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Sample records for aaron yeow dfo

  1. 76 FR 22101 - Science Advisory Board Staff Office; Notification of a Public Teleconference of the Chartered...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ...), 5 U.S.C., App. 2. Pursuant to FACA and EPA policy, notice is hereby given that the SAB will hold a... site at http://yosemite.epa.gov/sab/sabproduct.nsf/fedrgstr_activites/Lead%20Paint%20Hazard%20Standards... will be limited to three minutes. Interested parties should contact Mr. Aaron Yeow, DFO, in...

  2. Brook Trout Back in Aaron Run

    EPA Pesticide Factsheets

    Following a series of acid mine drainage (AMD) projects funded largely by EPA’s Clean Water Act Section 319 non-point source program, the pH level in Aaron Run is meeting Maryland’s water quality standard – and the brook trout are back.

  3. Cognitive Therapist: A Dialogue with Aaron Beck.

    ERIC Educational Resources Information Center

    Weinrach, Stephen G.

    1988-01-01

    Presents interview with cognitive therapist Aaron Beck in which Beck describes cognitive therapy; the contributions of Freud, Maslow, Rogers, and Ellis; cultural, class, and gender issues; training of cognitive-behavior therapists; and the future direction of treatment of anxiety and depression. (ABL)

  4. The "Splendid Isolation" of Aaron T. Beck.

    PubMed

    Rosner, Rachael I

    2014-12-01

    Aaron T. Beck's Cognitive Therapy (CT) is a school of psychotherapy, conceived in the 1960s, that is celebrated by many clinicians for having provided the scientific antidote to all that was wrong with psychoanalysis. This essay situates the origins of CT in the crisis of legitimacy in psychiatry in the 1960s and 1970s, when, among many charges, psycho- analysts had to face the accusation that analysis was not adequately scientific. Beck actually began his career as both a psychoanalyst and an experimentalist. Contrary to common triumphalist accounts, Beck created CT to be a neutral space, not a partisan one, in turbulent times. Other notable psychoanalysts also sought compromise, rather than partisanship, to bridge the transition to biomedical science. The biographical approach of this essay to the origins of Beck's CT both situates him historiographically and articulates the complex experiences of a generation of psychoanalysts otherwise opaque to standard narratives.

  5. 4. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 ...

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

    4. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 SOUTH (REAR) AND WEST (SIDE) ELEVATIONS - Eagle Cafe, 2566 Powell Street (moved to Pier 39), San Francisco, San Francisco County, CA

  6. 3. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 ...

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

    3. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 EAST (SIDE) AND SOUTH (REAR) ELEVATIONS - Eagle Cafe, 2566 Powell Street (moved to Pier 39), San Francisco, San Francisco County, CA

  7. 2. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 ...

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

    2. Historic American Buildings Survey Aaron Gallup, Photographer September 1977 NORTH (FRONT) AND EAST (SIDE) ELEVATIONS - Eagle Cafe, 2566 Powell Street (moved to Pier 39), San Francisco, San Francisco County, CA

  8. Geophysicists: Jules Aarons (1921-2008)

    NASA Astrophysics Data System (ADS)

    Mendillo, Michael

    2009-03-01

    Jules Aarons, a pioneer in satellite radio beacon studies of the ionosphere, died peacefully at his home in Newton, Mass., on 21 November 2008 at age 87. When considering his college career, Jules was drawn toward the humanities, an interest subsequently redirected by his parents toward science as a more suitable way to earn a living, and then by the U.S. Army Air Corps toward radio technology as a more suitable way to win World War II. Both goals were readily accomplished, perhaps instilling in Jules the value of proper mentorship, that central aspect of his life that so dominates our recollections of him. After the war, and with a variety of options before him, Jules decided upon civilian government service at the U.S. Air Force's then new field station in Cambridge, Mass. This was the founding entity of the Air Force Cambridge Research Laboratory (AFCRL), and those five famous letters became identified with his professional career (1946-1981). With Russia's launch of Sputnik in 1957, the era of space-based radio communications began, and with it the need to understand the sporadic crackling and fading (``scintillations'') of radio transmissions from satellites to ground receiving stations. Wartime efforts also gave birth to radio astronomy. Jules fostered ways to fund the synergies he saw between the radio technologies of space science and those of ground-based radio astronomy in ways almost unimaginable today (and certainly not by former U.S. senator Mike Mansfield, whose 1973 amendment to the U.S. Congress's defense appropriations bill limited the financing of basic research by military agencies only to projects that have direct military consequences; the amendment resulted in a permanent restructuring of how U.S. Department of Defense (DOD) agencies fund university-based research).

  9. The 2009 Lindau Nobel Laureate Meeting: Aaron Ciechanover, Chemistry 2004

    PubMed Central

    Ciechanover, Aaron

    2009-01-01

    Aaron Ciechanover was born in Haifa, Israel in October 1947. He shared the Nobel Prize in Chemistry in 2004 with Avram Hershko and Irwin Rose for their discovery of ubiquitin-mediated protein degradation. When Ciechanover began his work on proteolysis, the field was outside the realm of scientific mainstream as many thought that the fundamental secrets relating to sequence specificity were relevant to the synthetic side, or code side. The notion that specific sequences could selectively guide a destructive process did not naturally occur to scientists including Ciechanover himself. The emergence of controversial evidence demonstrating a requirement for metabolic energy in intracellular protein degradation, refuted the idea that cellular proteolysis was an entirely exergonic process occurring in the lysosome and prompted Ciechanover, Hershko, and Rose to "launch an attack" on the system, in order to uncover true pathway. Later findings of Ciechanover and subsequent groups showed that not only was the process energy-dependent, but that 8% of the human genome is remarkably one large ubiquitin system. Following the recapitulation and reflection of his work, Ciechanover shares insights into his principal and philosophical approach to science and life altogether. The life and work of Aaron Ciechanover are deeply rooted and influenced by Judaism and Israel and it is therefore that with only brief intermission, Ciechanover spent his scientific career in Israel as he is - through his presence and work - able to contribute and shape presence and future of the State of Israel. PMID:19571788

  10. 75 FR 7044 - Samuel Aaron, Inc., Long Island City, NY; Notice of Negative Determination Regarding Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration Samuel Aaron, Inc., Long Island City, NY; Notice of Negative... requested administrative reconsideration of the Department's negative determination regarding eligibility...

  11. Culture in salutogenesis: the scholarship of Aaron Antonovsky

    PubMed Central

    Benz, Carina; Mittelmark, Maurice; Vaandrager, Lenneke

    2014-01-01

    Aaron Antonovsky wrote extensively, although disjointedly, about the roles of culture in salutogenesis. This paper provides a synopsis of his work in this arena. A literature review identified those of his English language writings in which culture was a subject, and relevant text segments were analysed using an inductive followed by a deductive method. Using thematic network analysis, text segments were sorted inductively by open coding and then analysed. This was followed by deductive text segment coding guided by the constructs of the salutogenic model of health. The analysis revealed that Antonovsky had an expansive interest in the roles of culture in salutogenesis. His writings included attention to the role of culture in: (a) shaping life situations; (b) giving rise to stressors and resources; (c) contributing to life experiences of predictability, load balance and meaningful roles; (d) facilitating the development of the sense of coherence and (e) shaping perceptions of health and well-being. Antonovsky’s writings about culture were sometimes conjectural, as well as being obviously influenced by his life experience in the USA and then in Israel, and by the spirit of the times in which he lived. However, he also drew extensively on his own and others’ empiricism, leading him to view culture as an integral aspect of the salutogenic model of health. The present analysis provides salutogenesis scholars with a roadmap of Antonovsky’s reflections, ponderings and conclusions about culture in the context of salutogenesis. It provides assistance in the form of an overview of Antonovsky’s treatment of culture in the context of salutogenesis. PMID:24814861

  12. Primary Disaster Field Office (DFO), Lufkin, Texas

    NASA Technical Reports Server (NTRS)

    Wetherbee, James D.

    2005-01-01

    On February 1, 2003, the Space Shuttle Columbia broke apart during atmospheric re-entry on mission STS-107; the complexity of such an event cannot be underestimated. The Lufkin Disaster Field Office (DFO) served as the primary DFO for all operations, including staging assets and deploying field teams for search, recovery and security. There were many organizations that had operational experience with disaster recovery. Offers to help came from many groups including the White House Liaison Office, the Department of Defense (DOD), branches of local, state and federal government, the Federal Bureau of Investigation (FBI), the Federal Emergency Management Agency (FEMA), the Environmental Protection Agency (EPA), state police, fire departments, the Texas Forestry Service, the Texas Army National Guard, medical groups, various rescue forces, contractor companies, the Salvation Army, local businesses, and citizens of our country and especially East Texas. The challenge was to know how much help to accept and how to efficiently incorporate their valuable assistance into a comprehensive and cohesive operational plan. There were more than 2,000 people involved with search and recovery.

  13. Future-Minded: Aaron Schmidt--Thomas Ford Memorial Library, IL

    ERIC Educational Resources Information Center

    Library Journal, 2005

    2005-01-01

    Like many young people, Aaron Schmidt loves electronic gadgets. But not for their own sake. He believes the future of libraries depends on how well we meet the needs of today's young adults, who are far more tech-fluent than most librarians. As reference librarian and all-around technology guru at Thomas Ford Memorial Library, Schmidt created the…

  14. Computational Science as Part of Technology Education: An Interview with Aaron Clark

    ERIC Educational Resources Information Center

    Technology Teacher, 2008

    2008-01-01

    As teachers search for the most appropriate form of TIDE education for the future, they must consider as many alternatives as possible. One such alternative is computational science, which is described in detail in this interview with Dr. Aaron Clark of North Carolina State University. Dr. Clark recently agreed to this interview, with the primary…

  15. Considering Pastoral Power: A Commentary on Aaron Schutz's "Rethinking Domination and Resistance: Challenging Postmodernism"

    ERIC Educational Resources Information Center

    Caughlan, Samantha

    2005-01-01

    In his "Rethinking Domination and Resistance: Challenging Postmodernism" ("Educational Researcher," January-February, 2004), Aaron Schutz questioned what he saw as postmodernism's fascination with the workings of pastoral modes of control, a preoccupation that prevents postmodernists from locating and opposing the disciplinary controls experienced…

  16. High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration.

    PubMed

    Lombardo, T; Ferro, G; Frontini, V; Percolla, S

    1996-01-01

    To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of i.v. therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the i.v. route.

  17. Electron-Molecule Col1isions: Quantitative Approaches, and the Legacy of Aaron Temkin

    NASA Technical Reports Server (NTRS)

    Schneider, B.I.

    2007-01-01

    This article, on electron-molecule collisions, is dedicated to the legacy of my good friend and sometime collaborator, Aaron Temkin on his retirement from the NASA-Goddard Space Flight Center after many years of work at the highest intellectual level in the theoretical treatment of electron-atom and electron-molecule scattering. Aaron's contributions to the manner in which we think about electron-molecule collisions is clear to all of us who have worked in this field. I doubt that the great progress that has occurred in the computational treatment of such complex collision problems could have happened without these contributions. For a brief historical account, see the discussion of Temkin's contribution to electron-molecule scattering in the first article of this volume by Dr. A. K. Bhatia. In this article, I will concentrate on the application of the so called, non-adiabatic R-matrix theory, to vibrational excitation and dissociative attachment, although I will also present some results applying the Linear Algebraic and Kohn-Variational methods to vibrational excitation. As a starting point for almost all computationally effective approaches to electron-molecule collisions, is the fixed nuclei approximation. That is, one recognizes, just as one does with molecular bound states, that there is a separation of electronic(fast) and nuclear(s1ow) degrees of freedom. This separation makes it possible to "freeze" the nuclei in space, calculate the collision parameters for the frozen molecule and then, somehow to add back the vibrations and rotations. The manner in which this is done, depends on the details of the collision problem. It is the work of Aaron and a number of other researchers that has provided the guidance necessary to resolve these issues.

  18. Desferal (DFO) induced Ga-67 washout from normal tissue, tumor and abscess in experimental animals

    SciTech Connect

    Oster, Z.H.; Som, P.; Atkins, H.L.; Brill, A.B.

    1980-01-01

    In the experimental animal, desferal (DFO) given intravenously washes out Ga-67 from all tissues. This effect is not uniform: blood activity is reduced very markedly, while liver activity is less affected. Maximal effect of DFO occurs if given close to the Ga-67 injection. When the time interval between the two is increased, the absolute amount of Ga-67 excreted in the urine in excess of the spontaneous excretion is reduced. Administration of DFO does not effect Ga-67 gastrointestinal excretion. In three animal tumor models (EMT-6 sarcoma in Balb/c mice, spontaneous adenocarcinoma in mice, and spontaneous adenocarcinoma in the rabbit) and in sterile abscess-bearing rats, the administration of DFO 24 hrs after Ga-67-citrate improves significantly the target-to-nontarget ratio. Animals given 50 mg/kg DFO I.V. after Ga-67 citrate showed a significant reduction in the whole-body activity as seen in a one-week follow up.

