayama, Taku; Otsuka, Shimpei; Kobayashi, Tatsuya; Okajima, Hodaka; Matsumoto, Kentaro; Hagiya, Yuichiro; Inoue, Keiji; Shuin, Taro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2016-01-01

    Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor. PMID:27857072

  6. Early neoplastic and metastatic mammary tumours of transgenic mice detected by 5-aminolevulinic acid-stimulated protoporphyrin IX accumulation

    PubMed Central

    Dorward, A M; Fancher, K S; Duffy, T M; Beamer, W G; Walt, H

    2005-01-01

    A photodynamic technique for human breast cancer detection founded upon the ability of tumour cells to rapidly accumulate the fluorescent product protoporphyrin IX (PpIX) has been applied to transgenic mouse models of mammary tumorigenesis. A major goal of this investigation was to determine whether mouse mammary tumours are reliable models of human disease in terms of PpIX accumulation, for future mechanistic and therapeutic studies. The haeme substrate 5-aminolevulinic acid (5-ALA) (200 mg kg−1) was administered to mouse strains that develop mammary tumours of various histological subtypes upon expression of the transgenic oncogenes HRAS, Polyoma Virus middle T antigen, or Simian Virus 40 large T antigen in the mammary gland. Early neoplastic lesions, primary tumours and metastases showed consistent and rapid PpIX accumulation compared to the normal surrounding tissues, as evidenced by red fluorescence (635 nm) when the tumours were directly illuminated with blue light (380–440 nm). Detection of mouse mammary tumours at the stage of ductal carcinoma in situ by red fluorescence emissions suggests that enhanced PpIX synthesis is a good marker for early tumorigenic processes in the mammary gland. We propose the mouse models provide an ideal experimental system for further investigation of the early diagnostic and therapeutic potential of 5-ALA-stimulated PpIX accumulation in human breast cancer patients. PMID:16251872

  7. 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

  8. 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.

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

    DOE PAGES

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

    2015-09-23

    Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO2to 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, whereasmore » 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, anRcryst of 18.0% and anRfree of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

    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 R cryst of 18.0% and an R free 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

  12. Induction by hypoxia combined with low glucose or low bicarbonate and high posttranslational stability upon reoxygenation contribute to carbonic anhydrase IX expression in cancer cells.

    PubMed

    Rafajová, Monika; Zatovicová, Miriam; Kettmann, Richard; Pastorek, Jaromír; Pastoreková, Silvia

    2004-04-01

    Hypoxia is an important factor of tumor microenvironment that significantly influences behaviour of tumor cells via activation of genes whose products are involved in adaptation to hypoxic stress, such as vascular endothelial growth factor (VEGF) and glucose transporter (GLUT-1). Carbonic anhydrase IX (CA IX) is one of the most strongly hypoxia-inducible proteins with potential value as an intrinsic marker of hypoxia. However, intratumoral distribution of CA IX only partially overlaps with distribution of VEGF and GLUT-1 indicating that regulation of CA IX differs from the regulation of other hypoxic markers. Therefore, we analysed CA IX expression in response to hypoxia combined with other stresses, and determined the stability of CA IX protein upon reoxygenation using HeLa cells as a model. We found that both hypoxia-induced transcription and CA IX protein level are further increased by reduced glucose or bicarbonate concentrations. Post-translational stability of CA IX was assessed by monitoring the quantity of biotinylated protein extracted at different time points from the cells labelled immediately after shift to reoxygenation. CA IX protein half-life in reoxygenated cells was 38 h and was independent of the duration of the foregoing hypoxia. This finding has potential implications for interpretation of clinical data as it suggests that CA IX expression may detect not only actually hypoxic tumor regions, but also the regions affected by hypoxia and adverse microenvironmental stresses before biopsy or tumor removal.

  13. Anaerobic-ion exchange (AN-IX) process for local-scale nitrogen recovery from wastewater.

    PubMed

    Smith, Daniel P; Smith, Nathaniel T

    2015-11-01

    An anaerobic-ion exchange (AN-IX) process was developed for point-of-origin recovery of nitrogen from household wastewater. The process features upflow solids-blanket anaerobic treatment (ammonification) followed by ammonium ion exchange onto natural zeolite. The AN-IX system is configured as a series of linked upflow chambers that operate passively without energy input, and is amenable to intermittent and seasonal operation. A 57L prototype was operated for over 1.8 years treating actual wastewater under field conditions. Total nitrogen removal exceeded 96% through the first 160 days of operation and effluent ammonium nitrogen remained below detection for 300 days. Ion exchange chambers exhibited sequential NH4(+)-N breakthrough over extended operation and complete media exhaustion was approached at Day 355. The ammonium capacity of zeolite was estimated as 13.5mg NH4(+)-N per gram dry weight. AN-IX is a resilient and cost effective process for local-scale nitrogen recovery and reuse, suitable for small scale and larger systems.

  14. 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.

  15. 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.

  16. The comparative radiopacity of Fuji IX-GP, an intermediate restorative material.

    PubMed

    DuBois, D J; Reichl, R B; Hondrum, S O

    2000-04-01

    The radiopacity of intermediate restorative materials should be sufficient to enable the clinician to distinguish the material from normal and decalcified tooth structure. The purpose of this study was to determine the relative radiopacities of intermediate restorative materials, including a newly introduced high-viscosity, self-cured, condensable glass ionomer material. Radiographs were made of six intermediate restorative materials: two reinforced zinc oxide-eugenol materials (IRM and Zinroc), a conventional glass ionomer material (Ketac-fil), a synthetic resin material (Cavit), a eugenol-free zinc oxide material (Tempit), and a new, general-purpose, condensable glass ionomer material (Fuji IX-GP). Optical density was measured using a densitometer. The optical density of dentin and enamel were used for radiographic comparison. Statistical analysis revealed significant differences among materials: Cavit = IRM = Tempit > Zinroc = Fuji IX-GP > Ketac-fil = enamel > dentin (where > indicates a statistical difference at p < or = 0.05). Although not as radiopaque as some other intermediate materials tested, the radiopacity of Fuji IX-GP appears sufficient to aid diagnosis.

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  18. [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.

  19. Systemic component of protoporphyrin IX production in nude mouse skin upon topical application of aminolevulinic acid depends on the application conditions.

    PubMed

    van den Akker, Johanna T H M; Iani, Vladimir; Star, Willem M; Sterenborg, Henricus J C M; Moan, Johan

    2002-02-01

    Topical application of 5-aminolevulinic acid (ALA) for protoporphyrin IX (PpIX)-based photodynamic therapy of skin cancer is generally considered not to induce systemic side effects because PpIX is supposed to be formed locally. However, earlier studies with topically applied ALA have revealed that in mice PpIX is not only produced in the application area but also in other organs including skin outside the application area, whereas esterified ALA does not. From these results, it was concluded that it is not redistribution of circulating PpIX that causes the fluorescence distant from the ALA application site, but rather, local PpIX production induced by circulating ALA. In the present study we investigate the effects of the ALA concentration in the cream, the application time, the presence of a penetration enhancer, the presence of the stratum corneum and esterification of ALA on the PpIX production in nude mouse skin outside the area where ALA is applied. For this purpose, ALA and ALA hexyl ester (ALAHE) were applied to one flank, and the PpIX fluorescence was measured in the contralateral flank. During a 24 h application of ALA, PpIX was produced in the contralateral flank. No PpIX could be detected in the contralateral flank after ALA application times ranging from 1 to 60 min. Tape-stripping the skin prior to short-term ALA application, but not the addition of a penetration enhancer, resulted in PpIX production in the contralateral flank. When ALAHE was applied, no PpIX fluorescence was measured in the contralateral flank under any application condition. The results suggest that the systemic component of PpIX production outside the ALA application area plays a minor or no role in relevant clinical situations, when the duration of ALA (ester) application is relatively short and a penetration enhancer is possibly added.

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

    PubMed Central

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

    2011-01-01

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

  1. Inactivation and clearance of viruses during the manufacture of high purity factor IX.

    PubMed

    Johnston, A; Macgregor, A; Borovec, S; Hattarki, M; Stuckly, K; Anderson, D; Goss, N H; Oates, A; Uren, E

    2000-09-01

    Haemophilia is a bleeding disorder characterised by a deficiency in Factor IX. Replacement therapy in the form of a Factor IX concentrate is a widely accepted practice. In this paper we describe a double virus inactivated chromatographic process for producing a high purity Factor IX product, MonoFIX((R))-VF. The process involves separation of the prothrombin complex by cryoprecipitation, fraction I precipitation and DEAE-cellulose adsorption, further ion-exchange chromatography of crude Factor IX, followed by solvent/detergent treatment. Heparin affinity chromatography is then used to further purify Factor IX. Final nanofiltration is sequential through 35 nm then 15 nm membrane filters. The principal virus inactivation/removal steps are solvent/detergent treatment and nanofiltration and the partitioning of relevant and model viruses provides further reduction in virus load through the production process.Solvent/detergent treatment was shown to achieve log reduction factors of 4.5 for HIV-1, 5.1 for Sindbis virus, 6.1 for vesicular stomatitis virus (VSV), 5.1 for bovine viral diarrhoea virus (BVDV) and 5.3 for pseudorabies virus (PRV). BVDV is a model for hepatitis C virus (HCV), and pseudorabies virus (PRV), like hepatitis B virus (HBV) is an enveloped DNA virus. Using scaled down models of the production process, we have also demonstrated the neutralization/partitioning of at least 6 logs of hepatitis A virus (HAV) during cryoprecipitation, Fraction I precipitation, and the DEAE adsorption and elution step, and a further 1.6 log reduction in HAV load as a result of heparin affinity chromatography. The log reduction factors for HAV as a result of the second ion-exchange chromatography step and as a result of enhanced neutralisation associated with solvent/detergent treatment were not significant. Nanofiltration was shown to contribute a further log reduction factor of 6.7 for HAV and 5.8 for BVDV indicating that log reduction factors of this order would be obtained

  2. Carbonic anhydrase IX (CA-IX) and human papillomavirus (HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study

    PubMed Central

    Liao, Shu-Yuan; Rodgers, William H.; Kauderer, James; Bonfiglio, Thomas A.; Walker, Joan L.; Darcy, Kathleen M.; Carter, Randy; Hatae, Masayuji; Levine, Lyuba; Spirtos, Nick M; Stanbridge, Eric J.

    2009-01-01

    High-risk human papillomavirus (H-HPV) infection is strongly linked to cervical neoplasia but its role in detecting glandular lesions is unclear. In the cervix, carbonic anhydrase IX (CA-IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H-HPV was detected using Hybrid Capture 2 (HC2) in liquid based cytology and CA-IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA-IX testing alone (n=403) had a sensitivity of 75%, 95%, or 65% for SCLs, significant glandular lesions (GLs) or squamous lesions (SLs), respectively, with a specificity of 88%, and a false negative rate (FNR defined as one minus negative predictive value) of 10%. Testing for H-HPV (n=122) had a sensitivity of 97%, 100%, or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87%, and a FNRof 1%. The combination of CA-IX and H-HPV testing (n=122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H-HPV testing alone. The conclusions of this study are that both H-HPV and CA-IX testing are useful diagnostic markers for GLs. However, H-HPV testing is a better diagnostic marker for SLs. The combination of CA-IX with H-HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H-HPV testing alone. PMID:19670419

  3. 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.

  4. Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy

    PubMed Central

    Kanick, SC; Davis, SC; Zhao, Y; Sheehan, KL; Hasan, T; Maytin, EV; Pogue, BW; Chapman, MS

    2015-01-01

    Background Although Aminolevulinic Acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT. Methods A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48–76 hours after treatment (n=13). Results PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥ 5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p<0.022) (n=70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n=13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r=0.17, p<0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r=0.55, p < 0.051) and erythema (r=0.58, p < 0.039) in the 48–72 hr following treatment. Conclusions These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes. PMID:26480810

  5. Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment.

    PubMed

    Martin, A; Tope, W D; Grevelink, J M; Starr, J C; Fewkes, J L; Flotte, T J; Deutsch, T F; Anderson, R R

    1995-01-01

    Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice

    PubMed Central

    Verma, Dheeraj; Moghimi, Babak; LoDuca, Paul A.; Singh, Harminder D.; Hoffman, Brad E.; Herzog, Roland W.; Daniell, Henry

    2010-01-01

    To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin β-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20–25% of control animals survived after six to eight F.IX doses, 90–93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2–5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5–80 μg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (∼40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment. PMID:20351275

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

    PubMed

    Corbell, M J

    1975-08-01

    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.

  8. Differential co-expression of long and short form type IX collagen transcripts during avian limb chondrogenesis in ovo.

    PubMed

    Swiderski, R E; Solursh, M

    1992-05-01

    Using RNA blot analysis of developmentally staged avian limb buds, we demonstrate that transcripts of several cartilage marker genes appear in limb tissue prior to overt chondrogenesis. Type II collagen mRNA, cartilage proteoglycan core protein mRNA, alpha 2(IX) collagen mRNA, and transcripts of the short form alpha 1(IX) collagen chain derived from the downstream promoter are co-expressed in limb tissue approximately 24-36 hours before the appearance of the respective polypeptides in differentiating cartilagenous tissue. Transcripts of the long form alpha 1(IX) collagen chain derived from the upstream promoter appear somewhat later in development; nearly coincident with the immunolocalization of type IX collagen in the cartilage elements of the limb. The spatial distribution of type II and type IX collagen transcripts was analyzed by in situ hybridization. Type II collagen and the long form alpha 1(IX) collagen transcripts co-localized in the chondrogenic elements of the developing forelimb. In contrast, short form alpha 1(IX) collagen transcripts which lack the 5' region encoding the NC4 globular amino-terminal domain were distributed throughout the non-chondrogenic, non-myogenic mesenchymal regions of the limb and were not detectable above background levels in the limb chondrogenic elements. The precocious appearance of several cartilage marker gene transcripts prior to chondrogenesis suggests that multiple levels of gene regulation including alternative promoter use, alternative RNA splicing, alternative polyadenylation, and other post-transcriptional as well as translational mechanisms are active prior to, and during avian limb chondrogenesis.

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  10. 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.

  11. Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma

    PubMed Central

    Lv, Yanhong; Zheng, Jinhua; Zhou, Qi; Jia, Limin; Wang, Chunying; Liu, Nian; Zhao, Hong; Ji, Hang; Li, Baoxin; Cao, Wenwu

    2017-01-01

    Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3–4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53. PMID:28102324

  12. 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

  13. [Construction of nonsense-mutated eukaryotic expression vector of factor IX gene and its expression in COS-7 cells].

    PubMed

    Nie, Xin; Yang, Lin-Hua; Chai, Bao-Feng; Shen, Quan; Zhang, Yuan; Zhang, Yao-Fang; Chen, Jian-Fang

    2010-06-01

    The purpose of this study was to construct 4 types of nonsense-mutated eukaryotic expression plasmids of fIX gene, using pcDNA3.1 plasmid containing fIX cDNA as template, and to identify, then to perform their expression in COS-7 cells. These stop mutants constructed by site-directed mutagenesis based on PCR, and further confirmed by DNA sequencing. COS-7 cells were transfected with either the wild-type or mutated fIX expression constructs, then the relative expression levels of fIX mRNA were detected by real time fluorescent quantitative PCR. The result showed that except the designed sites, there were no other nucleotide mutation in the sequences of four nonsense mutants. The results of real time PCR proved that the nonsense-mutated vectors can be effectively expressed in COS-7 cells. It is concluded that the nonsense-mutated eukaryotic expression vectors of fIX gene have been successfully constructed and can express in COS-7 cells, which provides the material basis for further researches on mechanism and treatment of FIX deficiency and the function defects caused by nonsense mutation.

  14. 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.

  15. New reconstruction and morphological description of a Homo erectus cranium: skull IX (Tjg-1993.05) from Sangiran, Central Java.

    PubMed

    Kaifu, Yousuke; Zaim, Yahdi; Baba, Hisao; Kurniawan, Iwan; Kubo, Daisuke; Rizal, Yan; Arif, Johan; Aziz, Fachroel

    2011-09-01

    Skull IX (Tjg-1993.05) was unearthed from the upper stratigraphic zone (Bapang-AG levels) of the hominin-bearing sequence in Sangiran. This remarkably complete cranial specimen of Homo erectus from the early Pleistocene of Java preserves substantial portions of the vault and face. However, the distortion present in the original reconstruction has hampered detailed documentation of its morphological characteristics. We here report a new reconstruction of Skull IX that successfully recovers the original morphology and significantly differs from previous reconstructions. Detailed morphological description and the results of initial comparative analyses based on this new reconstruction are provided. The endocranial volume of Skull IX was measured as 870 cc using micro-CT data. The neurocranium of Skull IX is slightly smaller than the so far recorded smallest cranium from this zone, suggesting this individual was female. In most, but not all, aspects of the cranial vault form, details of the external surface structures, and facial morphology, Skull IX exhibits numerous similarities to the other Bapang-AG H. erectus specimens, indicating that it belonged to the Bapang-AG H. erectus population. Drawing on the expanded fossil sample of this chronoregional H. erectus group, we discuss their evolutionary status, degree of sexual dimorphism, and facial morphological variation in Afro-Asian earlier Homo specimens.

  16. 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.

  17. The rates and patterns of deletions in the human factor IX gene

    SciTech Connect

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. )

    1994-02-01

    Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. The prevalence of factor VIII and IX inhibitors among Saudi patients with hemophilia

    PubMed Central

    Owaidah, Tarek; Momen, Abdulkareem Al; Alzahrani, Hazzaa; Almusa, Abdulrahman; Alkasim, Fawaz; Tarawah, Ahmed; Nouno, Randa Al; Batniji, Fatima Al; Alothman, Fahad; Alomari, Ali; Abu-Herbish, Saud; Abu-Riash, Mahmoud; Siddiqui, Khawar; Ahmed, Mansor; Mohamed, SY; Saleh, Mahasen

    2017-01-01

    Abstract Hemophilia A and B are X-linked diseases that predominantly affect male patients. Patients can develop coagulation factor inhibitors, which exponentially increases the treatment cost. However, the prevalence of factor VIII and IX inhibitors in Saudi Arabia is unclear. This study aimed to determine the Saudi prevalence of factor VIII and IX inhibitors. This 4-year, 7-center, cross-sectional study evaluated the Saudi prevalences of hemophilia A and B. We collected the patients’ clinical data, evaluated their disease, and tested for factor inhibitors. We included 202 patients with hemophilia (median age at diagnosis: 0.13 years, range: birth–34.8 years). The patients included 198 male patients (98%), 148 patients with hemophilia A (73.3%), and 54 patients with hemophilia B (26.7%). The patients exhibited severe factor VIII activity (<1%; 121 patients; 5.2%), moderate activity (1–5%; 7 patients; 4.9%), and mild activity (14 patients; 9.9%). Among the patients with care-related data, most patients were treated for episodic bleeding (76.8%) or received prophylaxis (22.6%); 1 patient received both treatments. Among the patients with source-related data, the factor replacements were derived from plasma (48.4%), recombinant concentrates (22.9%), both sources (14.6%), or fresh frozen plasma (14.1%). Factor VIII inhibitors were observed in 43 (29.3%) of the 147 patients, and only 1 of the 54 patients developed factor IX inhibitors. Most patients who developed inhibitors had severe hemophilia (40/44; 90.9%), and inhibitors were also common among patients who received recombinant products (14/43; 32.6%). The Saudi prevalence of factor inhibitors was similar to those among other ethnic populations. PMID:28079788

  3. Derivation of Aero-Induced Fluctuating Pressure Environments for Ares I-X

    NASA Technical Reports Server (NTRS)

    Yang, Michael Y.; Wilby, John F.

    2008-01-01

    A description is given of the external aero-inducted fluctuating pressure model which was fit and anchored to wind tunnel data from the past 40 years. This model is based upon the assumption that the flow around a vehicle can be divided into discrete flow zones with independent fluctuating pressure properties. The model is then used to derive fluctuating pressure environments during ascent for the Ares I-X test vehicle. A sensitivity study of the structural response to the spatial correlation of the fluctuating pressures is also performed.

  4. The Ripple Effect of Title IX on Women's Health Issues: Treating an Increasingly Active Population.

    PubMed

    Mees, Patricia D

    2003-04-01

    Perhaps no area in sports medicine has changed as dramatically in the last 30 years as women's health. Title IX of the Education Amendments of 1972 prohibited discrimination on the basis of sex in all curricular and extracurricular activities at educational institutions that receive federal funding. Before 1972, many assumed that women were not interested in sports and that there was no need to provide programs for girls and women, and most primary care physicians had little experience in treating female athletes and other active women.

  5. Modern history of women in sports. Twenty-five years of Title IX.

    PubMed

    Lopiano, D A

    2000-04-01

    The impact of federal anti-discrimination laws such as Title IX and the Amateur Sports Act have opened the doors of sport participation opportunity to girls and women in sports over the last 25 years. Such participation has created new and more lucrative consumer markets for sporting goods manufactures, as well as college and professional sports teams. The prospect of economic gain has created significant social changes: Women are now being encouraged to participate in sports and embrace the resulting benefits, and the general public is showing increased support for gender equity in sports.

  6. The 3d84s-3d84p transitions in Br IX

    NASA Astrophysics Data System (ADS)

    Zeng, X. T.; Jupén, C.; Livingston, A. E.; Westerlind, M.; Engström, L.; Martinson, I.