  19. Aaron T. Beck's drawings and the psychoanalytic origin story of cognitive therapy.

    PubMed

    Rosner, Rachael I

    2012-02-01

    In this essay the author challenges the standard origin story of cognitive therapy, namely, that its founder Aaron T. Beck broke with psychoanalysis to pursue a more pragmatic, parsimonious, and experimentalist cognitive model. It is true that Beck broke with psychoanalysis in large measure as a result of his experimental disconfirmation of key psychoanalytic ideas. His new school of cognitive therapy brought the experimental ethos into every corner of psychological life, extending outward into the largest multisite randomized controlled studies of psychotherapy ever attempted and inward into the deepest recesses of our private worlds. But newly discovered hand-sketched drawings from 1964 of the schema, a conceptual centerpiece of cognitive therapy, as well as unpublished personal correspondence show that Beck continued to think psychoanalytically even after he broke with psychoanalysis. The drawings urge us to consider an origin story much more complex than the one of inherited tradition. This new, multifaceted origin story of cognitive therapy reaches beyond sectarian disagreements and speaks to a broader understanding of the theoretical underpinnings of cognitive therapy.

  20. Effects of the Microbial Siderophore DFO-B on Pb and Cd Speciation in Aqueous Solution

    SciTech Connect

    Mishra, Bhoopesh; Haack, Elizabeth A.; Maurice, Patricia A.; Bunker, Bruce A.

    2009-04-08

    This study investigates the complexation environments of aqueous Pb and Cd in the presence of the trihydroxamate microbial siderophore, desferrioxamine-B (DFO-B) as a function of pH. Complexation of aqueous Pb and Cd with DFO-B was predicted using equilibrium speciation calculation. Synchrotron-based X-ray absorption fine structure (XAFS) spectroscopy at Pb L(III) edge and Cd K edge was used to characterize Pb and Cd-DFO-B complexes at pH values predicted to best represent each of the metal-siderophore complexes. Pb was not found to be complexed measurably by DFO-B at pH 3.0, but was complexed by all three hydroxamate groups to form a totally 'caged' hexadentate structure at pH 7.5-9.0. At the intermediate pH value (pH 4.8), a mixture of Pb-DFOB complexes involving binding of the metal through one and two hydroxamate groups was observed. Cd, on the other hand, remained as hydrated Cd{sup 2+} at pH 5.0, occurred as a mixture of Cd-DFOB and inorganic species at pH 8.0, and was bound by three hydroxamate groups from DFO-B at pH 9.0. Overall, the solution species observed with EXAFS were consistent with those predicted thermodynamically. However, Pb speciation at higher pH values differed from that predicted and suggests that published constants underestimate the binding constant for complexation of Pb with all three hydroxamate groups of the DFO-B ligand. This molecular-level understanding of metal-siderophore solution coordination provides physical evidence for complexes of Pb and Cd with DFO-B, and is an important first step toward understanding processes at the microbial- and/or mineral-water interface in the presence of siderophores.

  1. The role of Dr Isaac Aaron and the Australian Medical Journal in the dissemination of information about etherisation in the 1840s.

    PubMed

    Paull, J D

    2013-07-01

    Isaac Aaron (1804 to 1877), an ambitious young medical practitioner, arrived in Sydney from Britain in 1838 and was registered by the New South Wales Medical Board the following year. After contributing to the Australian Medical Journal, established in August 1846 by William Baker, he became the editor in December and acquired it in May the following year. Dr Pugh became the most prolific local contributor to the journal but he and the editor had a somewhat 'prickly' relationship. Aaron was very critical of etherisation when the first news arrived in Australia, but Pugh chose Aaron's journal in which to report his initial and subsequent experience with the technique. Aaron repeatedly appealed for experimental evidence and rational decision-making to determine the place of etherisation in medical practice. Unfortunately for Australian medicine, Aaron had to suspend the publication of the journal in October 1847, lacking both time and the support of the profession necessary to maintain it. This created an unanticipated adverse outcome for Dr Pugh.

  2. Aaron O. Wells, MD and the Medical Committee for Human Rights: reflections on a life of conscience.

    PubMed

    Wells, Aaron O

    2004-11-01

    The southern civil rights movement compelled Dr. Aaron Wells and other doctors to find ways to use their skills in support of that movement. Through the Medical Committee for Human Rights (MCHR), healthcare workers provided a medical presence for civil rights protesters in the south during the 1960s. Formed at a time when racial segregation in professional medical associations, hospitals, and medical education was common, the MCHR also highlighted race-based inequities in American medicine. Dr. Wells, a man who lives a life of activism, was the first national president of the MCHR. During the summer of 2002, nearly 40 years after the founding of MCHR, Wells was interviewed about his experiences. Those reminiscences are the basis of this article.

  3. Aaron O. Wells, MD and the Medical Committee for Human Rights: reflections on a life of conscience.

    PubMed Central

    Wells, Aaron O.

    2004-01-01

    The southern civil rights movement compelled Dr. Aaron Wells and other doctors to find ways to use their skills in support of that movement. Through the Medical Committee for Human Rights (MCHR), healthcare workers provided a medical presence for civil rights protesters in the south during the 1960s. Formed at a time when racial segregation in professional medical associations, hospitals, and medical education was common, the MCHR also highlighted race-based inequities in American medicine. Dr. Wells, a man who lives a life of activism, was the first national president of the MCHR. During the summer of 2002, nearly 40 years after the founding of MCHR, Wells was interviewed about his experiences. Those reminiscences are the basis of this article. Images p1520-a PMID:15586659

  4. DEFORMED FLORAL ORGAN1 (DFO1) regulates floral organ identity by epigenetically repressing the expression of OsMADS58 in rice (Oryza sativa).

    PubMed

    Zheng, Ming; Wang, Yihua; Wang, Yunlong; Wang, Chunming; Ren, Yulong; Lv, Jia; Peng, Cheng; Wu, Tao; Liu, Kai; Zhao, Shaolu; Liu, Xi; Guo, Xiuping; Jiang, Ling; Terzaghi, William; Wan, Jianmin

    2015-06-01

    Floral organ identity in plants is controlled by floral homeotic A/B/C/D/E-class genes. In Arabidopsis thaliana, several epigenetic repressors that regulate these floral organ identity genes have been characterized. However, the roles of epigenetic factors in rice floral development have not been explored in detail. Here, we report the identification and functional characterization of a rice epigenetic repressor, DEFORMED FLORAL ORGAN1 (DFO1) gene, which causes abnormal floral morphology when mutated. We isolated dfo1 by mapping, and confirmed its function by rescue experiments, combined with genetic, cytological and molecular biological analysis. We showed that DFO1 is constitutively expressed and encodes a nuclear-localized protein. Mutation of DFO1 causes the ectopic expression of C-class genes in the dfo1-1 mutant, and overexpression of OsMADS58, a C-class gene, phenocopies the dfo1 mutants. In vitro and in vivo experiments demonstrated that DFO1 interacts with the rice polycomb group (PcG) proteins (OsMSI1 and OsiEZ1). Remarkably, trimethylation of histone H3 lysine 27, a mark of epigenetic repression, is significantly reduced on OsMADS58 chromatin in the dfo1-1 mutant. Our results suggest that DFO1 functions in maintaining rice floral organ identity by cooperating with PcG proteins to regulate the H3K27me3-mediated epigenetic repression on OsMADS58.

  5. The Arabidopsis thaliana DSB formation (AtDFO) gene is required for meiotic double-strand break formation.

    PubMed

    Zhang, Cheng; Song, Yao; Cheng, Zhi-hao; Wang, Ying-xiang; Zhu, Jun; Ma, Hong; Xu, Ling; Yang, Zhong-Nan

    2012-10-01

    DNA double-strand break (DSB) formation is the initial event for meiotic recombination catalyzed by the conserved Spo11 protein. In Arabidopsis, several proteins have been reported to be involved in DSB formation. Here, we report an Arabidopsis DSB forming (DFO) gene in Arabidopsis that is involved in DSB formation. The dfo mutant exhibits reduced fertility, producing polyads with an abnormal number of microspores, unlike the tetrads in the wild type. The dfo meiocytes were defective in homologous chromosome synapsis and segregation. Genetic analysis revealed that the homologous recombination of Atdfo-1 is severely affected in meiotic prophase I. DFO encodes a protein without any known conserved domain. There was no homologue identified outside the plant kingdom, indicating that AtDFO is a plant-specific protein. AtMRE11 has been reported to be responsible for processing SPO11-generated DSBs. The Atmre11 mutant displays chromosome fragmentation during meiosis. However, the Atdfo Atmre11 double mutant had no such chromosome fragmentation, indicating that AtDFO is required for DSB formation.

  6. Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma

    PubMed Central

    Bibi, Haim; Vinokur, Vladimir; Waisman, Dan; Elenberg, Yigal; Landesberg, Amir; Faingersh, Anna; Yadid, Moran; Brod, Vera; Pesin, Jimy; Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

    2014-01-01

    Background Redox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma. Objective To examine the anti-inflammatory properties of a newly developed specific iron–chelating complex, Zn/Ga−DFO, in a mouse model of asthma. Materials and methods Asthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga−DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga−DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted. Results The amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections. Conclusion In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO. PMID:25009783

  7. Effects of citric acid and the siderophore desferrioxamine B (DFO-B) on the mobility of germanium and rare earth elements in soil and uptake in Phalaris arundinacea.

    PubMed

    Wiche, Oliver; Tischler, Dirk; Fauser, Carla; Lodemann, Jana; Heilmeier, Hermann

    2017-02-03

    Effects of citric acid and desferrioxamine B (DFO-B) on the availability of Ge and selected REEs (La, Nd, Gd, Er) to P. arundinacea were investigated. A soil dissolution experiment was conducted to elucidate the effect of citric acid and DFO-B at different concentrations (1 and 10 mmol l(-1) citric acid) on the release of Ge and REEs from soil. In a greenhouse plants of P. arundinacea were cultivated on soil and on sand cultures to investigate the effects of citric acid and DFO-B on the uptake of Ge and REEs by the plants. Addition of 10 mmol l(-1) citric acid significantly enhanced desorption of Ge and REEs from soil and uptake into soil-grown plants. Applying DFO-B enhanced the dissolution and the uptake of REEs, while no effect on Ge was observed. In sand cultures, presence of citric acid and DFO-B significantly decreased the uptake of Ge and REEs, indicating a discrimination of the formed complexes during uptake. This study clearly indicates that citric acid and the microbial siderophore DFO-B may enhance phytoextraction of Ge and REEs due to the formation of soluble complexes that increase the migration of elements in the rhizosphere.

  8. 'The world is full of big bad wolves': investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson.

    PubMed

    McGeachan, Cheryl

    2014-09-01

    In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing's work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing's time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laing's and Esterson's spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care.

  9. ‘The world is full of big bad wolves’: investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson

    PubMed Central

    2014-01-01

    In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing’s work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing’s time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laing’s and Esterson’s spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care. PMID:25114145

  10. Computer Simulation of Specificity for In Vivo Breast Cancer Diagnosis by Carbogen-Enhanced Differential `Femton' Oximetry (`DFO')

    NASA Astrophysics Data System (ADS)

    Maglich, Bogdan C.; Radovic, Anna Z.; Nalcioglu, Orhan; Shultis, J. K.; Solomon, C. J.

    2010-03-01

    We performed computer simulation study of noninvasive diagnosis by DFO of hypoxia in a 1 cm tumor in 10 cm breast. Unlike in vitro cases (previous Abstract), background γ's from non hypoxic tissue will mask tumor γ signal, thus true hypoxia Q = -0.9 will be observed as apparent Q' = - 0.1. We propose to amplify Q' by replacing air breathing with carbogen (O2 95%, CO2 5%) thus making use of vasco-constrictive property that carbogen breathing increases O in normal tissue 3-fold, while O in subcutaneous hypoxic tumors remains const. This enhances apparent Q' to -0.25, shown to be detectable by DFO with specificity 99%. Principle of Femto Onco Diagnostics with and w/o carbogen, will be tested on R3230 tumors in Fischer rats at UCI Center for Functional Onco Imaging. Our probe (`OncoSensor') requires imager guidance, except for palpable tumors.

  11. Dissolution Kinetics of Hausmannite in the Presence of the Siderophore, DFO-B

    NASA Astrophysics Data System (ADS)

    Pena, J.; Duckworth, O. W.; Sposito, G.

    2004-12-01

    Siderophores are organic ligands with a very high affinity for Fe(III) that have been shown to dissolve iron-(III) bearing minerals, thus increasing the bioavailability of this nutrient. Recent work also has shown that siderophores are capable of forming stable Mn (III) complexes in aqueous environments and that they can promote the dissolution of Mn (III)-bearing minerals such as manganite (γ -MnOOH). The goal of this study was to investigate the dissolution kinetics of the mineral, hausmannite, in the presence of desferrioxamine B (DFO-B), a common trihydroxamate siderophore, synthesized by fungi and bacteria, which may play a role in the reduction of soluble Mn (III) to Mn2^+. Hausmannite, a mixed-valence Mn (II, III) oxide mineral with the formula Mn3O4, is a proposed intermediate in the oxidation of Mn2^+ to thermodynamically stable MnO2. Hausmannite particles were synthesized and characterized by X-ray diffraction, BET specific surface area, and SEM imaging. The extent and rate of dissolution were measured as a function of pH and ligand concentration in batch reactors at 25 ± 3 ° C. Total Mn concentrations were measured by ICP-AES, while complexed-Mn (III) was measured using UV-Vis spectrophotometry. In the absence of the ligand, the greatest amount of total Mn in solution was observed at pH ≈ 5. There was a sharp decrease in the extent of dissolution at pH > 5, however, and no appreciable dissolution occurred at pH > 8. In the presence of DFO-B, ligand-promoted dissolution dominated at pH > 8, with more than 90 % of the ligand complexed within 1 hour after addition. Below pH ≈ 8, a complex combination of reductive, ligand-promoted, and proton-promoted dissolution was observed. Our study revealed that complex mechanisms are involved in the DFOB-promoted dissolution of hausmannite, with several dissolution pathways occurring simultaneously. The results presented herein may have implications for mineral weathering, the biogeochemical cycling of Fe and Mn

  12. Experimental In Vitro Test of Differential `Femton' Oximetry (`DFO') Principle for Noninvasive Quantitative Diagnosis of Hypoxia

    NASA Astrophysics Data System (ADS)

    Druey, Chris; Radovic, Anna Z.; Maglich, Bogdan C.