    1990-08-01

    The spectrum of bromine was studied in the region 450-1100 Å, using the beam-foil method with 6 MeV ions from a tandem accelerator. On the basis of isoelectronic extrapolations and theoretical calculations, 32 lines were classified as transitions between the 3p63d84s and 3p63d84p configurations of Co-like Br IX. Of the 16 possible 4s levels 13 have been located, and 11 new 4p levels have been added to the previously known ones. Only 4 of all the 4p levels (45 in total) remain to be found.

  7. [Gallium(III) protoporphyrin IX]2: a soluble diamagnetic model for malaria pigment.

    PubMed

    Bohle, D Scott; Dodd, Erin L

    2012-04-16

    Gallium(III) protoporphyrin IX forms a dimeric propionate-bridged dimer, 2, that is a soluble diamagnetic analogue of hematin anhydride. The single-crystal structure of 2 corresponds to a nondisordered inversion-symmetric dimer similar to malaria pigment but, unlike it, has a six-coordinate metal and an intraporphyrin rather than an interporphyrin hydrogen bond. NMR NOE correlations demonstrate the presence of the propionate linkage in solutions with pyridine. Taken together, this is the first single-crystal X-ray diffraction study of a propionate-linked dimer as found in malaria pigment and the first evidence for its presence in solution.

  8. Bilateral Cranial IX and X Nerve Palsies After Mild Traumatic Brain Injury

    PubMed Central

    Yoo, Seung Don; Kim, Dong Hwan; Lee, Seung Ah; Joo, Hye In; Yeo, Jin Ah

    2016-01-01

    We report a 57-year-old man with bilateral cranial nerve IX and X palsies who presented with severe dysphagia. After a mild head injury, the patient complained of difficult swallowing. Physical examination revealed normal tongue motion and no uvular deviation. Cervical X-ray findings were negative, but a brain computed tomography revealed a skull fracture involving bilateral jugular foramen. Laryngoscopy indicated bilateral vocal cord palsy. In a videofluoroscopic swallowing study, food residue remained in the vallecula and pyriform sinus, and there was reduced motion of the pharynx and larynx. Electromyography confirmed bilateral superior and recurrent laryngeal neuropathy. PMID:26949684

  9. 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.

  10. 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.

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

    SciTech Connect

    Solera, J. ); Magallon, 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[prime] end of intron d and the two last coding nucleotides located at the 3[prime] end of exon IV in the normal factor IX gene; this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment.

  12. 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.

  13. Antigen capsid-display on human adenovirus 35 via pIX fusion is a potent vaccine platform

    PubMed Central

    van der Helm, Esmeralda; Spek, Dirk; Vorthoren, Lars; Serroyen, Jan; Kuipers, Harmjan; Schuitemaker, Hanneke; Zahn, Roland; Custers, Jerome; Vellinga, Jort

    2017-01-01

    Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings. PMID:28362809

  14. In Vitro Dynamic Visualization Analysis of Fluorescently Labeled Minor Capsid Protein IX and Core Protein V by Simultaneous Detection

    PubMed Central

    Ugai, Hideyo; Wang, Minghui; Le, Long P.; Matthews, David A.; Yamamoto, Masato; Curiel, David T.

    2009-01-01

    Oncolytic adenoviruses represent a promising therapeutic medicine for human cancer therapy, but successful translation to human clinical trials requires careful evaluation of these viral characteristics. While the function of the adenovirus proteins have been analyzed in detail, the dynamics of adenovirus infection remain largely unknown due to technological constraints which prevent adequate tracking of the adenovirus particles after infection. Fluorescent labeling of the adenoviral particles is one new strategy designed to directly analyze dynamic processes of viral infection in virus-host cell interactions. We hypothesized that the double labeling technique of adenovirus with fluorescent proteins would allow us to properly analyze intracellular viruses and the fate of viral proteins in live analysis of adenovirus as compared to a single labeling. Thus, we generated a fluorescently labeled adenovirus with both a red fluorescent minor capsid protein IX (pIX-mRFP1) and a green fluorescent minor core protein V (pV-EGFP), resulting in Ad5-IX-mRFP1-E3-V-EGFP. The fluorescent signals for pIX-mRFP1 and pV-EGFP were detected within 10 min in living cells. However, the growth curve analysis of Ad5-IX-mRFP1-E3-V-EGFP showed approximately 150-fold reduced production of the viral progeny at 48 hours post-infection (h.p.i.) as compared to Ad5. Interestingly, pIX-mRFP1 and pV-EGFP were initially localized in the cytoplasm and the nucleolus, respectively, at 18 h.p.i. These proteins were observed in the nucleus during the late stage of infection and the relocalization of the proteins was observed in an adenoviral replication-dependent manner. These results indicate that the simultaneous detection of adenovirus using dual-fluorescent proteins is suitable for real-time analysis, including identification of infected cells, and monitoring viral spread, which will be required for complete evaluation of oncolytic adenoviruses. PMID:19853616

  15. Expression pattern and intensity of protoporphyrin IX induced by liposomal 5-aminolevulinic acid in rat pilosebaceous unit throughout hair cycle.

    PubMed

    Han, Insook; Jun, Mee Sook; Kim, Soo-Kyun; Kim, Moonkyu; Kim, Jung Chul

    2005-11-01

    We have developed liposomal formulation of 5-aminolevulinic acid (ALA) to enhance topical delivery and examined ALA-induced protoporpyrin (PpIX) expression in rat pilosebaceous unit throughout hair cycle. Two types of liposomes--glycerol dilaulate (GDL) and phosphatidylcholine (PC)--were formulated and both liposomal ALA increased PpIX expression in rat dorsal skin and pilosebaceous units when compared with free ALA. However, iontophoresis combined with liposomal ALA reduced the expression intensity of PpIX in hair bulbs although it achieved deeper and wider expression of PpIX through transfollicular pathway. After topical application in intact or depilated rat skin, liposomal ALA produced excellent PpIX expression in pilosebaceous units. The expression pattern and intensity of PpIX changed in hair cycle-dependent manner: specific expression only in sebaceous glands was observed at telogen; strong expression in whole pilosebaceous units was shown at anagen with intense expressions in hair bulbs and sebaceous glands; and a pattern similar to anagen but reduced intensity in the hair bulbs was seen at catagen. Throughout hair cycle, the expression pattern and intensity were dramatically changed in hair follicular epithelial cells depending on the cell density and proliferation activity of those cells, whereas those were consistent in sebaceous glands regardless of hair cycle. Little expression was shown in dermis. Photoactivation effect of 20% liposomal ALA-PDT using a red filtered-halogen lamp damaged sebaceous glands, hair follicles and epidermal layers. Formation of a thicker epidermal layer was observed, and hair induction after depilation was inhibited along with damage in sebaceous glands.

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

    PubMed

    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.

  17. No Evidence for Protoplanetary Disk Destruction By OB 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.

  18. Systemic delivery of factor IX messenger RNA for protein replacement therapy.

    PubMed

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B; Karmali, Priya P; Chivukula, Pad; Verma, Inder M

    2017-03-07

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4-6 h) that remains stable for up to 4-6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA-LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable.

  19. 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.

  20. 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

  1. 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.

  2. Systemic delivery of factor IX messenger RNA for protein replacement therapy

    PubMed Central

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

    2017-01-01

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

  3. 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.

  4. 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

  5. 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.

  6. CRC changes are no licence for inaction.

    PubMed

    Hobbs, Debra

    2011-05-01

    Last Autumn's Comprehensive Spending Review included what international environmental consultancy Environ describes as "an unexpected update" on the Carbon Reduction Commitment (CRC), with a change in its structure and timelines. Here Environ principal Debra Hobbs explains the implications for the healthcare estate, explains the steps organisations obligated under the scheme need to take over the next 3-4 years, and cautions them against "hitting the pause button".

  7. 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

    2011-08-07

    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.

  8. DISCLOSING THE INTERACTION OF CARBONIC ANHYDRASE IX WITH CULLIN-ASSOCIATED NEDD8-DISSOCIATED PROTEIN 1 BY MOLECULAR MODELING AND INTEGRATED BINDING MEASUREMENTS.

    PubMed

    Buonanno, Martina; Langella, Emma; Zambrano, Nicola; Succoio, Mariangela; Sasso, Emanuele; Alterio, Vincenzo; Di Fiore, Anna; Sandomenico, Annamaria; Supuran, Claudiu T; Scaloni, Andrea; Monti, Simona Maria; De Simone, Giuseppina

    2017-04-07

    Human Carbonic Anhydrase (hCA) IX is a membrane-associated member of the CA enzyme family, involved in solid tumor acidification. This enzyme is a marker of tumor hypoxia and a prognostic factor for several human cancers. In a recent paper we showed that CA IX interacts with cullin-associated NEDD8-dissociated protein 1 (CAND1), a nuclear protein involved in gene transcription and assembly of SCF ubiquitin ligase complexes. A functional role for this interaction was also identified, since lower CA IX levels were observed in cells with decreased CAND1 expression via shRNA-mediated interference. In this paper, we describe the identification of the structural determinants responsible of the CA IX/CAND1 interaction by means of a multidisciplinary approach, consisting of binding assay measurements, molecular docking and site-directed mutagenesis. These data open a novel scenario in the design of anticancer drugs targeting CA IX. Indeed, the knowledge of the structural determinants responsible for the CAND1/CA IX interaction provides the molecular basis to design molecules able to destabilize it. Due to the proposed function of CAND1 in stabilizing CA IX, these molecules could represent an efficient tool to lower the amount of CA IX in hypoxic cancer cells, thus limiting its action in survival and metastatic spread of tumors.

  9. 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

    ... 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 Windpower Development, LLC, TGP Development... 385.207, Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind...

  10. 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.

  11. The C-Terminal Domains of Adenovirus Serotype 5 Protein IX Assemble into an Antiparallel Structure on the Facets of the Capsid▿

    PubMed Central

    Fabry, Céline M. S.; Rosa-Calatrava, Manuel; Moriscot, Christine; Ruigrok, Rob W. H.; Boulanger, Pierre; Schoehn, Guy

    2009-01-01

    Adenovirus serotype 5 protein IX (pIX) has two domains connected by a flexible linker. Three N-terminal domains form triskelions on the capsid facets that cement hexons together, and the C-terminal domains of four monomers form complexes toward the facet periphery. Here we present a cryoelectron microscopy structure of recombinant adenovirus with a peptide tag added to the C terminus of pIX. The structure, made up by several C termini of pIX, is longer at both ends than the wild-type protein, and Fabs directed against the tag bind to both ends of the oligomer, demonstrating that the pIX C termini associate in an antiparallel manner. PMID:19004948

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

    PubMed

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

    2016-09-01

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

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

    SciTech Connect

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

    2015-09-23

    Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO2to 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, anRcryst of 18.0% and anRfree of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.

  14. 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

  15. Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates.

    PubMed

    Innocenti, Alessio; Vullo, Daniela; Scozzafava, Andrea; Casey, Joseph R; Supuran, Claudiut

    2005-02-01

    A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes with carboxylates including aliphatic (formate, acetate), dicarboxylic (oxalate, malonate), hydroxy/keto acids (l-lactate, l-malate, pyruvate), tricarboxylic (citrate), or aromatic (benzoate, tetrafluorobenzoate) representatives, some of which are important intermediates in the Krebs cycle, is presented. The cytosolic isozyme hCA I was strongly activated by acetate, oxalate, pyruvate, l-lactate, and citrate (K(A) around 0.1 microM), whereas formate, malonate, malate, and benzoate were weaker activators (K(A) in the range 0.1-1mM). The cytosolic isozyme hCA II was weakly inhibited by all the investigated anions, with inhibition constants in the range of 0.03-24 mM. The membrane-associated isozyme hCA IV was the most sensitive to inhibition by carboxylates, showing a K(I) of 99 nM for citrate and oxalate, of 2.8 microM for malonate and of 14.5 microM for pyruvate among others. The mitochondrial isozyme hCA V was weakly inhibited by all these carboxylates (K(I)s in the range of 1.67-25.9 mM), with the best inhibitor being citrate (K(I) of 1.67 mM), whereas this is the most resistant CA isozyme to pyruvate inhibition (K(I) of 5.5mM), which may be another proof that CA V is the isozyme involved in the transfer of acetyl groups from the mitochondrion to the cytosol for the provision of substrate(s) for de novo lipogenesis. Furthermore, the relative resistance of CA V to inhibition by pyruvate may be an evolutionary adaptation of this mitochondrial isozyme to the presence of high concentrations of this anion within this organelle. The transmembrane, tumor-associated isozyme hCA IX was similar to isozyme II in its slight inhibition by all these anions (K(I) in the range of 1.12-7.42 mM), except acetate, lactate, and benzoate, which showed a K(I)>150 mM. The lactate insensitivity of CA IX also represents an interesting finding, since it is presumed that this isozyme evolved in such a way as to

  16. 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).

  17. Survey of the anti-factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay.

    PubMed

    Boylan, B; Rice, A S; Neff, A T; Manco-Johnson, M J; Kempton, C L; Miller, C H

    2016-10-01

    Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen-Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB.

  18. 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…

  19. 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…

  20. Sexual Abuse of Students: Actual Notice and Deliberate Indifference; The Supreme Court's Title IX Standard for School District Liability.

    ERIC Educational Resources Information Center

    DeMitchell, Todd A.

    1998-01-01

    Explores the recent Supreme Court Decision ("Gebser v. Lago Vista Independent School District") on the liability standard Title IX imposes on school districts for the sexual abuse of a student by a teacher. Because the standard of actual knowledge and deliberate indifference by a school official is too high, the student is denied access…

  1. Characterization of genotype IX Newcastle disease virus strains isolated from wild birds in the northern Qinling Mountains, China.

    PubMed

    Duan, Xuji; Zhang, Peng; Ma, Jing; Chen, Shengli; Hao, Huafang; Liu, Haijin; Fu, Xiangjing; Wu, Pengpeng; Zhang, Dingquan; Zhang, Weidong; Du, Enqi; Yang, Zengqi

    2014-02-01

    This study was conducted to evaluate the virulence and evolution of genotype IX Newcastle disease virus (NDV) isolates obtained from wild birds in the northern Qinling Mountains of China. Five isolates were obtained from 374 larynx and cloacae swabs, which were collected from multiple asymptomatic wild bird species from August 2008 to July 2011, and were subsequently characterized by pathotype and genotype. Deduced amino acid sequences revealed that all five NDV isolates exhibited velogenic fusion protein cleavage sites motif (112)R-R-Q-R-R-F(117), shared as high as 99.8-99.9 % homology with each other, and varied in pathotype by intracerebral pathogenicity indices (ICPI) of 0.425-1.638. Phylogenetic analysis showed that all five isolates were clustered to genotype IX NDV. This is the first study to confirm multiple asymptomatic wild bird species as natural carriers of virulent genotype IX NDV. A novel NDV isolate from the Spotted-necked Dove (family Columbidae) exhibited discordance between its lentogenic ICPI and its virulent proteolytic cleavage site motif (112)R-R-Q-R-R-F(117). Although the five isolates underwent several amino acid mutations in the fusion protein, evidence of continuous evolutionary divergence did exist in the genotype IX NDV, which was always regarded as a conservative genotype.

  2. 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…

  3. Title IX Line: Vol. III, No. 1, Winter 1983 through Vol. V, No. 2, Spring/Summer 1985.

    ERIC Educational Resources Information Center

    Title IX Line, 1983

    1983-01-01

    "Title IX Line" is a periodic publication of The Center for Sex Equity in Schools, a desegregation assistance center funded by the U.S. Department of Education pursuant to Title IV of the 1964 Civil Rights Act. Each issue is devoted to a separate topic. This compilation of 9 sequential issues treats the follwoing themes: (1) vocational…

  4. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--Open-IX... Cooperative Research and Production Act of 1993, 15 U.S.C. Sec. 4301 et seq. (``the Act''),...

  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…

  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…

  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. Implementing Title IX. ACSA School Management Digest, Series 1, Number 8. ERIC/CEM Research Analysis Series, Number 35.

    ERIC Educational Resources Information Center

    Mazzarella, Jo Ann

    Title IX of the Education Amendments of 1972 and the HEW implementing regulations cover two major areas: sex discrimination in school courses, athletics, extracurricular activities, employment, and counseling, and sex descrimination in hiring, promotions, and benefits for school personnel. The author of this review examines the progress (and lack…

  9. 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.

  10. 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.

  11. 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

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Terms relating to other entities and concepts used throughout 12 CFR chapter IX. 900.3 Section 900.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.3 Terms...

  12. Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX for functional display on the virion

    SciTech Connect

    Li Jing; Le, Long; Sibley, Don A.; Mathis, J. Michael; Curiel, David T. . E-mail: david.curiel@ccc.uab.edu

    2005-08-01

    Adenoviral vectors have been exploited for a wide range of gene therapy applications. Direct genetic modification of the adenovirus capsid proteins has been employed to achieve alteration of vector tropism. We have defined the carboxy-terminus of the minor capsid protein pIX as a locus capable of presenting incorporated ligands on the virus capsid surface. Thus, we sought to exploit the possibility of incorporating functional proteins at pIX. In our current study, we incorporated the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) within pIX to determine if a larger protein of this type could retain functionality in this context. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional HSV-1 TK as a component of their capsid surface. DNA packaging and cytopathic effect were not affected by this genetic modification to the virus, while CAR-dependent binding was only marginally affected. Using an in vitro [{sup 3}H]-thymidine phosphorylation assay, we demonstrated that the kinase activity of the protein IX-TK fusion protein incorporated into adenoviral virions is functional. Analysis of cell killing after adenovirus infection showed that the protein IX-TK fusion protein could also serve as a therapeutic gene by rendering transduced cells sensitive to gancyclovir. Using 9-[4-[{sup 18}F]-fluoro-3-(hydroxymethyl)butyl]guanine ([{sup 18}F]-FHBG; a positron-emitting TK substrate), we demonstrated that we could detect specific cell binding and uptake of adenoviral virions containing the protein IX-TK fusion protein at 1 h post-infection. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional HSV-1 TK as a component of their capsid surface. The alternative display of HSV-1 TK on the capsid may offer advantages with respect to direct functional applications of this gene product. In addition, the determination of an expanded upper limit of incorporable

  13. Campus Sexual Misconduct: Restorative Justice Approaches to Enhance Compliance With Title IX Guidance.

    PubMed

    Koss, Mary P; Wilgus, Jay K; Williamsen, Kaaren M

    2014-07-01

    Campus response to sexual violence is increasingly governed by federal law and administrative guidance such as the 1972 Title IX, the 2011 Dear Colleague Letter (DCL), and the 2013 Violence Against Women Act. Educational institutions are directed to expand disciplinary responses and establish coordinated action to eliminate sexual violence and remedy its effects. Compliance fosters a quasi-criminal justice approach not suited to all sexual misconduct and inconsistent with developing practice in student conduct management. This article envisions restorative justice (RJ) enhancements to traditional student conduct processes that maintain compliance, expand options, empower victim choice, and increase responsiveness to DCL aims. The article (1) defines sexual violence and sexual harassment within the DCL scope, (2) elaborates the DCL position on permissible alternative resolutions and differentiates mediation from RJ, (3) sequences action steps from case report to finalization, including both restorative and traditional justice pathways; and (4) discusses building support for innovation beginning with existing campus response.

  14. Getting a Sporting Chance: Title IX and the Intergenerational Transmission of Health.

    PubMed

    Schulkind, Lisa

    2016-11-22

    We know that healthier mothers tend to have healthier infants, but we do not know how much of that relationship reflects the intergenerational transmission of genetic attributes versus environmental influences. From a policy perspective, it is crucial to understand which environmental influences are important and whether investments in one generation affect outcomes for the next. I use variation in the implementation of Title IX to measure the effects of increased athletic opportunities on the health of infants. Babies born to women with greater athletic opportunities as teenagers have babies that are healthier at birth. They are less likely to be born of low or very low birthweight and have higher Apgar scores. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Simulation of an IXS imaging analyzer with an extended scattering source

    SciTech Connect

    Suvorov, Alexey; Cai, Yong Q.

    2016-09-15

    A concept of an inelastic x-ray scattering (IXS) spectrograph with an imaging analyzer was proposed recently and discussed in a number of publications (see e.g. Ref.1). The imaging analyzer as proposed combines x-ray lenses with highly dispersive crystal optics. It allows conversion of the x-ray energy spectrum into a spatial image with very high energy resolution. However, the presented theoretical analysis of the spectrograph did not take into account details of the scattered radiation source, i.e. sample, and its impact on the spectrograph performance. Using numerical simulations we investigated the influence of the finite sample thickness, the scattering angle and the incident energy detuning on the analyzer image and the ultimate resolution.

  16. Protein secondary-shell interactions enhance the photoinduced hydrogen production of cobalt protoporphyrin IX.

    PubMed

    Sommer, Dayn Joseph; Vaughn, Michael David; Ghirlanda, Giovanna

    2014-12-28

    Hydrogen is an attractive fuel with potential for production scalability, provided that inexpensive, efficient molecular catalysts utilizing base metals can be developed for hydrogen production. Here we show for the first time that cobalt myoglobin (CoMyo) catalyzes hydrogen production in mild aerobic conditions with turnover number of 520 over 8 hours. Compared to free Co-protoporphyrin IX, incorporation into the myoglobin scaffold results in a 4-fold increase in photoinduced hydrogen production activity. Engineered variants in which specific histidine resides in proximity of the active site were mutated to alanine result in modulation of the catalytic activity, with the H64A/H97A mutant displaying activity 2.5-fold higher than wild type. Our results demonstrate that protein scaffolds can augment and modulate the intrinsic catalytic activity of molecular hydrogen production catalysts.