    2010-03-01

    We report a high-resolution measurement of feasibility of noninvasive diagnosis of hypoxia via difference in γ rates from n + O --> O + γ + n between tumor, O1, and normal tissue, O2, using λDB 1 fm neutrons (`femtons'), which `count' atoms unaffected by molecular bonds. Q = (O1 -O2)/O1 quantifies hypoxia (<0), oxia (>0), and healthy tissue (=0). Hypoxic breast/prostate tumors have -0.80> Q <-0.96. DNA nucleotides dAdenosine, dCytosine and Thymidine, differing by 1 O atom, were irradiated with 14 MeV n's. We observed 1 atom as 0.012 ± .004 (3σ) γ rate difference. This implies that DFO would diagnose stand alone hypoxia Q = -0.10 and -0.25 with specificity 95% and 99%, respectively. As benchmark, we measured relative genome lengths of 2 mammal tissues to be Q = -0.12 ± .02, vs. 0.1 expected. These data suggest Femton Onco Physics as path to needle-less biopsy.

  13. Aaron's Law Act of 2013

    THOMAS, 113th Congress

    Rep. Lofgren, Zoe [D-CA-19

    2013-06-20

    07/15/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  14. (89)Zr-DFO-AMG102 Immuno-PET to Determine Local HGF Protein Levels in Tumors for Enhanced Patient Selection.

    PubMed

    Price, Eric W; Carnazza, Kathryn E; Carlin, Sean D; Cho, Andrew; Edwards, Kimberly J; Sevak, Kuntal K; Glaser, Jonathan M; de Stanchina, Elisa; Janjigian, Yelena Y; Lewis, Jason S

    2017-03-09

    Objectives: The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as an 89Zr-based immuno-PET (positron emission tomography) imaging agent to non-invasively determine the local levels of HGF protein in tumors. As recent clinical trials of HGF targeting therapies have been largely unsuccessful in several different cancers (e.g., gastric, brain, lung), we have synthesized and validated 89Zr-DFO-AMG102 as a companion diagnostic for improved identification and selection of patients having high local levels of HGF in tumors. To date, patient selection has not been performed using the local levels of HGF protein in tumors. Methods: The chelator p-SCN-Bn-DFO was conjugated to AMG102, radiolabeling with 89Zr was performed in high radiochemical yields and purity (>99%), and binding affinity of the modified antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA) type binding assay. PET imaging, biodistribution, autoradiography and immunohistochemistry, and ex vivo HGF-ELISA experiments were performed in murine xenografts of U87MG (HGF positive (+), MET positive (+)), MKN45 (HGF negative (-), MET +), and 4 patient-derived xenografts (PDX, MET+, HGF unknown). Results: Tumor uptake of 89Zr-DFO-AMG102 at 120 h p.i. in U87MG xenografts (HGF+) was high (36.8 ± 7.8 % injected dose per gram (ID/g)), while uptake in MKN45 xenografts (HGF-) was 5.0 ± 1.3 %ID/g, and a control of non-specific human IgG 89Zr-DFO-IgG in U87MG tumors was 11.5 ± 3.3 %ID/g, demonstrating selective uptake in HGF+ tumors. Similar experiments performed in 4 different gastric cancer PDX models showed low uptake of 89Zr-DFO-AMG102 (~4-7 %ID/g), which corresponded with low HGF levels in these tumors (ex vivo ELISA). Autoradiography, immunohistochemical staining, and HGF-ELISA assays confirmed that elevated levels of HGF protein were only present in U87MG tumors, and that 89Zr-DFO-AMG102 uptake was closely correlated with HGF protein levels in tumors

  15. Novel DFO-functionalized mesoporous silica for iron sensing. Part 2. Experimental detection of free iron concentration (pFe) in urine samples.

    PubMed

    Alberti, Giancarla; Emma, Giovanni; Colleoni, Roberta; Pesavento, Maria; Nurchi, Valeria Marina; Biesuz, Raffaela

    2014-08-21

    Successful in vivo chelation treatment of iron(iii) overload pathologies requires that a significant fraction of the administered drug actually chelates the toxic metal. Increased mobilization of the iron(iii) in experiments on animals or humans, most often evaluated from urinary output, is usually used as an assessment tool for chelation therapy. Alternatively, the efficiency of a drug is estimated by calculating the complexing ability of a chelating agent towards Fe(iii). The latter is calculated by the pFe value, defined as the negative logarithm of the concentration of the free metal ion in a solution containing 10 μM total ligand and 1 μM total metal at a physiological pH of 7.4. In theory, pFe has to be calculated taking into account all the complexation equilibria involving the metal and the possible ligands. Nevertheless, complexation reactions in complex systems such as serum and urine may hardly be accurately modelled by computer software. The experimental determination of the bioavailable fraction of iron(iii) in biological fluids would therefore be of the utmost relevance in the clinical practice. The efficiency of the therapy could be more easily estimated as well as the course of overload pathologies. In this context, the aim of the present work was the development of a sensor to assess the free iron directly in biological fluids (urine) of patients under treatment with chelating agents. In the proposed device (DFO-MS), the strong iron chelator deferoxamine (DFO) is immobilized on the MCM-41 mesoporous silica. The characterization of the iron(iii) sorption on DFO-MS was undertaken, firstly in 0.1 M KNO3, then directly in urine samples, in order to identify the sorption mechanism. The stoichiometry of the reaction in the solid phase was found to be: with an exchange constant (average value) of log βex = 40(1). The application of DFO-MS to assess pFe in SPU (Simulating Pathology Urine) samples was also considered. The results obtained were very

  16. Aaron Wildavsky, Incrementalism, and Defense Budgeting: A Bibliographic Essay

    DTIC Science & Technology

    1994-03-01

    generally straight line increase, but defense has had a feast or famine profile. More recently defense has come to be portrayed as taking from the poor...can be upset and disciplined through this election process; Les Aspin gained the House Armed 7 Services Committee through this process and was...proliferation of committees involved in defense; Wildavsky counts ten involved in defense in the Senate and eleven in the House . These committees mean there

  17. Aaron's Solution, Instructor's Problem: Teaching Surface Analysis Using GIS

    ERIC Educational Resources Information Center

    Koch, Tom; Denike, Ken

    2007-01-01

    Teaching GIS is relatively simple, a matter of helping students develop familiarity with the software. Mapping as an aid to thinking is harder to instruct. This article presents a laboratory and lecture package developed to teach the utility of mapping in a course on spatial data analysis. Following a historical review of the use of surface…

  18. The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1).

    PubMed

    Chen, Zhiqiang; Zhang, Daohai; Yue, Fei; Zheng, Minhua; Kovacevic, Zaklina; Richardson, Des R

    2012-05-18

    The epithelial-mesenchymal transition (EMT) is a key step for cancer cell migration, invasion, and metastasis. Transforming growth factor-β (TGF-β) regulates the EMT and the metastasis suppressor gene, N-myc downstream-regulated gene-1 (NDRG1), could play a role in regulating the TGF-β pathway. NDRG1 expression is markedly increased after chelator-mediated iron depletion via hypoxia-inducible factor 1α-dependent and independent pathways (Le, N. T. and Richardson, D. R. (2004) Blood 104, 2967-2975). Moreover, novel iron chelators show marked and selective anti-tumor activity and are a potential new class of anti-metabolites. Considering this, the current study investigated the relationship between NDRG1 and the EMT to examine if iron chelators can inhibit the EMT via NDRG1 up-regulation. We demonstrated that TGF-β induces the EMT in HT29 and DU145 cells. Further, the chelators, desferrioxamine (DFO) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), inhibited the TGF-β-induced EMT by maintaining E-cadherin and β-catenin, at the cell membrane. We then established stable clones with NDRG1 overexpression and knock-down in HT29 and DU145 cells. These data showed that NDRG1 overexpression maintained membrane E-cadherin and β-catenin and inhibited TGF-β-stimulated cell migration and invasion. Conversely, NDRG1 knock-down caused morphological changes from an epithelial- to fibroblastic-like phenotype and also increased migration and invasion, demonstrating NDRG1 knockdown induced the EMT and enhanced TGF-β effects. We also investigated the mechanisms involved and showed the TGF-β/SMAD and Wnt pathways were implicated in NDRG1 regulation of E-cadherin and β-catenin expression and translocation. This study demonstrates that chelators inhibit the TGF-β-induced EMT via a process consistent with NDRG1 up-regulation and elucidates the mechanism of their activity.

  19. 75 FR 32740 - Action Affecting Export Privileges; Aaron Robert Henderson and Valhalla Tactical Supply

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... codified at 50 U.S.C. app. Sec. Sec. 2401-2420 (2000). Since August 21, 2001, the EAA has been in lapse and... Emergency Economic Powers Act (50 U.S.C. 1701 et seq. (2000)). I have received notice of Henderson's... Order shall be published in the Federal Register. Issued this 28th day of May 2010. Bernard...

  20. 76 FR 66969 - Aaron Gloskowski, D.O.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... found in the sample, Registrant was directed by the Board to submit an observed urine test and hair test... Consent Order. GX H. Regarding ] Registrant's July 27, 2010 drug test, the Board found that while the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE...

  1. The antimalarial action of desferal involves a direct access route to erythrocytic (Plasmodium falciparum) parasites.

    PubMed Central

    Loyevsky, M; Lytton, S D; Mester, B; Libman, J; Shanzer, A; Cabantchik, Z I

    1993-01-01

    We designed the N-methylanthranilic-desferrioxamine (MA-DFO) as a fluorescent iron (III) chelator with improved membrane permeation properties. Upon binding of iron (III), MA-DFO fluorescence is quenched, thus allowing traceability of drug-iron (III) interactions. MA-DFO is well tolerated by mammalian cells in culture. Its antimalarial activity is pronounced: IC50 values on in vitro (24-h) growth of Plasmodium falciparum were 3 +/- 1 microM for MA-DFO compared with 30 +/- 8 for DFO. The onset of growth inhibition of rings or trophozoites occurs 2-4 h after exposure to 13 microM MA-DFO. This effect is commensurate with MA-DFO permeation into infected cells. In a 24-h exposure to MA-DFO or DFO, trophozoites take up either compound to approximately 10% of the external concentration, rings to 5%, and noninfected cells to < 1%. Red cells encapsulated with millimolar concentrations of DFO or MA-DFO fully support parasite invasion and growth. We conclude that extracellular MA-DFO and DFO gain selective access into parasites by bypassing the host. The rate-limiting step is permeation through the parasite membrane, which MA-DFO accomplishes faster than DFO, in accordance with its higher hydrophobicity. These views are consistent with the proposed duct, which apparently provides parasitized cells with a window to the external medium. PMID:8423220

  2. Developing an eXtensible Markup Language (XML) Application for DFO Marine Data Exchange via the Web

    DTIC Science & Technology

    2003-05-01

    XML). Le langage XML accepte le format ajouté et les restrictions de contenu dans ces éléments. Un schéma XML complet a été créé pour la structure...de contenu pour les séquences. Ces dernières étaient combinées en structures que l’on utilisait pour loger les données de profil des océans. Les...physical, chemical or biological analyses carried out on the data availability Pure Stores information about the possible release of the data to the

  3. An ESR study of the nitroxide radical of pentastarch-conjugated deferoxamine

    SciTech Connect

    Pieper, G.M.; Gross, G.J.; Kalyanaraman, B. )

    1990-01-01

    At higher concentrations, deferoxamine (DFO) reacts with hydroxyl radicals to produce a stable nitroxide free radical. Formation and decay of this nitroxide radical was investigated and compared with a novel modified pentastarch conjugate of DFO (MPS-DFO). Photolytic generation of hydroxyl radicals from H2O2 in the presence of free DFO produced a nitroxide radical with coupling constants of aN = 8.0 G and aH = 6.5 G. Under the same experimental conditions, equimolar concentrations of MPS-DFO produced an ESR signal of reduced intensity while iron-saturated MPS-DFO produced no signal. Incubation of free DFO with pentastarch (i.e., without conjugation) greatly decreased the intensity of the nitroxide radical signal. Using a spin-trapping technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), the pentastarch vehicle was shown to inhibit the DMPO-OH adduct formation. The decay of the DFO nitroxide radical decayed with a second-order rate constant while that of MPS-DFO decayed with a first-order rate constant. Thus, a novel derivative of DFO may provide some additional benefit in limiting DFO nitroxide radical formation and might explain the reported reduced in vivo toxicity of MPS-DFO relative to free DFO.