  17. Atomic and electronic structure of Mo6S9-xIx nanowires

    NASA Astrophysics Data System (ADS)

    Meden, A.; Kodre, A.; Padeznik Gomilsek, J.; Arcon, I.; Vilfan, I.; Vrbanic, D.; Mrzel, A.; Mihailovic, D.

    2005-09-01

    Moybdenum-based subnanometre diameter nanowires are easy to synthesize and disperse, and they exhibit a variety of functional properties in which they are superior to other one-dimensional materials. However, further progress in the understanding of physical properties and the development of new and specific applications have so far been impeded by the fact that their structure was not accurately known. Here we report on a combination of systematic x-ray diffraction and extended x-ray absorption fine structure experiments, and first-principles theoretical structure calculations, which are used to determine the atomic skeletal structure of individual Mo6S9-xIx (MoSIx) nanowires, their packing arrangement within bundles and their electronic band structure. From this work we conclude that the variations in functional properties appear to arise from different stoichiometry, not skeletal structure. A supplementary data file is available from http://stacks.iop.org/0957-4484/16/1578

  18. Potato chromosomes IX and XI carry genes for resistance to potato virus M.

    PubMed

    Marczewski, W; Strzelczyk-Zyta, D; Hennig, J; Witek, K; Gebhardt, C

    2006-05-01

    Two new loci for resistance to potato virus M (PVM), Gm and Rm, have been mapped in potato. The gene Gm was derived from Solanum gourlayi, whereas, Solanum megistacrolobum is the source of the gene Rm. Gm confers resistance to PVM infection after mechanical inoculation. Rm induces a hypersensitive response in potato plants. Two diploid populations segregating for Gm and Rm, bulked segregant analysis (BSA) using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR), and available potato molecular maps were instrumental for mapping the resistance loci. The novel locus Gm was mapped to a central region on potato chromosome IX. The locus Rm was placed on the short arm of chromosome XI, close to the marker loci GP250 and GP283, where a hotspot for monogenic and polygenic resistance to diverse pathogens is located in the potato and tomato genome.

  19. 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.

  20. 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.

  1. 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.

  2. The complementary roles of observation and experiment: Theodosius Dobzhansky's Genetics of Natural Populations IX and XII.

    PubMed

    Rudge, D W

    2000-01-01

    Theodosius Dobzhansky has long been recognized by historians as a pioneer in the combining of the 'field natural history' and 'laboratory experimentalist' traditions in biology (Allen 1994). The following essay analyzes two papers in his well-known Genetics of Natural Populations series, GNP IX and GNP XII, which demonstrate how Dobzhansky combined field and laboratory work in the pursuit of an evolutionary question. The analysis reveals the multiple and complementary roles field observations and experiments played in his investigations. But it also identifies several interpretive problems associated with the use of intervention that limited the effectiveness of his approach. The essay argues that these problems reflect a fundamental tension between the amount of control Dobzhansky had over the circumstances of his experiments and the applicability of his results to natural populations. It concludes that this trade-off represents an important distinction between experiments in biology and most other sciences.

  3. 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?

  4. 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.

  5. 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.

  6. 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.

  7. Chapter 13: Carbonic Anhydrase IX as an Imaging and Therapeutic Target for Tumors and Metastases

    PubMed Central

    Tafreshi, Narges K.; Lloyd, Mark C.; Bui, Marilyn M.; Gillies, Robert J.; Morse, David L.

    2014-01-01

    Carbonic anhydrase IX (CAIX) which is a zinc containing metalloprotein, efficiently catalyzes the reversible hydration of carbon dioxide. It is constitutively up-regulated in several cancer types and has an important role in tumor progression, acidification and metastasis. High expression of CAIX generally correlates with poor prognosis and is related to a decrease in the disease-free interval following successful therapy. Therefore, it is considered as a prognostic indicator in oncology. In this review, we describe CAIX regulation and its role in tumor hypoxia, acidification and metastasis. In addition, the molecular imaging of CAIX and its potential for use in cancer detection, diagnosis, staging, and for use in following therapy response is discussed. Both antibodies and small molecular weight compounds have been used for targeted imaging of CAIX expression. The use of CAIX expression as an attractive and promising candidate marker for systemic anticancer therapy is also discussed. PMID:24146382

  8. Induction of aminolevulinic acid synthase gene expression and enhancement of metabolite, protoporphyrin IX, excretion by organic germanium.

    PubMed

    Nakamura, Takashi; Saito, Miki; Shimada, Yasuhiro; Fukaya, Haruhiko; Shida, Yasuo; Tokuji, Yoshihiko

    2011-02-25

    Poly-trans-[(2-carboxyethyl) germasesquioxane], Ge-132 is a water-soluble organic germanium compound. Oral intake of dietary Ge-132 changes fecal color and we attempted to identify the fecal red pigment, which increased by the intake of dietary Ge-132. Sprague Dawley rats were given diets containing Ge-132 from 0 to 0.5% concentration. Fecal red pigment was extracted and purified for optical and structural studies. We examined the fecal red pigment content by high performance liquid chromatography (HPLC), and hepatic gene expressions relating to heme synthesis by reverse transcription polymerase chain reaction (RT-PCR). The purified red pigment had particular optical characteristics on the ultraviolet (UV)-visible spectrum (Soret band absorbance at 400 nm) and fluorescence emission at 600 nm by 400 nm excitation, and was identified as protoporphyrin IX by LC-MS analysis. Protoporphyrin IX significantly (P<0.05) increased 2.4-fold in the feces by the intake of a 0.5% Ge-132 diet. Gene expression analysis of the liver explained the increase of protoporphyrin IX by dietary Ge-132 as it enhanced (P<0.05) aminolevulinic acid synthase 1 (Alas1), a rate-limiting enzyme of heme synthesis, expression 1.8-fold, but decreased ferrochelatase (Fech) expression 0.6-fold (P<0.05). The results show that the intake of dietary Ge-132 is related to heme metabolism. Because protoporphyrin IX is used to treat chronic hepatitis, Ge-132 may be a beneficial substance to increase protoporphyrin IX in the liver.

  9. 5-Aminolevulinic acid-induced protoporphyrin-IX accumulation and associated phototoxicity in macrophages and oral cancer cell lines.

    PubMed

    Sharma, Sulbha; Jajoo, Anjana; Dube, Alok

    2007-09-25

    Studies were carried out on 5-aminolevulinic acid (ALA)-induced protoporphyrin (PpIX) synthesis in mice peritoneal macrophages and two human oral squamous cell carcinoma (OSCC) cell lines NT8e and 4451. Cells were treated with 200 microg/ml ALA for 15 h and PpIX accumulation was monitored by spectrofluorometry and phototoxicity to red light (630+/-20 nm) was measured by MTT assay. PpIX accumulation was higher in macrophages as compared to OSCC cells under both normal serum concentration (10%) and conditions of serum depletion. The results on phototoxicity measurements correlated well with the levels of PpIX accumulation in both macrophages and cancer cells. While red light caused 20% phototoxicity in macrophages, no phototoxicity was seen in 4451 cells at 10% serum. Decrease in serum concentration to 5% and 1% led to higher phototoxicity corresponding to 40% and 70% in macrophages and 10% and 15% in 4451 cells. Similar results were obtained in NT8e cell line. Propidium iodide staining followed by fluorescence microscopic observations on photodynamically treated co-culture of murine or human macrophages and cancer cells showed selective damage to macrophages. These results suggest that in OSCC, macrophages would contribute more to tumor PpIX level than tumor cells themselves and PDT may lead to selective killing of macrophages at the site of treatment. Since macrophages are responsible for production and secretion of various tumor growth mediators, the effect of selective macrophage killing on the outcome of PDT would be significant.

  10. 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.

  11. 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.

  12. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

    PubMed Central

    Al-Allaf, Faisal A.; Taher, Mohiuddin M.; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M.; Abalkhail, Halah A.; Owaidah, Tarek MA.

    2017-01-01

    Background Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. Methods For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Results Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. Conclusion The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia. PMID:28270892

  13. ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Peng, Qian; Sun, Chung-Ho; Sorensen, Dag R.; Carper, Steven W.; Madsen, Steen J.

    2005-04-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.

  14. 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.

  15. The NC2 domain of type IX collagen determines the chain register of the triple helix.

    PubMed

    Boudko, Sergei P; Bächinger, Hans Peter

    2012-12-28

    Precise mapping and unraveling the mechanism of interaction or degradation of a certain type of collagen triple helix requires the generation of short and stable collagenous fragments. This is a great challenge especially for hetero-trimeric collagens, where chain composition and register (stagger) are important factors. No system has been reported that can be efficiently used to generate a natural collagenous fragment with exact chain composition and desired chain register. The NC2 domain (only 35-50 residues) of FACIT collagens is a potent trimerization domain. In the case of type IX collagen it provides the efficient selection and hetero-trimerization of three distinct chains. The ability of the NC2 domain to determine the chain register of the triple helix is studied. We generated three possible sequence combinations (α1α1α2, α1α2α1, α2α1α1) of a type I collagen fragment (the binding region for the von Willebrand factor A3 domain) attached to the NC2 domain. In addition, two control combinations were produced that constitute homo-trimers of (α1)(3) or (α2)(3). For the hetero-trimeric constructs, α1α1α2 demonstrated a higher melting temperature than the other two. Binding experiments with the von Willebrand factor A3 domain revealed the homo-trimer of (α1)(3) as the strongest binding construct, whereas the homo-trimer of (α2)(3) showed no binding. For hetero-trimers, α1α1α2 was found to be the strongest binding construct. Differences in thermal stability and binding to the A3 domain unambiguously demonstrate that the NC2 domain of type IX collagen determines not only the chain composition but also the chain register of the adjacent triple helix.

  16. Sub-surface fluorescence imaging of Protoporphyrin IX with B-Scan mode tomography

    NASA Astrophysics Data System (ADS)

    Kepshire, Dax; Gibbs, Summer; Davis, Scott; Dehghani, Hamid; Paulsen, Keith D.; Pogue, Brian W.

    2006-02-01

    A non-contact fluorescence diffuse optical tomography (DOT) system capable of producing B-scan-type images of localized fluorescence regions up to depths of 15mm is presented. The B-Scan mode is analogous to ultrasound where the excitation and remission signals are delivered from the same surface of the tissue. This optical fluorescence system utilizes a 635 nm diode laser and two orthogonal galvanometers to raster scan the position of the source along the tissue surface. Using Protoporphyrin IX (PpIX) as a fluorescent agent, the amplitude of the remitted signal is separated by a 650 nm long pass filter and the fluorescence is then detected by a cooled CCD camera. Images are acquired for all source positions along the surface of the tissue, providing remission intensity images for each. This volume data set is then used in image reconstruction of the sub-surface volume, via a finite element method of modeling the fluorescence diffusion. The optimal remission imaging geometry, in terms of depth sensitivity, computation time, and image contrast-to-noise, was determined by performing sensitivity and singular-value decomposition analysis of the Jacobian for various source/detector combinations. The simulated results indicate that the fluorophore concentration and the inclusion size can not be recovered accurately in this mode; however, it is shown that the inclusion depth can accurately be predicted. Finally, by performing simulations on a mesh created from an MR image, we show that our system may prove useful in predicting the regions of local tissue fluorescence in the application of resection of residual brain tumor tissue under fluorescence guidance. This non-contact diagnostic system is being calibrated and finalized for potential use in this application of sub-surface imaging in the brain.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.

    PubMed Central

    Choo, K H; Raphael, K; McAdam, W; Peterson, M G

    1987-01-01

    Haemophilia B is a bleeding disorder caused by a functional deficiency of the clotting factor IX. A full length human factor IX complementary DNA clone containing all the natural mRNA sequences plus some flanking intron sequences was constructed with a metallothionein promoter and introduced into transgenic mice by microinjection into the pronuclei of fertilised eggs. The transgenic mice expressed high levels of messenger RNA, gamma-carboxylated and glycosylated protein, and biological clotting activity that are indistinguishable from normal human plasma factor IX. This study demonstrates the feasibility of expressing highly complex heterologous proteins in transgenic mice. It also provides the groundwork for the production of large amounts of human factor IX in larger transgenic livestock for therapeutic use, and the investigation of alternative genetic therapies for haemophilia B. Images PMID:3029708

  2. Extending the tissue penetration capability of conventional photosensitisers: a carbon quantum dot-protoporphyrin IX conjugate for use in two-photon excited photodynamic therapy.

    PubMed

    Fowley, Colin; Nomikou, Nikolitsa; McHale, Anthony P; McCaughan, Bridgeen; Callan, John F

    2013-10-11

    A carbon quantum dot (CQD)-protoporphyrin (IX) sensitisier conjugate was designed to exploit the large two-photon absorption cross section of CQDs and enable the indirect excitation of the sensitiser with 800 nm irradiation via FRET.

  3. 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

  4. 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

  5. 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

  6. Bianchi IX dynamics in bouncing cosmologies: homoclinic chaos and the BKL conjecture

    NASA Astrophysics Data System (ADS)

    Maier, Rodrigo; Damião Soares, Ivano; Valentino Tonini, Eduardo

    2015-12-01

    We examine the dynamics of a Bianchi IX model with three scale factors on a 4-dim Lorentzian brane embedded in a 5-dim conformally flat empty bulk with a timelike extra dimension. The matter content is a pressureless perfect fluid restricted to the brane, with the embedding consistently satisfying the Gauss-Codazzi equations. The 4-dim Einstein equations on the brane reduce to a 6-dim Hamiltonian dynamical system with additional terms (due to the bulk-brane interaction) that avoid the singularity and implement nonsingular bounces in the model. We examine the complex Bianchi IX dynamics in its approach to the neighborhood of the bounce which replaces the cosmological singularity of general relativity. The phase space of the model presents (i) two critical points (a saddle-center-center and a center-center-center) in a finite region of phase space, (ii) two asymptotic de Sitter critical points at infinity, one acting as an attractor to late-time acceleration and (iii) a 2-dim invariant plane, which together organize the dynamics of the phase space. The saddle-center-center engenders in the phase space the topology of stable and unstable 4-dim cylinders R × S 3, where R is a saddle direction and S 3 is the center manifold of unstable periodic orbits, the latter being the nonlinear extension of the center-center sector. By a proper canonical transformation the degrees of freedom of the dynamics are separated into one degree connected with the expansion/contraction of the scales of the model, and two rotational degrees of freedom associated with the center manifold S 3. The typical dynamical flow is thus an oscillatory mode about the orbits of the invariant plane. The stable and unstable cylinders are spanned by oscillatory orbits about the separatrix towards the bounce, leading to the homoclinic transversal intersection of the cylinders, as shown numerically in two distinct simulations. The homoclinic intersection manifold has the topology of R × S 2 consisting of

  7. Alternative splicing variants of carbonic anhydrase IX in human non-small cell lung cancer.

    PubMed

    Malentacchi, Francesca; Simi, Lisa; Nannelli, Caterina; Andreani, Matteo; Janni, Alberto; Pastorekova, Silvia; Orlando, Claudio

    2009-06-01

    In human cancers, carbonic anhydrase IX (CAIX) contributes to maintain intracellular and extracellular pH under hypoxic conditions, but also influences regulation of cell proliferation and tumor progression. CaIX was previously indicated as an independent prognostic marker in non-small cell lung carcinoma (NSCLC). Very recently a CAIX alternative splicing isoform, generating a transcript lacking of exons 8-9, was detected in cancer cells independently from the levels of hypoxia. This alternative splicing (AS) generates a truncated protein lacking the transmembrane region, the intracellular tail and the C-terminal of the catalytic domain and competes with the full-length (FL) isoform in the regulation of the extracellular pH, mainly in a mild hypoxic status. In the present study we measured the mRNA expression of FL and AS CAIX isoforms in 101 NSCLC and in paired not affected tissues. The two isoforms were coexpressed in all NSCLC and normal tissues but while AS mRNA was prevalent in normal tissues (66+/-3%), the FL isoform was higher in NSCLC (58+/-2%, p=0.001). FL mRNA, but not AS, was statistically increased in NSCLC (p=0.01) and showed a statistical association with lymphnode involvement (p=0.009) and tumor stage (p=0.04). Global survival analysis of cancer/related death showed that high levels of FL mRNA were predictive of unfavorable outcome (p<0.0001) and shorter disease-free survival (p<0.0001). Multivariate analysis indicated that FL is an independent prognostic factor for overall survival and higher levels of mRNA in NSCLC sensibly increase hazard ratio ( approximately sixfold). In conclusion, our results seems to indicate that, at least in NSCLC, FL CAIX is the most accurate surrogate of hypoxic stress and represents the only variant with a prognostic role. These data indicate the importance of a separate measurement of the two isoforms in cancer and the need of an accurate re-evaluation of most studies on the clinical role of CAIX in cancer diagnosis.

  8. Synthesis and biological evaluation of cyclic imides incorporating benzenesulfonamide moieties as carbonic anhydrase I, II, IV and IX inhibitors.

    PubMed

    Abdel-Aziz, Alaa A-M; Angeli, Andrea; El-Azab, Adel S; Abu El-Enin, Mohamed A; Supuran, Claudiu T

    2017-03-01

    A group of cyclic imides was synthesized by reaction of amino-substituted benzenesulfonamides with a series of acid anhydrides such as succinic, maleic, tetrahydrophthalic, pyrazine-2,3-dicarboxylic acid anhydride, and substituted phthalic anhydrides. The synthesized sulfonamides were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV and IX, involved in a variety of diseases among which glaucoma, retinitis pigmentosa, etc. Some of these sulfonamides showed effective inhibitory action (in the nanomolar range) against the cytosolic isoform hCA II and the transmembrane, tumor-associated one hCA IX, making them interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. hCA I and IV were on the other hand less inhibited by these sulfonamides, with inhibition constants in the micromolar range.

  9. Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome.

    PubMed

    Rivera, C E; Villagra, J; Riordan, M; Williams, S; Lindstrom, K J; Rick, M E

    2001-01-01

    We describe a new mutation in glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome (BSS). Sequencing of GPIX revealed a homozygous (T-->C) transition at nucleotide 1717 (GenBank/HUMGPIX/M80478), resulting in a Cys(8) (TGT)-->Arg (CGT) replacement in the mature peptide. DNA restriction enzyme analysis using BsaAI revealed that the patient was homozygous and that his parents were heterozygous for the defect. This mutation disrupts a putative disulphide bond between the Cys(8) and Cys(12) that would alter the secondary structure of GPIX and which probably accounts for the absence of the GPIb/IX/V complex from the platelet surface in this patient.

  10. 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.

  11. MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

    SciTech Connect

    Detappe, A; Rottmann, J; Kunjachan, S; Berbeco, R; Tillement, O

    2015-06-15

    Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM of nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.

  12. X-RAY OUTFLOWS AND SUPER-EDDINGTON ACCRETION IN THE ULTRALUMINOUS X-RAY SOURCE HOLMBERG IX X-1

    SciTech Connect

    Walton, D. J.; Harrison, F. A.; Miller, J. M.; Reis, R. C.; Fabian, A. C.; Roberts, T. P.; Middleton, M. J.

    2013-08-10

    Studies of X-ray continuum emission and flux variability have not conclusively revealed the nature of ultraluminous X-ray sources (ULXs) at the high-luminosity end of the distribution (those with L{sub X} {>=} 10{sup 40} erg s{sup -1}). These are of particular interest because the luminosity requires either super-Eddington accretion onto a black hole of mass {approx}10 M{sub Sun} or more standard accretion onto an intermediate-mass black hole. Super-Eddington accretion models predict strong outflowing winds, making atomic absorption lines a key diagnostic of the nature of extreme ULXs. To search for such features, we have undertaken a long, 500 ks observing campaign on Holmberg IX X-1 with Suzaku. This is the most sensitive data set in the iron K bandpass for a bright, isolated ULX to date, yet we find no statistically significant atomic features in either emission or absorption; any undetected narrow features must have equivalent widths less than 15-20 eV at 99% confidence. These limits are far below the {approx}>150 eV lines expected if observed trends between mass inflow and outflow rates extend into the super-Eddington regime and in fact rule out the line strengths observed from disk winds in a variety of sub-Eddington black holes. We therefore cannot be viewing the central regions of Holmberg IX X-1 through any substantial column of material, ruling out models of spherical super-Eddington accretion. If Holmberg IX X-1 is a super-Eddington source, any associated outflow must have an anisotropic geometry. Finally, the lack of iron emission suggests that the stellar companion cannot be launching a strong wind and that Holmberg IX X-1 must primarily accrete via Roche-lobe overflow.

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

    PubMed

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

    2010-10-01

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

  14. Transient accumulation of Mg-protoporphyrin IX regulates expression of PhANGs - New evidence for the signaling role of tetrapyrroles in mature Arabidopsis plants.