  4. A Democratic Vietnam; Not in the United States’ Core Interests

    DTIC Science & Technology

    2013-11-01

    Ibid., 16. 75. Aaron W. Steffens , Lieutenant Colonel, USAF, “Scramble in the South China Sea; Regional...Socialism in Comparative Perspective, Cambridge: Cambridge University Press, 2008 Steffens , Aaron W. Lieutenant Colonel, USAF “Scramble in the South

  5. 75 FR 61781 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the Subcommittee on Plant License Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ... the Designated Federal Official (DFO), Michael Benson (Telephone 301-415-6396 or e-mail Michael.Benson... the meeting. In addition, one electronic copy of each presentation should be emailed to the DFO...

  6. Eighth report of the Normandy Archaeological Project: 1975 excavations at the Eoff I site (40CF32), Aaron Shelton site (40CF69) and the Duke I site (40CF97)

    SciTech Connect

    Faulkner, C.H.; McCollough, C.R. . Dept. of Anthropology)

    1982-01-01

    This report discusses the research conducted during the last full field season for the Normandy Archaeological Project. There was a deep sense of urgency to use all available resources to continue to test crucial hypotheses about subsistence and settlement patterns of the Middle Woodland and Mississippian cultures in the lower and upper reservoir zones. The most salient of these hypotheses were prehistoric agricultural societies in the upper Duck Valley, and exploitative strategies of prehistoric hunters and gatherers in the upper Duck Valley differed in the lower and upper reservoir zones. Since the early Mississippian Banks phase and the late Middle Woodland Owl Hollow phase exhibited evidence for both food production and permanent settlement in the lower reservoir zone, a continued attempt was made to excavate those sites on which components of these two phase were found. Additional community pattern data and chronometric dates for the Banks phase were also sought since previously obtained radiocarbon assays indicated this was one of the earliest Mississippian cultures in the Middle South. The study of the origins and local development of this culture was also given priority status in Normandy Research. 145 refs., 33 figs., 94 tabs.

  7. Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels.

    PubMed

    Saito, Takashi; Tabata, Yasuhiko

    2014-08-01

    The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally.

  8. 76 FR 78329 - Commercial Space Transportation Advisory Committee; Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... contact Susan Lender, Designated Federal Officer (DFO), (the Contact Person listed below) by phone or... public may request a copy from Susan Lender, DFO (the Contact Person listed below). Interested members of... to submit written statements should contact Susan Lender, DFO, (the Contact Person listed below)...

  9. 75 FR 67718 - Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... submitted electronically to Eargle.Frances@epa.gov . Please contact the Designated Federal Officer (DFO) at... written request to the DFO. FOR FURTHER INFORMATION CONTACT: Frances Eargle, DFO for the Local Government Advisory Committee (LGAC) at (202) 564-3115 or e-mail at Eargle.frances@epa.gov. INFORMATION ON...

  10. Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect.

    PubMed

    Arantes, Jerusa Marilda; Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Silva, Maisa; Araújo, Márcio Sobreira Silva; de Carvalho, Andréa Teixeira; Pedrosa, Maria Lúcia; Carneiro, Cláudia Martins; Tafuri, Washington Luiz; Martins-Filho, Olindo Assis; Elói-Santos, Silvana Maria

    2011-08-01

    Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties.

  11. Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of oxidative stress in stroke patients.

    PubMed

    Selim, Magdy

    2010-03-01

    The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective effects, mediated via suppression of iron-induced hydroxyl radical formation, in various animal models of ischemic and hemorrhagic stroke. Therefore, the objective of this study was to investigate whether DFO can exert similar actions in stroke patients, by examining the effects of treatment with DFO on biological markers of oxidative stress, namely serum total hydroperoxides and lipoperoxides and total radical trapping antioxidant capacity (TRAP), in stroke patients. We found that serum levels of peroxides were reduced, and TRAP levels increased after a 3-day treatment with DFO (500 mg). These findings provide a preliminary proof of concept that DFO can exert potential antioxidant neuroprotective effects in stroke patients. Future, larger-scale, randomized, and controlled studies to further evaluate the safety and efficacy of DFO in patients with stroke are warranted.

  12. The Cyber Defense Review. Volume 1, Number 1, Spring 2016

    DTIC Science & Technology

    2016-04-20

    Kallberg The Decision to Attack: Military and Intelligence Cyber Decision - Making by Dr. Aaron F. Brantly The Cyber Defense Review...JAN KALLBERG 167 The Decision to Attack: Military and Intelligence Cyber Decision - Making by Dr. Aaron Brantly THE CYBER DEFENSE REVIEW VOL . 1...scientist, on Dr. Aaron Brantly’s brilliant and timely monograph, The Decision to Attack: Military and Intelligence Cyber Decision - Making . We hope you

  13. Effect of hydroxamate siderophores on Fe release and Pb(II) adsorption by goethite

    SciTech Connect

    Kraemer, Stephan M.; Cheah, Sing-Foong; Zapf, Rita; Xu, Jide; Raymond, Kenneth N.; Sposito, Garrison

    1998-08-01

    Hydroxamate siderophores are biologically-synthesized, Fe(III)-specific ligands which are common in soil environments. In this paper, we report an investigation of their adsorption by the iron oxyhydroxide, goethite; their influence on goethite dissolution kinetics; and their ability to affect Pb(II) adsorption by the goethite surface. The siderophores used were desferrioxamine B (DFO-B), a fungal siderophore, and desferrioxamine D1, an acetyl derivative of DFO-B (DFO-D1). Siderophore adsorption isotherms yielded maximum surface concentrations of 1.5 (DFO-B) or 3.5 (DFO-D1) mu-mol/g at pH 6.6, whereas adsorption envelopes showed either cation-like (DFO-B) or ligand-like (DFO-D1) behavior. Above pH 8, the adsorbed concentrations of both siderophores were similar. The dissolution rate of goethite in the presence of 240 mu M DFO-B or DFO-D1 was 0.02 or 0.17 mu-mol/g hr, respectively. Comparison of these results with related literature data on the reactions between goethite and acetohydroxamic acid, a monohydroxamate ligand, suggested that the three hydroxamate groups in DFO-D1 coordinate to Fe(III) surface sites relatively independently. The results also demonstrated a significant depleting effect of 240 mu-M DFO-B or DFO-D1 on Pb(II) adsorption by goethite at pH > 6.5, but there was no effect of adsorbed Pb(II) on the goethite dissolution rate.

  14. Effect of hydroxamate siderophores on Fe release and Pb(II) adsorption by goethite

    SciTech Connect

    Kraemer, S.M.; Cheah, S.F.; Zapf, R.; Xu, J.; Raymond, K.N.; Sposito, G.

    1999-10-01

    Hydroxamate siderophores are biologically-synthesized, Fe(III)-specific ligands which are common in soil environments. The authors report an investigation of their adsorption by the iron oxyhydroxide, goethite; their influence on goethite dissolution kinetics; and their ability to affect Pb(II) adsorption by the goethite surface. The siderophores used were desferrioxamine B (DFO-B), a fungal siderophore, and desferrioxamine D{sub 1}, an acetyl derivative of DFO-B (DFO-D1). Siderophore adsorption isotherms yielded maximum surface concentrations of 1.5 (DFO-B) or 3.5 (DFO-D1) {micro}mol/g at pH 6.6, whereas adsorption envelopes showed either cation-like (DFO-B) or ligand-like (DFO-D1) behavior. Above pH 8, the adsorbed concentrations of both siderophores were similar. The dissolution rate of goethite in the presence of 240 {micro}M DFO-B or DFO-D1 was 0.02 or 0.17 {micro}mol/g hr, respectively. Comparison of these results with related literature data on the reactions between goethite and acetohydroxamic acid, a monohydroxamate ligand, suggested that the three hydroxamate groups in DFO-D1 coordinate to Fe(III) surface sites relatively independently. The results also demonstrated a significant depleting effect of 240 {micro}M DFO-B or DFO-D1 on Pb(II) adsorption by goethite at pH {gt} 6.5, but there was no effect of adsorbed Pb(II) on the goethite dissolution rate.

  15. Gram-positive siderophore-shuttle with iron-exchange from Fe-siderophore to apo-siderophore by Bacillus cereus YxeB.

    PubMed

    Fukushima, Tatsuya; Allred, Benjamin E; Sia, Allyson K; Nichiporuk, Rita; Andersen, Ulla N; Raymond, Kenneth N

    2013-08-20

    Small molecule iron-chelators, siderophores, are very important in facilitating the acquisition of Fe(III), an essential element for pathogenic bacteria. Many Gram-negative outer-membrane transporters and Gram-positive lipoprotein siderophore-binding proteins have been characterized, and the binding ability of outer-membrane transporters and siderophore-binding proteins for Fe-siderophores has been determined. However, there is little information regarding the binding ability of these proteins for apo-siderophores, the iron-free chelators. Here we report that Bacillus cereus YxeB facilitates iron-exchange from Fe-siderophore to apo-siderophore bound to the protein, the first Gram-positive siderophore-shuttle system. YxeB binds ferrioxamine B (FO, Fe-siderophore)/desferrioxamine B (DFO, apo-siderophore) in vitro. Disc-diffusion assays and growth assays using the yxeB mutant reveal that YxeB is responsible for importing the FO. Cr-DFO (a FO analog) is bound by YxeB in vitro and B. cereus imports or binds Cr-DFO in vivo. In vivo uptake assays using Cr-DFO and FO and growth assays using DFO and Cr-DFO show that B. cereus selectively imports and uses FO when DFO is present. Moreover, in vitro competition assays using Cr-DFO and FO clearly demonstrate that YxeB binds only FO, not Cr-DFO, when DFO is bound to the protein. Iron-exchange from FO to DFO bound to YxeB must occur when DFO is initially bound by YxeB. Because the metal exchange rate is generally first order in replacement ligand concentration, protein binding of the apo-siderophore acts to dramatically enhance the iron exchange rate, a key component of the Gram-positive siderophore-shuttle mechanism.

  16. An Uninformative Truth: The Logic of Amarin's Off-Label Promotion.

    PubMed

    Hey, Spencer Phillips; Kesselheim, Aaron S

    2016-03-01

    Spencer Phillips Hey and Aaron Kesselheim propose that informativeness-asserting scientific facts-rather than truthfulness ought to be the standard for regulating commercial speech about pharmaceuticals.

  17. 77 FR 72335 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... Logistics Agency, DLA Information Operations Richmond, ATTN: Mr. Walter B. Gooch, 8000 Jefferson Davis..., workload calculation, or reporting purposes. Dated: November 30, 2012. Aaron Siegel, Alternate OSD...

  18. 78 FR 75334 - Meeting of the National Commission on the Structure of the Air Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    .... FOR FURTHER INFORMATION CONTACT: Mrs. Marcia Moore, Designated Federal Officer, National Commission on... Mrs. Marcia Moore, DFO, via facsimile or electronic mail, the preferred modes of submission. Each...

  19. Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

    PubMed Central

    Kang, Hui; Yan, Yufei; Jia, Peng; Yang, Kai; Guo, Changjun; Chen, Hao; Qi, Jin; Qian, Niandong; Xu, Xing; Wang, Fei; Li, Changwei; Guo, Lei; Deng, Lianfu

    2016-01-01

    As wear particles-induced osteolysis still remains the leading cause of early implant loosening in endoprosthetic surgery, and promotion of osteoclastogenesis by wear particles has been confirmed to be responsible for osteolysis. Therapeutic agents targeting osteoclasts formation are considered for the treatment of wear particles-induced osteolysis. In the present study, we demonstrated for the first time that desferrioxamine (DFO), a powerful iron chelator, could significantly alleviate osteolysis in an ultrahigh-molecular-weight polyethylene (UHMWPE) particles-induced mice calvaria osteolysis model. Furthermore, DFO attenuated calvaria osteolysis by restraining enhanced inflammatory osteoclastogenesis induced by UHMWPE particles. Consistent with the in vivo results, we found DFO was also able to inhibit osteoclastogenesis in a dose-dependent manner in vitro, as evidenced by reduction of osteoclasts formation and suppression of osteoclast specific genes expression. In addition, DFO dampened osteoclasts differentiation and formation at early stage but not at late stage. Mechanistically, the reduction of osteoclastogenesis by DFO was due to increased heme oxygenase-1 (HO-1) expression, as decreased osteoclasts formation induced by DFO was significantly restored after HO-1 was silenced by siRNA, while HO-1 agonist COPP treatment enhanced DFO-induced osteoclastogenesis inhibition. In addition, blocking of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway promoted DFO-induced HO-1 expression, implicating that p38 signaling pathway was involved in DFO-mediated HO-1 expression. Taken together, our results suggested that DFO inhibited UHMWPE particles-induced osteolysis by restraining inflammatory osteoclastogenesis through upregulation of HO-1 via p38MAPK pathway. Thus, DFO might be used as an innovative and safe therapeutic alternative for treating wear particles-induced aseptic loosening. PMID:27787522

  20. A spectroscopic study of the effects of a microbial siderophore on Pb adsorption to kaolinite

    SciTech Connect

    Mishra, Bhoopesh; Haack, Elizabeth A.; Maurice, Patricia A.; Bunker, Bruce A.

    2010-11-12

    Batch adsorption experiments were combined with X-ray Absorption Spectroscopy (XAS) analysis to determine the mechanism(s) whereby the microbial trihydroxamate siderophore ligand desferrioxamine-B (DFO-B) affects Pb sorption to kaolinite at pH 4, 6, and 7.5 (in 0.1 M NaClO{sub 4}, 22 C; Pb:DFO-B ratio 120:240 {micro}M). In the absence of DFO-B, Pb adsorbs only slightly to kaolinite at pH 4, by a combination of inner- and outer-sphere complexation. Adsorption increases at pH 6, and sorption (adsorption/surface precipitation) further increases at pH 7.5. At pH 4, DFO-B does not bind Pb in solution appreciably, and the Pb adsorption mechanism(s) is unchanged by the presence of DFO-B. At pH 6, DFO-B slightly enhances Pb adsorption, due at least in part to formation of a DFO-B-Pb-kaolinite type A ternary surface complex. At pH 7.5, DFO-B decreases Pb sorption and Pb adsorption is dominated by a DFO-B-Pb-kaolinite type A ternary surface complex. Although XAS and thermodynamic speciation modeling indicate that Pb is bound by multiple DFO-B functional groups in solution at pH 7.5, the DFO-B-Pb-kaolinite surface complex appears to involve only a single hydroxamate group. This study thus demonstrates that the detailed structure of a ternary surface complex cannot necessarily be predicted from the structure of the solution organic-metal complex.

  1. Cardiac and hepatic iron and ejection fraction in thalassemia major: Multicentre prospective comparison of combined Deferiprone and Deferoxamine therapy against Deferiprone or Deferoxamine Monotherapy

    PubMed Central

    2013-01-01

    Background Due to the limited data available in literature, the aim of this multi-centre study was to prospectively compare in thalassemia major (TM) patients the efficacy of combined deferiprone (DFP) and deferoxamine (DFO) regimen versus either DFP and DFO in monotherapy by cardiovascular magnetic resonance (CMR) over a follow up of 18 months. Methods Among the first 1135 TM patients in the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated those who had received either combined regimen (DFO + DFP, N=51) or DFP (N=39) and DFO (N=74) monotherapies between the two CMR scans. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results The percentage of patients that maintained a normal global heart T2* value was comparable between DFP+DFO versus both monotherapy groups. Among the patients with myocardial iron overload at baseline, the changes in the global heart T2* and in biventricular function were not significantly different in DFP+DFO compared with the DFP group. The improvement in the global heart T2* was significantly higher in the DFP+DFO than the DFO group, without a difference in biventricular function. Among the patients with hepatic iron at baseline, the decrease in liver iron concentration values was significantly higher with combination therapy than with either monotherapy group. Conclusions In TM patients at the dosages used in the real world, the combined DFP+DFO regimen was more effective in removing cardiac iron than DFO, and was superior in clearing hepatic iron than either DFO or DFP monotherapy. Combined therapy did not show an additional effect on heart function over DFP. PMID:23324167

  2. Mind, Machine, and Creativity: An Artist's Perspective

    ERIC Educational Resources Information Center

    Sundararajan, Louise

    2014-01-01

    Harold Cohen is a renowned painter who has developed a computer program, AARON, to create art. While AARON has been hailed as one of the most creative AI programs, Cohen consistently rejects the claims of machine creativity. Questioning the possibility for AI to model human creativity, Cohen suggests in so many words that the human mind takes a…

  3. The Dynamics of Equatorial F Layer Irregularities.

    DTIC Science & Technology

    2014-09-26

    RD-8158 650 THE DYNAMICS OF EQUATORIAL F LAYER IRREGULARITIE5(U) BOSTON UNIV MR DEPT OF ASTRONOMY J AARONS ET AL. 38 JUN 85 RCBU-6276-5 N88814-82-K...Jules Aarons and Michael Mendillo, Co-Principal Investigators Department of Astronomy Boston University Boston, MA 02215 BOSTON UNIVERSITY Thi doumnt

  4. The Vod Couple

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2009-01-01

    This article features two high school chemistry teachers, Aaron Sams and Jonathan Bergmann, who have overturned conventional classroom instruction by using video podcasts to form the root of a new learning model. Thumbing through an issue of "MacWorld" a few years ago, Aaron Sams was struck by an article about an application called ProfCast that…

  5. Measures of Effectiveness: Israeli Counterterrorism Strategies and Tactics During the Al-Aqsa Intifada

    DTIC Science & Technology

    2006-09-01

    intensify, and further radicalize, the resistance movement. 209 Aaron D. Pina , "Fatah and Hamas: The New...Raphael. "Combating Terrorism: The Challenge of Measuring Effectiveness" CRS Report for Congress 23 November 2005. Pina , Aaron D. "Fatah and

  6. 78 FR 26368 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... trusts: Aaron W. Anderson Trust; Angela Anderson Swift Trust; Emery Kent Fager Trust; John Fontron Fager Trust; Melissa Fager Hiestand Trust; Adam William Anderson Trust; Joshua Robert Anderson Trust; Sydney... 64198-0001: 1. Aaron W. Anderson, Topeka, Kansas; Angela Anderson Swift, Overland Park, Kansas;...

  7. 75 FR 61139 - Blue Ribbon Commission on America's Nuclear Future, Reactor and Fuel Cycle Technology Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-04

    ...: Department of Energy, Office of Nuclear Energy. ACTION: Notice of Open Meeting. SUMMARY: This notice... CommissionDFO@nuclear.energy.gov . Additional information will be available at http://www.brc.gov... Avenue, SW., Washington, DC 20585; e-mail to CommissionDFO@nuclear.energy.gov , or post comments on...

  8. 76 FR 4646 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ... Ribbon Commission on America's Nuclear Future AGENCY: Department of Energy, Office of Nuclear Energy... facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional information will be... to CommissionDFO@nuclear.energy.gov , or post comments on the Commission Web site at...

  9. 75 FR 43518 - Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... of Energy, Office of Nuclear Energy. ACTION: Notice of open meeting. SUMMARY: This notice announces..., DC 20585; telephone (202) 586-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy... Independence Avenue, SW., Washington DC 20585, e-mail to CommissionDFO@nuclear.energy.gov , or post comments...

  10. 75 FR 51025 - Blue Ribbon Commission on America's Nuclear Future, Reactor and Fuel Cycle Technology Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ...: Department of Energy, Office of Nuclear Energy. ACTION: Notice of open meeting. SUMMARY: This notice...- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional information will be available at http://www... to CommissionDFO@nuclear.energy.gov , or post comments on the Commission Web site at...

  11. 75 FR 25850 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-10

    ... Ribbon Commission on America's Nuclear Future AGENCY: Department of Energy, Office of Nuclear Energy...- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional information may also be available at http... to CommissionDFO@nuclear.energy.gov , or post comments on the Commission Web site at...

  12. 78 FR 34995 - Response Systems to Adult Sexual Assault Crimes Panel (Response Systems Panel); Notice of Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ..., Room 3B747, Washington, DC 2030122203. Email: ResponseSystemPanelDFO@osd.mil . Phone: (703) 571-2664... notice in the following formats: Adobe Acrobat, WordPerfect, or Microsoft Word. Please note that since...SystemPanelDFO@osd.mil . Phone: (703) 571- 2664. For meeting information please contact Ms. Fried....

  13. 76 FR 28224 - Cancellation of the Local Government Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-16

    ... later date. Further information regarding this meeting can be obtained by contacting Paula Zampieri, DFO for the Local Government Advisory Committee (LGAC) at (202) 566-2496 or Zampieri.Paula@epa.gov... or any future meetings should contact Ms. Paula Zampieri, Designated Federal Officer (DFO) for...

  14. 76 FR 41323 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... contact Susan Lender, Designated Federal Officer (DFO), (the Contact Person listed below) by phone or e... contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail) by August 4, 2011... special assistance should inform the Contact Person listed below in advance of the meeting. FOR...

  15. 77 FR 31847 - Notification of a Public Meeting and Public Teleconference of the Science Advisory Board (SAB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ... meeting or teleconference may contact Mr. Thomas Carpenter, Designated Federal Officer (DFO), via telephone at (202) 564-4885 or email at carpenter.thomas@epa.gov . General information concerning the SAB... oral statements at the face-to-face meeting should contact Mr. Thomas Carpenter, DFO, in...

  16. 77 FR 64335 - Notification of a Public Teleconference of the Science Advisory Board; Perchlorate Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... Mr. Thomas Carpenter, Designated Federal Officer (DFO), EPA Science Advisory Board (1400R), U.S... ] (202) 564-4885; fax (202) 565-2098; or email at carpenter.thomas@epa.gov . General information... December 5, 2012 meeting, interested parties should notify Mr. Thomas Carpenter, DFO, by email no...

  17. Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients.

    PubMed

    Maggio, Aurelio; Vitrano, Angela; Lucania, Gaetano; Capra, Marcello; Cuccia, Liana; Gagliardotto, Francesco; Pitrolo, Lorella; Prossomariti, Luciano; Filosa, Aldo; Caruso, Vincenzo; Gerardi, Calogera; Campisi, Saveria; Cianciulli, Paolo; Rizzo, Michele; D'Ascola, Giuseppe; Ciancio, Angela; Di Maggio, Rosario; Calvaruso, Giuseppina; Pantalone, Gaetano Restivo; Rigano, Paolo

    2012-07-01

    A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].

  18. Effects of zinc-desferrioxamine on Plasmodium falciparum in culture.

    PubMed Central

    Chevion, M; Chuang, L; Golenser, J

    1995-01-01

    The zinc-desferrioxamine (Zn-DFO) complex is considered to be more permeative into parasitized erythrocytes than is the metal-free DFO. The former may penetrate the cell and exchange its bound zinc for ferric ions, rendering the iron unavailable for vital parasite functions. The effects of these compounds on the in vitro development of Plasmodium falciparum are compared. The results indicate that Zn-DFO is superior to DFO, especially at concentrations below 20 microM, as shown by decreased levels of hypoxanthine incorporation, lower levels of parasitemia, and interference with the life cycle of the parasite. At low concentrations, DFO even enhanced parasite growth. Such an enhancement was not observed following exposure to Zn-DFO. Experiments in which the compounds were removed from the cultures indicated that parasites treated with Zn-DFO are less likely to recover at a later stage. Since DFO has already been used in humans for the treatment of malaria, its complex with zinc, which is more effective in vitro, should also be examined in vivo. PMID:7486946

  19. Altered desferrioxamine-mediated iron utilization is a common trait of bald mutants of Streptomyces coelicolor.

    PubMed

    Lambert, Stéphany; Traxler, Matthew F; Craig, Matthias; Maciejewska, Marta; Ongena, Marc; van Wezel, Gilles P; Kolter, Roberto; Rigali, Sébastien

    2014-08-01

    Streptomyces coelicolor is an important model organism for developmental studies of filamentous GC-rich actinobacteria. The genetic characterization of mutants of S. coelicolor blocked at the vegetative mycelium stage, the so-called bald (bld) mutants that are unable to erect spore-forming aerial hyphae, has opened the way to discovering the molecular basis of development in actinomycetes. Desferrioxamine (DFO) production and import of ferrioxamines (FO; iron-complexed DFO) are key to triggering morphogenesis of S. coelicolor and we show here that growth of S. coelicolor on the reference medium for Streptomyces developmental studies is fully dependent on DFO biosynthesis. UPLC-ESI-MS analysis revealed that all bld mutants tested are affected in DFO biosynthesis, with bldA, bldJ, and ptsH mutants severely impaired in DFO production, while bldF, bldK, crr and ptsI mutants overproduce DFO. Morphogenesis of bldK and bldJ mutants was recovered by supplying exogenous iron. Transcript analysis showed that the bldJ mutant is impaired in expression of genes involved in the uptake of FO, whereas transcription of genes involved in both DFO biosynthesis and FO uptake is increased in bldK mutants. Our study allows proposing altered DFO production and/or FO uptake as a novel phenotypic marker of many S. coelicolor bld mutants, and strengthens the role of siderophores and iron acquisition in morphological development of actinomycetes.

  20. Synthesis, metal coordination, and cellular internalization of a siderophore-bearing NIR fluorescent carbocyanine probe

    NASA Astrophysics Data System (ADS)

    Ye, Yunpeng; Xu, Baogang; Bloch, Sharon; Achilefu, Samuel

    2006-02-01

    In order to explore novel NIR fluorescent probes for optical imaging in biomedicines, one desferrioxamine (DFO)-bearing NIR fluorescent probe was designed and synthesized based on a dicarboxylic acid-containing carbocyanine (Cypate). Similar to the free DFO, the resulting conjugate Cypate-DFO showed high binding affinity with Fe(III) and Ga(III) as identified by ES-MS. Nevertheless, the iron binding was found to quench its fluorescent emission significantly, suggesting that the siderophore moiety might perturb the spectroscopic properties of the attached carbocyanine fluorophore through metal binding. As observed by fluorescence microscopy, Cypate-DFO showed significant cellular internalization in A549 cells in vitro. Further studies on novel Cypate-DFO derivatives of this type may reveal some exciting properties and biological activities.

  1. Statement of Aaron Cohen, Director, Research and Engineering, Johnson Space Center and Chairman, Space Station Advanced Technology Advisory Committee, National Aeronautics and Space Administration, before the Subcommittee on Science, Technology, and Space, Committee on Commerce, Science, and Transportation, United States Senate

    NASA Technical Reports Server (NTRS)

    Cohen, A.

    1985-01-01

    The activities of NASA's Space Station Advanced Technology Advisory Committee is discussed. Advanced Technology Advisory Committee (ATAC) activities over the last year are reviewed in preparation of the report to Congress on the potential for advancing automation and robotics technology for the space station and for the U.S. economy.