    PubMed

    Zhang, Zhong-Wei; Yuan, Shu; Feng, Hong; Xu, Fei; Cheng, Jian; Shang, Jing; Zhang, Da-Wei; Lin, Hong-Hui

    2011-05-01

    Genetic and physiological studies have revealed evidence for multiple signaling pathways by which the plastid exerts retrograde control over photosynthesis associated nuclear genes (PhANGs). It has been proposed that the tetrapyrrole pathway intermediate Mg-protoporphyrin IX (Mg-proto IX) acts as the signaling molecule in the pathways and accumulates in the chloroplasts and cytosol of the cell after treatment with the herbicide Norflurazon (NF). However, the role of Mg-Proto IX in plastid signaling has been challenged by two recent reports. In this paper, new evidence is presented supporting Mg-Proto IX as a plastid-signaling molecule in mature Arabidopsis seedlings. Fluorescence HPLC and confocal microscope observation verified that a short-term (<96h) NF treatment resulted in a large accumulation of Mg-Proto IX accompanying with Lhcb repression, whereas the long-term NF treatments caused marked changes of tetrapyrrole pools, while Lhcb expression was continuously repressed. These results may explain the discrepancies among different reports. Reactive oxygen species (ROS) eliminator treatments only partly reversed the NF-induced repression of Lhcb. Therefore, the NF generates both ROS signals and Mg-Proto IX signals. Furthermore, our data suggested that plastid signal transduction through plastid GUN1 protein is independent of tetrapyrrole export from the plastid.

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

    PubMed

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

    2009-01-01

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

  16. Noninvasive Optical Imaging of UV-Induced Squamous Cell Carcinoma in Murine Skin: Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX Production

    PubMed Central

    Rollakanti, Kishore R.; Anand, Sanjay; Davis, Scott C.; Pogue, Brian W.; Maytin, Edward V.

    2015-01-01

    Better noninvasive techniques are needed to monitor protoporphyrin IX (PpIX) levels before and during photodynamic therapy (PDT) of squamous cell carcinoma (SCC) of the skin. Our aim was to evaluate: (1) multispectral fluorescent imaging of ultraviolet light (UV)-induced cancer and precancer in a mouse model of SCC; (2) multispectral imaging and probe-based fluorescence detection as a tool to study Vitamin D (VD) effects on aminolevulinic acid (ALA)-induced PpIX synthesis. Dorsal skin of hairless mice was imaged weekly during a 24-week UV carcinogenesis protocol. Hot spots of PpIX fluorescence were detectable by multispectral imaging beginning at 14 weeks of UV exposure. Many hot spots disappeared after cessation of UV at week 20, but others persisted or became visible after week 20, and corresponded to tumors that eventually became visible by eye. In SCC-bearing mice pretreated with topical VD before ALA application, our optical techniques confirmed that VD preconditioning induces a tumor-selective increase in PpIX levels. Fluorescence-based optical imaging of PpIX is a promising tool for detecting early SCC lesions of the skin. Pretreatment with VD can increase the ability to detect early tumors, providing a potential new way to improve efficacy of ALA-PDT. PMID:26223149

  17. Retargeting of Adenovirus Vectors through Genetic Fusion of a Single-Chain or Single-Domain Antibody to Capsid Protein IX

    PubMed Central

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

    2010-01-01

    Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting. We show that scFv can be displayed on the capsid through genetic fusion to native pIX but that these molecules fail to retarget the virus, due to improper folding of the scFv. Redirecting expression of the fusion protein to the endoplasmic reticulum (ER) results in correct folding of the scFv and allows it to recognize its epitope; however, ER-targeted pIX-scFv was incorporated into the Ad capsid at a very low level which was not sufficient to retarget virus infection. In contrast, a pIX-sdAb construct was efficiently incorporated into the Ad capsid and enhanced virus infection of cells expressing the targeted receptor. Taken together, our data indicate that pIX is an effective platform for presentation of large targeting polypeptides on the surface of the virus capsid, but the nature of the ligand can significantly affect its association with virions. PMID:20631131

  18. Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Gibbs-Strauss, Summer L.; Yang, Harold H.; Khan Hekmatyar, S.; Jack Hoopes, P.; O'Hara, Julia A.; Kauppinen, Risto A.; Pogue, Brian W.

    2011-09-01

    The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 images positively predicted the presence of a tumor, confirmed by the GFP positive (GFP+) and hematoxylin and eosin positive (H&E+) ROIs. However, only the absolute T2 images had predictive power from controls in ROIs that were GFP+ but H&E negative. Additionally, PpIX fluorescence and T1W+Gd image contrast were linearly correlated in both the GFP+ (r = 0.79, p<1×10-8) and H&E+ (r = 0.74, p<0.003) ROIs. The trace diffusion images did not have predictive power or significance from controls. This study indicates that gadolinium contrast enhanced MR images can predict the presence of diffuse tumors, but PpIX fluorescence is a better predictor regardless of tumor vascularity.

  19. N-glycosylations of human α1,3-fucosyltransferase IX are required for full enzyme activity.

    PubMed

    Seelhorst, Katrin; Stacke, Christina; Ziegelmüller, Patrick; Hahn, Ulrich

    2013-05-01

    Human α1,3-fucosyltransferase IX catalyzes the transfer of l-fucose from guanosine diphosphate-β-L-fucose to N-acetyllactosamine, generating a Lewis X epitope, and is thereby involved in the synthesis of fucosylated cell surface glycoconjugates. It contains three putative N-glycosylation sites (Asn62, Asn101 and Asn153). The current study considers the functional role of these potential N-glycosylations within the enzyme. We produced truncated variants of human fucosyltransferase IX containing the soluble extracellular catalytic domain. To analyze the relevance of each N-glycosylation site, several genomic mutant DNAs encoding a glutamine (Gln/Q) instead of the asparagine residue were created prosperously using site-directed mutagenesis and subsequently expressed in Spodoptera frugiperda cells applying a baculovirus expression system. After production and purification of these variants of human FucT IX, the wild-type (wt) enzyme and the variants were characterized regarding their activity and kinetic properties. The variants showed lower activity than the wt FucT, whereas the individual N-glycosylation sites had different effects on the enzyme activity and kinetic parameters. While the single variant N62Q still showed ∼60% of wt activity and N101Q retained ∼30% activity, replacement of Asn153 by glutamine led to an almost complete loss of enzymatic activity. The same could be observed for variants missing two or more putative N-glycosylation sites, which indicated the importance of N-glycosylation for enzyme stability and activity.

  20. Charge-exchange X-ray emission of M82: Kα triplets of O VII, Ne IX and Mg XI

    NASA Astrophysics Data System (ADS)

    Liu, Jiren; Mao, Shude; Wang, Q. Daniel

    2011-07-01

    Starburst galaxies are primary feedback sources of mechanical energy and metals, which are generally measured from associated X-ray emission lines, assuming that they are from the thermal emission of the outflowing hot gas. Such line emission, however, can also arise from the charge-exchange X-ray emission (CXE) between highly ionized ions and neutral species. To understand the feedback of energy and metals, it is crucial to determine the origin of the X-ray emission lines and to distinguish the contributions from the CXE and the thermal emission. The origin of the lines can be diagnosed by the Kα triplets of He-like ions, because the CXE favours the intercombination and forbidden lines, while the thermal emission favours the resonance line. We analyse the triplets of O VII, Ne IX and Mg XI observed in the XMM-Newton reflection grating spectra of the starburst galaxy M82. The flux contribution of the CXE is 90, 50 and 30 per cent to the O VII, Ne IX and Mg XI triplets, respectively. Averaged over all the three triplets, the contribution of the CXE is ˜50 per cent of the total observed triplet flux. To correctly understand the hot outflow of starburst galaxies, it is necessary to include the CXE. Based on the measured CXE fluxes of the O VII, Ne IX and Mg XI triplets, we estimate the relative abundances of O, Ne and Mg of the outflow and find they are similar to the solar ratios.

  1. 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.

  2. 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%.

  3. The impact of low levels of collagen IX and pyridinoline on the mechanical properties of in vitro engineered cartilage.

    PubMed

    Yan, Dan; Zhou, Guangdong; Zhou, Xu; Liu, Wei; Zhang, Wen Jie; Luo, Xusong; Zhang, Lu; Jiang, Ting; Cui, Lei; Cao, Yilin

    2009-02-01

    The application of in vitro engineered cartilage has become a promising approach to repair cartilage defects. Nevertheless, the poor mechanical properties of in vitro engineered cartilage limit its potential for clinical applications. Studies have shown that the extracellular matrix (ECM) components are strongly correlated with the mechanical strength of engineered cartilage, but it remains unclear which components play a key role in determining the mechanical property of engineered cartilage. To address this issue, quantitative analyses of cartilage-specific components among native cartilage, in vivo and in vitro engineered cartilages were performed, and the correlation between various ECM molecules and Young's modulus was further analyzed. The results showed that many ECM molecules, such as highly sulphated glycosaminoglycan (GAG), collagens II, IX, and pyridinoline (PYR), contributed to the mechanical strength of cartilages. Further comparison between in vitro engineered cartilage and stress-stimulated in vitro engineered cartilage, known to have stronger mechanical properties, showed that only collagen IX and PYR, but not GAG and collagen II, were the key factors determining the mechanical properties of in vitro engineered cartilage. These results indicate that in vitro environment lacks the niche for enhancing collagen crosslinking that is mediated by collagen IX and PYR during cartilage formation. Thus, the discovery provides a clue for engineering strong cartilage in vitro in the future by enhancing the levels of these two molecules.

  4. Binding determinants of the small heat shock protein, αB-crystallin: recognition of the ‘IxI' motif

    PubMed Central

    Delbecq, Scott P; Jehle, Stefan; Klevit, Rachel

    2012-01-01

    Small heat shock proteins (sHSPs) play a central role in protein homeostasis under conditions of stress by binding partly unfolded, aggregate-prone proteins and keeping them soluble. Like many sHSPs, the widely expressed human sHSP, αB-crystallin (‘αB'), forms large polydisperse multimeric assemblies. Molecular interactions involved in both sHSP function and oligomer formation remain to be delineated. A growing database of structural information reveals that a central conserved α-crystallin domain (ACD) forms dimeric building blocks, while flanking N- and C-termini direct the formation of larger sHSP oligomers. The most commonly observed inter-subunit interaction involves a highly conserved C-terminal ‘IxI/V' motif and a groove in the ACD that is also implicated in client binding. To investigate the inherent properties of this interaction, peptides mimicking the IxI/V motif of αB and other human sHSPs were tested for binding to dimeric αB-ACD. IxI-mimicking peptides bind the isolated ACD at 22°C in a manner similar to interactions observed in the oligomer at low temperature, confirming these interactions are likely to exist in functional αB oligomers. PMID:23188086

  5. Fluorescently labeled substrates for monitoring α1,3-fucosyltransferase IX activity.

    PubMed

    Lunau, Nathalie; Seelhorst, Katrin; Kahl, Stefanie; Tscherch, Kathrin; Stacke, Christina; Rohn, Sascha; Thiem, Joachim; Hahn, Ulrich; Meier, Chris

    2013-12-16

    Fucosylation is often the final process in glycan biosynthesis. The resulting glycans are involved in a variety of biological processes, such as cell adhesion, inflammation, or tumor metastasis. Fucosyltransferases catalyze the transfer of fucose residues from the activated donor molecule GDP-β-L-fucose to various acceptor molecules. However, detailed information about the reaction processes is still lacking for most fucosyltransferases. In this work we have monitored α1,3-fucosyltransferase activity. For both donor and acceptor substrates, the introduction of a fluorescent ATTO dye was the last step in the synthesis. The subsequent conversion of these substrates into fluorescently labeled products by α1,3-fucosyltransferases was examined by high-performance thin-layer chromatography coupled with mass spectrometry as well as dual-color fluorescence cross-correlation spectroscopy, which revealed that both fluorescently labeled donor GDP-β-L-fucose-ATTO 550 and acceptor N-acetyllactosamine-ATTO 647N were accepted by recombinant human fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, respectively. Analysis by fluorescence cross-correlation spectroscopy allowed a quick and versatile estimation of the progress of the enzymatic reaction and therefore this method can be used as an alternative method for investigating fucosyltransferase reactions.