  2. A novel bifunctional metabolizable linker for the conjugation of antibodies with radionuclides

    SciTech Connect

    Arano, Y.; Matsushima, H.; Tagawa, M.; Koizumi, M.; Endo, K.; Konishi, J.; Yokoyama, A. )

    1991-03-01

    A novel heterogeneous bifunctional reagent containing an ester bond, N-((4-(2-maleimidoethoxy)-succinyl)oxy)succinimide (MESS), was designed and synthesized for the conjugation of antibodies with the gallium-67 (67Ga) chelate of succinyldeferoxamine (SDF) via the ester bond. MESS was synthesized by the acylation of N-(2-hydroxyethyl)maleimide with succinic anhydride, followed by the activation of the resulting carboxylic acid to a succinimido ester. MESS possesses a maleimide group for protein conjugation and an active ester group for deferoxamine (DFO) coupling, and the two functional groups are linked via ester bonding. Conjugation of 67Ga-SDF with nonspecific human IgG was performed by reacting freshly thiolated IgG with the reaction product of MESS and DFO, followed by 67Ga labeling of the resulting conjugate using GaCl3 (67Ga-DFO-MESS-IgG). For comparison, 67Ga-DFO conjugated nonspecific human IgG with a nonmetabolizable linkage was synthesized under the same conjugation conditions as those for 67Ga-DFO-MESS-IgG, using a nonmetabolizable heterogenous bifunctional reagent (N-((6-maleimidocaproyl)oxy)succinimide, EMCS) instead of MESS (67Ga-DFO-EMCS-IgG). HPLC size-exclusion chromatography of both preparations showed a single radioactivity and UV peak corresponding to the intact IgG. Generation of 67Ga-SDF from the 67Ga-DFO-MESS-IgG was demonstrated by reverse-phase HPLC analysis and cellulose acetate electrophoresis after the incubation of 67Ga-DFO-MESS-IgG in a buffered solution containing carboxyesterase. After injection of 67Ga-DFO-MESS-IgG into mice, faster radioactivity clearance from the blood and less radioactivity accumulation in the liver, kidney, and spleen was noted than when 67Ga-DFO-EMCS-IgG was injected.

  3. Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration.

    PubMed

    Yao, Qingqing; Liu, Yangxi; Tao, Jianning; Baumgarten, Keith M; Sun, Hongli

    2016-11-30

    Utilizing biomimetic materials to potentiate endogenous cell growth or signaling is superior to relying on exogenous cells or signals for bone formation. Desferoxamine (DFO), which is a hypoxia-mimetic agent that chelates iron (Fe(3+)), mimics hypoxia to encourage bone healing. However, high cytotoxicity, off-target effects, and the short half-life of DFO have significantly impeded its further applications. We mitigated these side effects by locally immobilizing DFO onto a gelatin nanofibrous (GF) scaffold that retained DFO's ability to chelate Fe(3+). Moreover, DFO-functionalized GF (GF-DFO) scaffolds, which have similar micro/macrostructures to GF scaffolds, not only demonstrated decreased cytotoxicity on both human umbilical vein endothelial cells and human mesenchymal stem cells but also significantly increased vascular endothelial growth factor (VEGF) expression in vitro. Most importantly, in our in vivo experiments on a critical-sized cranial bone defect mouse model, a significant amount of bone was formed in most of the GF-DFO scaffolds after six weeks, while very little new bone was observed in the GF scaffolds. These data suggest that use of a hypoxia-mimicking nanofibrous scaffold is a promising strategy for promoting endogenous bone formation.

  4. Quantum chemical study of the Fe(III)-desferrioxamine B siderophore complex—Electronic structure, vibrational frequencies, and equilibrium Fe-isotope fractionation

    NASA Astrophysics Data System (ADS)

    Domagal-Goldman, S. D.; Paul, K. W.; Sparks, D. L.; Kubicki, J. D.

    2009-01-01

    This study presents molecular orbital/density functional theory (MO/DFT) calculations of the electronic structure, vibrational frequencies, and equilibrium isotope fractionation factors for iron desferrioxamine B (Fe-DFO-B) complexes in aqueous solution. In general, there was good agreement between the predicted properties of Fe(III)-DFO-B and previously published experimental and theoretical results. The predicted fractionation factor for equilibrium between Fe(III)-DFO-B and Fe(III)-catecholate at 22 °C, 0.68 ± 0.25‰, was in good agreement with a previously measured isotopic difference between bacterial cells and solution during the bacterial-mediated dissolution of hornblende [Brantley S. L., Liermann L. and Bullen T. D. (2001) Fractionation of Fe isotopes by soil microbes and organic acids. Geology29, 535-538]. Conceptually, this agreement is consistent with the notion that Fe is first removed from mineral surfaces via complexation with small organic acids (e.g., oxalate), subsequently sequestered by DFO-B in solution, and ultimately delivered to bacterial cells by Fe(III)-DFO-B complexes. The ability of DFO-B to discriminate between Fe(III) and Fe(II)/Al(III) was investigated with Natural Bond Orbital (NBO) analysis and geometry calculations of each metal-DFO-B complex. The results indicated that higher affinity for Fe(III) is not strictly a function of bond length but also the degree of Fe-O covalent bonding.

  5. Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate.

    PubMed

    Rassu, Giovanna; Soddu, Elena; Cossu, Massimo; Brundu, Antonio; Cerri, Guido; Marchetti, Nicola; Ferraro, Luca; Regan, Raymond F; Giunchedi, Paolo; Gavini, Elisabetta; Dalpiaz, Alessandro

    2015-03-10

    We propose the formulation and characterization of solid microparticles as nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial-like). Nasal administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) to 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after nasal administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.

  6. Direct evidence of iron uptake by the Gram-positive siderophore-shuttle mechanism without iron reduction.

    PubMed

    Fukushima, Tatsuya; Allred, Benjamin E; Raymond, Kenneth N

    2014-09-19

    Iron is an essential element for all organisms, and microorganisms produce small molecule iron-chelators, siderophores, to efficiently acquire Fe(III). Gram-positive bacteria possess lipoprotein siderophore-binding proteins (SBPs) on the membrane. Some of the SBPs bind both apo-siderophores (iron-free) and Fe-siderophore (iron-chelated) and only import Fe-siderophores. When the SBP initially binds an apo-siderophore, the SBP uses the Gram-positive siderophore-shuttle mechanism (the SBPs exchange Fe(III) from a Fe-siderophore to the apo-siderophore bound to the protein) and/or displacement mechanism (the apo-siderophore bound to the SBP is released and a Fe-siderophore is then bound to the protein) to import the Fe-siderophore. Previously, we reported that the Bacillus cereus SBP, YxeB, exchanges Fe(III) from a ferrioxamine B (FO) to a desferrioxamine B (DFO) bound to YxeB using the siderophore-shuttle mechanism although the iron exchange was indirectly elucidated. Synthetic Cr-DFO (inert metal FO analog) and Ga-DFO (nonreducible FO analog) are bound to YxeB and imported via YxeB and the corresponding permeases and ATPase. YxeB exchanges Fe(III) from FO and Ga(III) from Ga-DFO to DFO bound to the protein, indicating that the metal-exchange occurs without metal reduction. YxeB also binds DFO derivatives including acetylated DFO (apo-siderophore) and acetylated FO (AcFO, Fe-siderophore). The iron from AcFO is transferred to DFO when bound to YxeB, giving direct evidence of iron exchange. Moreover, YxeB also uses the displacement mechanism when ferrichrome (Fch) is added to the DFO:YxeB complex. Uptake by the displacement mechanism is a minor pathway compared to the shuttle mechanism.

  7. 75 FR 36779 - Qualification of Drivers; Exemption Renewals; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    .... Schnautz, Steve J. Sherar, Robert F. Skinner, Jr., William T. Smiley, Richard M. Smith, Robert A. Stoeckle, David N. Stubbs, Edward J. Sullivan, Aaron S. Taylor, Martin L. Taylor, Gary R. Thomas, William...

  8. 77 FR 66182 - TRICARE Over-the-Counter Drug Demonstration Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-02

    ... demonstration project under 10 U.S.C. 1092 to allow certain over-the- counter (OTC) medications to be included... demonstration project continues to be authorized by 10 U.S.C. 1092. Dated: October 31, 2012. Aaron...

  9. Rfinity

    ScienceCinema

    Aaron R. Turner

    2016-07-12

    An innovation that offers a low-cost, plug-n-play option that enables virtually any wireless telecommunications device to safely store sensitive personal information and perform secure transactions. INL researchers include Steven McCown, Aaron Turner, Kur

  10. NASA Now: Exercise Physiology: Countermeasures

    NASA Video Gallery

    Aaron Weaver is a biomedical engineer responsible for setting up and running experiments and recruiting test subjects in the Exercise Countermeasures Laboratory at NASA’s Glenn Research Center in...

  11. NASA Now Minute: Exercise Physiology: Countermeasures

    NASA Video Gallery

    Aaron Weaver, a biomedical engineer, discusses the importance of doingexercise while in space and provides a glimpse into one of NASA’slaboratories developing and improving the exercise equipme...

  12. Theories of suicidal behavior applied to Sylvia Plath.

    PubMed

    Lester, D

    1998-01-01

    The suicide of Sylvia Plath is examined from the perspective of 15 theories of suicidal behavior and is found to fit best with psychoanalytic and cognitive theories of suicide, in particular those of Aaron Beck, Henry Murray, and Edwin Shneidman.

  13. 76 FR 61346 - Senior Executive Service Performance Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... Business Administration Elizabeth Martin General Counsel, United States Postal Service Mary Mitchelson Deputy Inspector General, Department of Education Daniel J. O'Rourke Assistant Inspector General for..., Department of Education Dated: September 28, 2011. Aaron Siegel, Alternate OSD Federal Register...

  14. 78 FR 63970 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... interventions. The information collection will be maintained electronically and solely within the local area network of the USAPHC and AIPH. Dated: October 21, 2013. Aaron Siegel, Alternate OSD Federal...

  15. Views of the Apollo 11 Twentieth Anniversary Black Tie reception

    NASA Technical Reports Server (NTRS)

    1989-01-01

    View from the Apollo 11 Twentieth Anniversary Black Tie reception at the downtown Houston Hyatt Regency Hotel. Scene show NASA/JSC Director Aaron Cohen talking with NASA Administrator Richard H. Truly and his wife, Cody.

  16. 75 FR 30405 - Change in Bank Control Notices; Acquisition of Shares of Bank or Bank Holding Companies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ...) 90 Hennepin Avenue, Minneapolis, Minnesota 55480-0291: 1. Aaron Matthew Ness, Michael Forrest Ness... Hunter Ness Roth IRA, all of Yankton, South Dakota; Michael Forrest Ness, Sioux Falls, South...

  17. 77 FR 51532 - Environmental Impacts Statements; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ..., CA, Review Period Ends: 09/24/2012, Contact: Aaron Burton 909-388-2841. EIS No. 20120270, Final..., Comment Period Ends: 10/08/2012, Contact: Richard Kehr 406-837-7500. Amended Notices EIS No....

  18. Staff Development in Reading: What the Experts Say.

    ERIC Educational Resources Information Center

    Vacca, Jo Anne

    1979-01-01

    Presents interviews of six prominent researchers (Ira Aaron, Harold Herber, Wayne Otto, Robert Ruddell, Roselmina Indrisano, and Olive Niles), which focused on the dynamics constituting effective staff development experiences. (HOD)

  19. Rfinity

    SciTech Connect

    Aaron R. Turner

    2009-07-21

    An innovation that offers a low-cost, plug-n-play option that enables virtually any wireless telecommunications device to safely store sensitive personal information and perform secure transactions. INL researchers include Steven McCown, Aaron Turner, Kur

  20. Russell Sage: Private Research for the Public Good

    ERIC Educational Resources Information Center

    Kaplan, Carl S.

    1977-01-01

    The development of the Russell Sage Foundation, devoted to social science research, is reviewed with emphasis on its outlook under the new president, Aaron Wildavsky, and his expertise in policy analysis. (LBH)

  1. Kennedy Space Center Wakes STS-135 Crew

    NASA Video Gallery

    The Flight Day 13 wakeup music was "Fanfare for the Common Man" by Aaron Copland played for Commander Chris Ferguson. It was followed by a prerecorded message from Kennedy Space Center employees. K...

  2. 78 FR 34994 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ... provided by the military member. A medical doctor or psychiatrist, college administrator, or a dependent's..., waste, and abuse of dependent benefits. Dated: June 4, 2013. Aaron Siegel, Alternate OSD...

  3. 75 FR 80048 - Science Advisory Board Staff Office; Notification of a Public Meeting of the Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

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  4. 78 FR 64941 - Government-Wide Travel Advisory Committee (GTAC); Public Advisory Committee Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

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  5. 76 FR 24486 - Next Meeting of the North American Numbering Council

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  6. 75 FR 13595 - Workforce Investment Act; Native American Employment and Training Council

    Federal Register 2010, 2011, 2012, 2013, 2014

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  7. 77 FR 22003 - Workforce Investment Act; Native American Employment and Training Council

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  8. 76 FR 64126 - Advisory Committee on Reactor Safeguards; Procedures for Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... allotted to present oral statements can be obtained by contacting the DFO. (d) The use of still, motion picture, and television cameras will be permitted at the discretion of the Chairman and subject to...

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    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

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  10. 78 FR 73189 - Next Meeting of the North American Numbering Council

    Federal Register 2010, 2011, 2012, 2013, 2014

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    ... Collection (NANP B&C) Agent 7. Report of the Billing and Collection Working Group (B&C WG) 8. Report of the... with the approval of the DFO. Federal Communications Commission. Sanford S. Williams,...

  11. 78 FR 50404 - Advanced Scientific Computing Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... sufficient access lines for the public, we request that members of the public notify the DFO, Christine Chalk that you intend to call-into the meeting via email at: christine.chalk@science.doe.gov . FOR...

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Federal Register 2010, 2011, 2012, 2013, 2014

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  14. 75 FR 44818 - Advisory Committee on Reactor Safeguards (ACRS): Meeting of the ACRS Subcommittee on Plant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-29

    ... should notify the Designated Federal Official (DFO), Girija Shukla (Telephone 301-415-6855 or E-mail Girija.Shukla@nrc.gov ) five days prior to the meeting, if possible, so that appropriate arrangements...

  15. Sickle cell anemia: the impact of discovery, politics, and business.

    PubMed

    Xie, Lai-Hua; Doye, Angelia A; Conley, Eric; Gwathmey, Judith K

    2013-11-01

    Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that our novel formulation lowered the dosage requirements by 50%-75%, allowed for less frequent and shorter treatment durations, eliminating the need for a pump and the standard multi-night administration of DFO. In an iron-overloaded rat model, LDFO reduced iron in the liver, and also improved cardiac function. The lower dosage and improved safety profile makes our novel LDFO delivery system a highly desirable new therapy. Meanwhile, this system will also provide an ideal model for studying the mechanism of Fe overload-induced arrhythmias. The political and economic factors related to health care disparities are also discussed.

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    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

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    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    ... comments should notify the Designated Federal Official (DFO), John Lai (Telephone 301-415-5197 or Email: John.Lai@nrc.gov ) five days prior to the meeting, if possible, so that appropriate arrangements can...

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    ... oral statements and/or written comments should notify the Designated Federal Official (DFO), John Lai (Telephone 301-415-5197 or Email: John.Lai@nrc.gov ) five days prior to the meeting, if possible, so...

  1. Complexation of Pu(IV) with the natural siderophore desferrioxamine B and the redox properties of Pu(IV)(siderophore) complexes.

    PubMed

    Boukhalfa, Hakim; Reilly, Sean D; Neu, Mary P

    2007-02-05

    The bioavailability and mobility of Pu species can be profoundly affected by siderophores and other oxygen-rich organic ligands. Pu(IV)(siderophore) complexes are generally soluble and may constitute with other soluble organo-Pu(IV) complexes the main fraction of soluble Pu(IV) in the environment. In order to understand the impact of siderophores on the behavior of Pu species, it is important to characterize the formation and redox behavior of Pu(siderophore) complexes. In this work, desferrioxamine B (DFO-B) was investigated for its capacity to bind Pu(IV) as a model siderophore and the properties of the complexes formed were characterized by optical spectroscopy measurements. In a 1:1 Pu(IV)/DFO-B ratio, the complexes Pu(IV)(H2DFO-B)4+, Pu(IV)(H1DFO-B)3+, Pu(IV)(DFO-B)2+, and Pu(IV)(DFO-B)(OH)+ form with corresponding thermodynamic stability constants log beta1,1,2 = 35.48, log beta1,1,1 = 34.87, log beta1,1,0 = 33.98, and log beta1,1,-1 = 27.33, respectively. In the presence of excess DFO-B, the complex Pu(IV)H2(DFO-B)22+ forms with the formation constant log beta2,1,2 = 62.30. The redox potential of the complex Pu(IV)H2(DFO-B)22+ was determined by cyclic voltammetry to be E1/2 = -0.509 V, and the redox potential of the complex Pu(IV)(DFO-B)2+ was estimated to be E1/2 = -0.269 V. The redox properties of Pu(IV)(DFO-B)2+ complexes indicate that Pu(III)(siderophore) complexes are more than 20 orders of magnitude less stable than their Pu(IV) analogues. This indicates that under reducing conditions, stable Pu(siderophore) complexes are unlikely to persist.

  2. High-Temperature Transitions in Metallopolymers Crosslinked With 2,6-bis(1’-methylbenzimidazolyl)pyridine Metal-Ligand Complex

    DTIC Science & Technology

    2013-10-01

    C . Jackson, Robert H . Lambeth, Victor Rodriguez-Santiago, Brady G. Butler, and Frederick L. Beyer ARL-TR-6706 October 2013...Temperature Transitions in Metallopolymers Crosslinked With 2,6-bis(1’-methylbenzimidazolyl)pyridine Metal-Ligand Complex Aaron C . Jackson, Robert H ...5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Aaron C . Jackson, Robert H . Lambeth, Victor Rodriguez-Santiago

  3. Development of Parallel GSSHA

    DTIC Science & Technology

    2013-09-01

    C en te r Paul R. Eller , Jing-Ru C. Cheng, Aaron R. Byrd, Charles W. Downer, and Nawa Pradhan September 2013 Approved for public release...Program ERDC TR-13-8 September 2013 Development of Parallel GSSHA Paul R. Eller and Jing-Ru C. Cheng Information Technology Laboratory US Army Engineer...5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Paul Eller , Ruth Cheng, Aaron Byrd, Chuck Downer, and Nawa Pradhan 5d. PROJECT NUMBER

  4. An Approximate Dynamic Programming Mode for Optimal MEDEVAC Dispatching

    DTIC Science & Technology

    2015-03-26

    An Approximate Dynamic Programming Model For MEDEVAC Dispatching THESIS MARCH 2015 Aaron J. Rettke, Captain, USA AFIT-ENS-MS-15-M-115 DEPARTMENT OF...and is not subject to copyright protection in the United States. AFIT-ENS-MS-15-M-115 AN APPROXIMATE DYNAMIC PROGRAMMING MODEL FOR MEDEVAC... APPROXIMATE DYNAMIC PROGRAMMING MODEL FOR MEDEVAC DISPATCHING THESIS Aaron J. Rettke, BS, MS Captain, USA Committee Membership: Lt Col Matthew J

  5. Results of SEI Independent Research and Development Projects and Report on Emerging Technologies and Technology Trends

    DTIC Science & Technology

    2005-12-01

    W. Collins Peter Feiler John Goodenough Aaron Greenhouse Jorgen Hansson Alan R. Hevner John Hudak Angel Jordan Rick Kazman Richard C . Linger...Mark G. Pleszkoch Stacy J. Prowell Natasha Sharygina Kurt C . Wallnau Gwen Walton Chuck Weinstock Lutz Wrage December 2005...John Goodenough Aaron Greenhouse Jorgen Hansson Alan R. Hevner John Hudak Angel Jordan Rick Kazman Richard C . Linger Mark G. Pleszkoch Stacy J

  6. Exoskeleton Enhancements for Marines: Tactical-level Technology for an Operational Consequence

    DTIC Science & Technology

    2010-01-01

    Marine Corps Gazette, Quantico, VA: September 2005, 76-79. Dollar, Aaron M. & Herr, Hugh. “Lower Extremity Exoskeletons and Active Orthoses ...Challenges and State-of-the-Art” (IEEE Transactions on Robotics, VOL. 24, NO. 1, February 2008) Herr, Hugh. “Commentary Exoskeletons and Orthoses ...Aaron M. Dollar & Hugh Herr Lower Extremity Exoskeletons and Active Orthoses : Challenges and State-of-the-Art (IEEE TRANSACTIONS ON ROBOTICS, VOL. 24

  7. A Prototype Cesium Clock Ensemble for The Loran-C Radionavigation System

    DTIC Science & Technology

    2008-12-01

    40th Annual Precise Time and Time Interval (PTTI) Meeting A PROTOTYPE CESIUM CLOCK ENSEMBLE FOR THE LORAN -C RADIONAVIGATION SYSTEM...LTjg. Aaron P. Dahlen United States Coast Guard Loran Support Unit 12001 Pacific Ave Wildwood, NJ 08260-3232, USA Tel: 609-523-7204; Fax: 609-523...7320 E -mail: Aaron.P.Dahlen@uscg.mil Abstract This paper presents a prototype real time clock ensemble designed for semi-autonomous

  8. A Model of Onion Routing With Provable Anonymity

    DTIC Science & Technology

    2006-08-30

    Yale University Department of Computer Science A Model of Onion Routing with Provable Anonymity Aaron Johnson YALEU/DCS/TR-1368 August 30, 2006...2006 2. REPORT TYPE 3. DATES COVERED 00-08-2006 to 00-08-2006 4. TITLE AND SUBTITLE A Model of Onion Routing with Provable Anonymity 5a... Anonymity Aaron Johnson∗ Department of Computer Science Yale University New Haven, CT ajohnson@cs.yale.edu Abstract Onion routing is a scheme for anonymous

  9. More Anonymous Onion Routing Through Trust

    DTIC Science & Technology

    2009-07-01

    attempt to compromise his anonymity . How should he take this trust into account when he selects his paths? 2.1. The model To make this question concrete...It also does not take into account the total effect of an adversary’s actions on a user’s anonymity , such as the analysis performed in [24]. The...More Anonymous Onion Routing Through Trust Aaron Johnson Computer Science Department Yale University New Haven, CT 06520 USA aaron.johnson@yale.edu

  10. LIRA: Lightweight Incentivized Routing for Anonymity

    DTIC Science & Technology

    2013-02-01

    accountability that plagues PAR and XPAY, wherein anonymity inherently de- creases as the ability to detect cheaters improves. Ngan et al. propose a...LIRA: Lightweight Incentivized Routing for Anonymity Rob Jansen Aaron Johnson U.S. Naval Research Laboratory {rob.g.jansen, aaron.m.johnson...prob- lems stemming from a lack of incentives for volunteers to contribute. Insufficient capacity limits scalability and harms the anonymity of its

  11. MSR 2.0: Language Definition and Programming Environment

    DTIC Science & Technology

    2011-11-01

    15, pages 175–190, Cape Breton , NS, Canada, 2002. IEEE Computer Society Press. [3] Frederic Butler, Iliano Cervesato, Aaron D. Jaggard, and Andre ...Bibliography [1] Michael Backes, Iliano Cervesato, Aaron D. Jaggard, Andre Scedrov, and Joe-Kai Tsay. Cryptographi- cally Sound Security Proofs for...Jaggard, and Andre Scedrov. A Formal Analysis of Some Properties of Kerberos 5 Using MSR. In Fifteenth Computer Security Foundations Workshop — CSFW

  12. A Study on the Effect of Voluntary Retirement of Captains with Prior Service on Field Grade Officer Shortfalls in Critically Manned Mission Support Career Fields

    DTIC Science & Technology

    1989-05-01

    SHORTFALLS IN CRITICALLY (V) MANNED MISSION SUPPORT CAREER FIELDS N*. I LT COL DAVID P. CSINTYAN LT COL CHARLES K . LEONARD LT COL AARON B. ROGERS, JR...FIELDS by David P. Csintyan, Lt Col, USAF Charles K . Leonard, Lt Col, USAF Aaron B. Rogers, Jr., Lt Col, USAF A DEFENSE ANALYTICAL STUDY SUBMITTED TO...Officers School in 1975, Naval Command and Staff College in 1984, and Air War College in 1989. v BIOGRAPHICAL SKETCH Lieutenant Colonel Charles K

  13. Employing the Management Internal Control Toolset (MICT) Across the Enterprise

    DTIC Science & Technology

    2012-06-16

    Aaron Carta . While no longer with the MICT development team, he literally took the software and associated capabilities from concept to reality...a. This has been outstanding over the past several years as the MICT programmers led by Mr. Aaron Carta have evolved the software to meet new...due to the interaction between the inspection cycles, MICT performance would look worse than it actually is, because it followed the previous

  14. [Orthodontic treatment in children suffering from obstructive sleep apnea].

    PubMed

    Huet, A P; Paulus, C

    2015-09-01

    The obstructive sleep apnea syndrome (OSAS) may affect children, especially those with dentofacial disharmonies. Dentofacial orthopedic (DFO) treatments carried out in those patients must take this condition into account and can, in selected cases, improve or even treat the OSAS. The goal of our work was to report our experience about DFO treatments of children affected by OSAS in the department of maxillofacial surgery of Femme-Mère-Enfant hospital of university hospitals of Lyon, France.

  15. Bacterial siderophores promote dissolution of UO2 under reducing conditions.

    PubMed

    Frazier, Scott W; Kretzschmar, Ruben; Kraemer, Stephan M

    2005-08-01

    Tetravalent actinides are often considered environmentally immobile due to their strong hydrolysis and formation of sparingly soluble oxide phases. However, biogenic ligands commonly found in the soil environment may increase their solubility and mobility. We studied the adsorption and dissolution kinetics of UO2 in the presence of a microbial siderophore, desferrioxamine-B (DFO-B), under reducing conditions. Using batch and continuous flow stirred tank reactors (CFSTR),we found that DFO-B increases the solubility of UIV and accelerates UO2 dissolution rates through a ligand-promoted dissolution mechanism. DFO-B adsorption to UO2 followed a Langmuir-type isotherm. The maximum adsorbed DFO-B concentrations were 3.3 micromol m(-2) between pH 3 and 8 and declined above pH 8. DFO-B dissolved UO2 at a DFO-B surface-saturated net rate of 64 nmol h(-1) m(-2) (pH 7.5, l = 0.01 M) according to the first-order rate equation R = kL[Lads], with a rate coefficient kL of 0.019 h(-1). Even at very low siderophore concentrations (e.g. 1 microM), net dissolution rates (16 nmol h(-1) m(-2), pH 7.5, l = 0.01 M) were substantially greater than net proton-promoted dissolution rates (3 nmol h(-1) m(-2), pH 7-7.5, l = 0.01 M). Interestingly, adding dissolved FeIII had negligible effects on DFO-B-promoted UO2 dissolution rates, despite its potential as a competitor for DFO-B and as an oxidant of UIV. Our results suggest that strong organic ligands could influence the environmental mobility of tetravalent actinides and should be considered in predictions for nuclear waste storage and remediation strategies.