  6. Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups.

    PubMed Central

    Lubahn, D B; Lord, S T; Bosco, J; Kirshtein, J; Jeffries, O J; Parker, N; Levtzow, C; Silverman, L M; Graham, J B

    1987-01-01

    Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present--and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups. PMID:2884869

  7. 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.

  8. Carbonic anhydrase IX correlates with survival and is a potential therapeutic target for neuroblastoma.

    PubMed

    Ameis, Helen M; Drenckhan, Astrid; Freytag, Morton; Izbicki, Jakob R; Supuran, Claudiu T; Reinshagen, Konrad; Holland-Cunz, Stefan; Gros, Stephanie J

    2016-01-01

    Carbonic anhydrase IX (CAIX) is involved in pathological processes including tumorgenicity, metastases and poor survival in solid tumors. Twenty-two neuroblastoma samples of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated immunohistochemically for expression of CAIX. Results were correlated with clinical parameters and outcome. Neuroblastoma Kelly and SH-EP-Tet-21/N cells were examined for CAIX expression and inhibited with specific inhibitors, FC5-207A and FC8-325A. 32% of neuroblastoma tumors expressed CAIX. This was significantly associated with poorer survival. Kelly and SH-EP-Tet-21/N cells showed a major increase of CAIX RNA under hypoxic conditions. Proliferation of Kelly cells was significantly decreased by CAIX inhibitors, FC5-207A and FC8-325A, while proliferation of SH-EP-Tet-21/N cells was only significantly affected by FC8-325A. CAIX is a potent biomarker that predicts survival in neuroblastoma patients. CAIX-targeted therapy in neuroblastoma cell lines is highly effective and strengthens the potential of CAIX as a clinical therapeutic target in a selected patient collective.

  9. 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.

  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. Neutron contamination of Varian Clinac iX 10 MV photon beam using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Yani, S.; Tursinah, R.; Rhani, M. F.; Soh, R. C. X.; Haryanto, F.; Arif, I.

    2016-03-01

    High energy medical accelerators are commonly used in radiotherapy to increase the effectiveness of treatments. As we know neutrons can be emitted from a medical accelerator if there is an incident of X-ray that hits any of its materials. This issue becomes a point of view of many researchers. The neutron contamination has caused many problems such as image resolution and radiation protection for patients and radio oncologists. This study concerns the simulation of neutron contamination emitted from Varian Clinac iX 10 MV using Monte Carlo code system. As neutron production process is very complex, Monte Carlo simulation with MCNPX code system was carried out to study this contamination. The design of this medical accelerator was modelled based on the actual materials and geometry. The maximum energy of photons and neutron in the scoring plane was 10.5 and 2.239 MeV, respectively. The number and energy of the particles produced depend on the depth and distance from beam axis. From these results, it is pointed out that the neutron produced by linac 10 MV photon beam in a typical treatment is not negligible.

  12. Two Coregulated Efflux Transporters Modulate Intracellular Heme and Protoporphyrin IX Availability in Streptococcus agalactiae

    PubMed Central

    Fernandez, Annabelle; Lechardeur, Delphine; Derré-Bobillot, Aurélie; Couvé, Elisabeth; Gaudu, Philippe; Gruss, Alexandra

    2010-01-01

    Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia. This pathogen does not synthesize heme, but scavenges it from blood to activate a respiration metabolism, which increases bacterial cell density and is required for full virulence. Factors that regulate heme pools in S. agalactiae are unknown. Here we report that one main strategy of heme and protoporphyrin IX (PPIX) homeostasis in S. agalactiae is based on a regulated system of efflux using two newly characterized operons, gbs1753 gbs1752 (called pefA pefB), and gbs1402 gbs1401 gbs1400 (called pefR pefC pefD), where pef stands for ‘porphyrin-regulated efflux’. In vitro and in vivo data show that PefR, a MarR-superfamily protein, is a repressor of both operons. Heme or PPIX both alleviate PefR-mediated repression. We show that bacteria inactivated for both Pef efflux systems display accrued sensitivity to these porphyrins, and give evidence that they accumulate intracellularly. The ΔpefR mutant, in which both pef operons are up-regulated, is defective for heme-dependent respiration, and attenuated for virulence. We conclude that this new efflux regulon controls intracellular heme and PPIX availability in S. agalactiae, and is needed for its capacity to undergo respiration metabolism, and to infect the host. PMID:20421944

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

    PubMed

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

    2014-10-01

    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.

  14. The NC2 Domain of Collagen IX Provides Chain Selection and Heterotrimerization*

    PubMed Central

    Boudko, Sergei P.; Zientek, Keith D.; Vance, Jesse; Hacker, Jessica L.; Engel, Jürgen; Bächinger, Hans Peter

    2010-01-01

    The mechanism of chain selection and trimerization of fibril-associated collagens with interrupted triple helices (FACITs) differs from that of fibrillar collagens that have special C-propeptides. We recently showed that the second carboxyl-terminal non-collagenous domain (NC2) of homotrimeric collagen XIX forms a stable trimer and substantially stabilizes a collagen triple helix attached to either end. We then hypothesized a general trimerizing role for the NC2 domain in other FACITs. Here we analyzed the NC2 domain of human heterotrimeric collagen IX, the only member of FACITs with all three chains encoded by distinct genes. Upon oxidative folding of equimolar amounts of the α1, α2, and α3 chains of NC2, a stable heterotrimer with a disulfide bridge between α1 and α3 chains is formed. Our experiments show that this heterotrimerization domain can stabilize a short triple helix attached at the carboxyl-terminal end and allows for the proper oxidation of the cystine knot of type III collagen after the short triple helix. PMID:20507993

  15. Fluorescence tomography characterization for sub-surface imaging with protoporphyrin IX.

    PubMed

    Kepshire, Dax; Davis, Scott C; Dehghani, Hamid; Paulsen, Keith D; Pogue, Brian W

    2008-06-09

    Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or close to the surface and, perhaps most importantly, FDOT was able to recover specific depth information about the location of embedded regions. The results indicate that an optimal system for localizing embedded fluorescent regions should combine fluorescence reflectance imaging for high sensitivity and sub-surface tomography for depth detection, thereby allowing more accurate localization in all three directions within the tissue.

  16. 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

  17. 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.

  18. Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies.

    PubMed

    Kitchen, Steve; Tiefenbacher, Stefan; Gosselin, Robert

    2017-04-01

    The advent of modified factor VIII (FVIII) and factor IX (FIX) molecules with extended half-lives (EHLs) compared with native FVIII and FIX represents a major advance in the field of hemophilia care, with the potential to reduce the frequency of prophylactic injections and/or to increase the trough level prior to subsequent injections. Monitoring treatment through laboratory assays will be an important part of ensuring patient safety, including any tailoring of prophylaxis. Several approaches have been used to extend half-lives, including PEGylation, and fusion to albumin or immunoglobulin. Some of these modifications affect factor assays as routinely performed in hemophilia centers; so, laboratories will need to use FVIII and FIX assays which have been shown to be suitable on a product-by-product basis. For some products, there are marked differences between results obtained using one-stage or chromogenic assays and results obtained using different reagents in the one-stage assay. The laboratory should use an assay in which the recovery of the product closely aligns with the assay used by the pharmaceutical company to assign potency to the product, so that the units reported by the laboratory agree with those used to demonstrate efficacy of the product during clinical trials. Reported assay differences in relation to several of the EHL FVIII and FIX molecules will be reviewed in this article.

  19. Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors

    PubMed Central

    Faes, Seraina; Planche, Anne; Uldry, Emilie; Santoro, Tania; Pythoud, Catherine; Stehle, Jean-Christophe; Horlbeck, Janine; Letovanec, Igor; Riggi, Nicolo; Datta, Dipak; Demartines, Nicolas; Dormond, Olivier

    2016-01-01

    The inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) by chemical inhibitors, such as rapamycin, has demonstrated anti-cancer activity in preclinical and clinical trials. Their efficacy is, however, limited and tumors eventually relapse through resistance formation. In this study, using two different cancer mouse models, we identify tumor hypoxia as a novel mechanism of resistance of cancer cells against mTORC1 inhibitors. Indeed, we show that the activity of mTORC1 is mainly restricted to the non-hypoxic tumor compartment, as evidenced by a mutually exclusive staining pattern of the mTORC1 activity marker pS6 and the hypoxia marker pimonidazole. Consequently, whereas rapamycin reduces cancer cell proliferation in non-hypoxic regions, it has no effect in hypoxic areas, suggesting that cancer cells proliferate independently of mTORC1 under hypoxia. Targeting the hypoxic tumor compartment by knockdown of carbonic anhydrase IX (CAIX) using short hairpin RNA or by chemical inhibition of CAIX with acetazolamide potentiates the anti-cancer activity of rapamycin. Taken together, these data emphasize that hypoxia impairs the anti-cancer efficacy of rapalogs. Therapeutic strategies targeting the hypoxic tumor compartment, such as the inhibition of CAIX, potentiate the efficacy of rapamycin and warrant further clinical evaluation. PMID:27153561

  20. The nature of the antibody response to Yersinia enterocolitica serotype IX in cattle

    PubMed Central

    Corbel, M. J.

    1973-01-01

    The nature of the antibody response of cattle to the antigen of Yersinia enterocolitica IX cross-reacting with Brucella spp. was examined. Density-gradient ultracentrifugation, ion-exchange chromatography, antibody adsorption and elution and disulphide bond reduction tests showed that both 19 S IgM and 7 S IgG1 and IgG2 antibodies were produced in response to the cross-reacting antigen. The highest titres of cross-reacting antibodies were detected by the agglutination and Coombs antiglobulin tests. Production of complement-fixing and precipitating antibodies cross-reacting with Br. abortus was transient and high titres were not attained. In contrast, although infection with Br. abortus also evoked cross-reacting antibodies of the IgM and IgG classes, much higher titres were produced in the complement fixation and precipitation tests and these persisted for long periods. At all stages of the serological response to both organisms, the two infections could be differentiated by the quantitative Rose Bengal plate test. PMID:4198202