  16. XAFS Determination of Pb and Cd Speciation with Siderophores and the Metal/Siderophore/Kaolinite System

    NASA Astrophysics Data System (ADS)

    Mishra, Bhoopesh; Haack, Elizabeth A.; Vasconcelos, Igor F.; Maurice, Patricia A.; Bunker, Bruce A.

    2007-02-01

    We provide evidence for hexadentate complexes of Pb2+ and Cd2+ with the trihydroxamate siderophore desferrioxamine B (DFO-B) at pH 7.5, and 9.0, respectively. Analysis of the species of Pb2+ and Cd2+ adsorbed at the surface of kaolinite clay under the same pH conditions and in the presence of DFO-B indicate that Pb2+ is sorbed as a metal-siderophore complex while Cd2+ is not.

  17. XAFS Determination of Pb and Cd Speciation with Siderophores and the Metal/Siderophore/Kaolinite System

    SciTech Connect

    Mishra, Bhoopesh; Vasconcelos, Igor F.; Bunker, Bruce A.; Haack, Elizabeth A.; Maurice, Patricia A.

    2007-02-02

    We provide evidence for hexadentate complexes of Pb2+ and Cd2+ with the trihydroxamate siderophore desferrioxamine B (DFO-B) at pH 7.5, and 9.0, respectively. Analysis of the species of Pb2+ and Cd2+ adsorbed at the surface of kaolinite clay under the same pH conditions and in the presence of DFO-B indicate that Pb2+ is sorbed as a metal-siderophore complex while Cd2+ is not.

  18. A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia.

    PubMed

    Kuo, Kevin H M; Mrkobrada, Marko

    2014-01-01

    β-Thalassemia major (β-TM) patients require life-long blood transfusions, resulting in iron overload with multi-organ morbidity and mortality. Evidence from small randomized controlled trials (RCTs) published to date for deferiprone (DFP) monotherapy or in combination with deferoxamine (DFO) is unclear. We summarized evidence on the efficacy of DFP monotherapy compared to DFO, and DFP-DFO combination therapy compared to DFP or DFO monotherapy in chronically transfused β-TM. We searched four electronic databases and examined the grey literature. Two authors independently assessed trial quality and extracted data. We calculated the relative risk for dichotomous outcomes and mean difference (MD) for continuous outcomes. We identified 15 RCTs (1003 participants) that met the inclusion criteria. Deferiprone was more efficacious than DFO in improving cardiac ejection fraction [MD 2.88, 95% CI (95% confidence interval) 1.12 to 4.64, p = 0.001) and endocrine dysfunction (MD 0.09, 95% CI 0.08 to 0.10, p < 0.00001). The DFP-DFO combination therapy was more efficacious than DFP or DFO monotherapy in improving cardiac ejection fraction (MD 5.67, 95% CI 1.32 to 10.02, p = 0.008). There was no significant difference in all other outcomes examined. Meta-analysis on changes in myocardial iron content was not possible due to differences in data presentation. The quality of evidence for all outcomes was low. There is currently insufficient evidence to show that DFP is superior to DFO in the treatment of iron overload. The use of DFP must be weighed against the potential side-effects, patient compliance and preference. Large RCTs with clinically relevant outcomes are required.

  19. Optimization of desferrioxamine E production by Streptomyces parvulus.

    PubMed

    Gáll, Tamás; Lehoczki, Gábor; Gyémánt, Gyöngyi; Emri, Tamás; Szigeti, Zsuzsa M; Balla, György; Balla, József; Pócsi, István

    2016-12-01

    Siderophores are produced by a number of microbes to capture iron with outstandingly high affinity, which property also generates biomedical and industrial interests. Desferrioxamine E (DFO-E) secreted by streptomycetes bacteria can be an ideal candidate for iron chelation therapy, which necessitates its cost-effective production for in vitro and animal studies. This study focused on the optimization of DFO-E production by Streptomyces parvulus CBS548.68. Different combinations of various carbon and nitrogen sources as well as the addition of 3-morpholinopropane-1-sulfonic acid (MOPS) markedly affected DFO-E yields, which were attributed, at least in part, to the higher biomass productions found in MOPS-supplemented cultures. In MOPS-supplemented glucose and sodium glutamate medium, DFO-E productions as high as 2,009 ± 90 mg/l of culture medium were reached. High-performance liquid chromatography analysis demonstrated that a simple two-step purification process yielded DFO-E preparations with purities of ∼97%. Matrix assisted laser desorption ionization-time of flight mass spectrometry analysis showed that purified DFO-E always contained traces of desferrioxamine D2.

  20. Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron

    PubMed Central

    Alta, Roxana Y. P.; Vitorino, Hector A.; Goswami, Dibakar; Liria, Cleber W.; Wisnovsky, Simon P.; Kelley, Shana O.

    2017-01-01

    Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40–100 μM) and had good mitochondrial localization (Rr +0.45 –+0.68) as observed when labeled with carboxy-tetramethylrhodamine (TAMRA) In general, mtDFO caused only modest levels of mitochondrial DNA (mtDNA) damage. DFO-SS02 retained the antioxidant ability of the parent peptide, shown by the inhibition of mitochondrial superoxide formation. None of the compounds displayed cell cycle arrest or enhanced apoptosis. Taken together, these results indicate that mtDFO could be promising compounds for amelioration of the disease symptoms of iron overload in mitochondria. PMID:28178347

  1. Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil.

    PubMed Central

    Ferrali, M; Signorini, C; Ciccoli, L; Comporti, M

    1992-01-01

    Mouse erythrocytes were incubated with oxidizing agents, phenylhydrazine, divicine and isouramil. With all the oxidants a rapid release of iron in a desferrioxamine (DFO)-chelatable form was seen and it was accompanied by methaemoglobin formation. If the erythrocytes were depleted of GSH by a short preincubation with diethyl maleate, the release of iron was accompanied by lipid peroxidation and, subsequently, haemolysis. GSH depletion by itself did not induce iron release, methaemoglobin formation, lipid peroxidation or haemolysis. Rather, the fate of the cell in which iron is released depended on the intracellular availability of GSH. In addition, iron release was higher in depleted cells than in native ones, suggesting a role for GSH in preventing iron release when oxidative stress is imposed by the oxidants. Iron release preceded lipid peroxidation. The latter was prevented when the erythrocytes were preloaded with DFO in such a way (preincubation with 10 mM-DFO) that the intracellular concentration was equivalent to that of the released iron, but not when the intracellular DFO was lower (preincubation with 0.1 mM-DFO). Extracellular DFO did not affect lipid peroxidation and haemolysis, suggesting again that the observed events occur intracellularly (intracellular chelation of released iron). The relevance of iron release from iron complexes in the mechanisms of cellular damage induced by oxidative stress is discussed. PMID:1637315

  2. Stability of Commercial Lead in the Presence of Iron(III)-Sequestering Biogenic Ligands: Implications for Metal Mobility and Bioavailability in Natural Iron-Rich Environments

    NASA Astrophysics Data System (ADS)

    Cornejo-Garrido, H.; Fernández-Lomelin, P.; Guzman-Mendoza, J.; Sedov, S.; Cervini-Silva, J.

    2007-05-01

    Mexico is a leader in the production of lead. Exposure of soils contaminated with lead ore waste, ingestion of contaminated waters, or inhalation of suspended particles, among others are examples of common routes of exposure. Solubility often becomes limiting for Pb bioavailability, therein the need to further characterize natural processes that contribute to its mobility in the environment. In oxic environments, such as highly weathered soils or surficial seawater, microorganisms and higher plants produce biogenic ligands such as siderophores to mobilize Fe that otherwise would be unavailable. Siderophores ligands facilitate the dissolution of natural particles that represent a primary reservoir of iron. On the other hand, lead sorbs strongly to minerals, particularly to those bearing high contents of iron. Siderophore ligands have been identified to influence the adsorption behavior of Pb(II) on iron mineral surfaces. Yet, little is known on how siderophore ligands may affect the stability of Pb(0). In this paper we study the stability of Pb(0) in the presence of desferrioxamine (DFO-B), a common siderophore ligand. Batch dissolution experiments of Pb(0) (1 g L-1) in the presence of DFO-B ([DFO-B]0 ? 200M) at pH 5 were conducted for 7 days. The adsorption behavior of DFO-B was also characterized. Corresponding experiments in the absence of DFO-B for the purpose of comparison were also conducted. Analyses for soluble Pb were conducted by AA and ICP-AES. Solid characterization was conducted by XRD and SEM-EDX. Analyses for soluble Pb reveal concentrations of up to ca. 40 ppm. White small-sized particles were identified after reaction, regardless of the presence of DFO-B. The suspension chemical composition influenced colloidal stability. In the presence of DFO-B, forming solids showed small aspect ratio ( < 2m), while remained suspended in supernatant solutions. In the absence of DFO-B, solids formed showed varied in size. The were found to remain associated with

  3. The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads.

    PubMed

    Li, Jia; Fan, Lihong; Yu, Zefeng; Dang, Xiaoqian; Wang, Kunzheng

    2015-02-01

    In this study, we examined whether local deferoxamine (DFO) administration can promote angiogenesis and bone repair in steroid-induced osteonecrosis of the femoral head (ONFH). Steroid-induced ONFH was induced in 65 mature male New Zealand white rabbits by methylprednisolone in combination with lipopolysaccharide. Six weeks later, the rabbits received no treatment (model group, N = 15), bilateral core decompression (CD group, N = 20) or CD in combination with local DFO administration (DFO group, N = 20). Six weeks after the surgery, vascularization in the femoral head was evaluated by ink artery infusion angiography and immunohistochemical staining for von Willebrand Factor (vWF). Bone repair was assessed by histologic analysis and micro-computed tomography (micro-CT). Immunohistochemical staining was performed to analyze the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN). Ink artery infusion angiography and microvessel analysis by immuohistochemical staining for vWF showed more blood vessels in the DFO group than other groups. The expression of HIF-1α, VEGF, BMP-2, and OCN, indicated by immunohistochemical staining, was higher in the DFO group compared with other groups. Micro-CT scanning results indicated that the DFO group had larger volume of newly formed bone than the CD group. This work indicated that local DFO administration improved angiogenesis and bone repair of early stage ONFH in rabbit model, and it may offer an efficient, economic, and simple therapy for early stage ONFH.

  4. Consensus on surgical aspects of managing osteomyelitis in the diabetic foot

    PubMed Central

    Allahabadi, Sachin; Haroun, Kareem B.; Musher, Daniel M.; Lipsky, Benjamin A.; Barshes, Neal R.

    2016-01-01

    Background The aim of this study was to develop consensus statements that may help share or even establish ‘best practices’ in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data. Methods We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine-point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0. Results The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists’ agreement on general principles for surgical management of DFO. Conclusions Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as ‘best practice’ guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO. PMID:27414481

  5. Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles

    PubMed Central

    Tian, Wen; Sung, Yon K.; Sun, Wenchao; Hsu, Joe L.; Manickam, Sathish; Wagh, Dhananjay; Joubert, Lydia-Marie; Semenza, Gregg L.; Rajadas, Jayakumar; Nicolls, Mark R.

    2014-01-01

    Airway tissue ischemia and hypoxia in human lung transplantation is a consequence of the sacrifice of the bronchial circulation during the surgical procedure and is a major risk factor for the development of airway anastomotic complications. Augmented expression of hypoxia-inducible factor (HIF)-1α promotes microvascular repair and alleviates allograft ischemia and hypoxia. Deferoxamine mesylate (DFO) is an FDA-approved iron chelator which has been shown to upregulate cellular HIF-1α. Here, we developed a nanoparticle formulation of DFO that can be topically applied to airway transplants at the time of surgery. In a mouse orthotopic tracheal transplant (OTT) model, the DFO nanoparticle was highly effective in enhancing airway microvascular perfusion following transplantation through the production of the angiogenic factors, placental growth factor (PLGF) and stromal cell-derived factor (SDF)-1. The endothelial cells in DFO treated airways displayed higher levels of p-eNOS and Ki67, less apoptosis, and decreased production of perivascular reactive oxygen species (ROS) compared to vehicle-treated airways. In summary, a DFO formulation topically-applied at the time of surgery successfully augmented airway anastomotic microvascular regeneration and the repair of alloimmune-injured microvasculature. This approach may be an effective topical transplant-conditioning therapy for preventing airway complications following clinical lung transplantation. PMID:24161166

  6. Scavenging iron: a novel mechanism of plant immunity activation by microbial siderophores.

    PubMed

    Aznar, Aude; Chen, Nicolas W G; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

    2014-04-01

    Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H₂O₂ staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity.

  7. Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

    PubMed Central

    Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

    2014-01-01

    Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

  8. Orofacial Praxis Abilities in Children with Speech Disorders

    PubMed Central

    Bertagnolli, Ana Paula Coitino; Gubiani, Marileda Barichello; Ceron, Marizete; Keske-Soares, Márcia

    2015-01-01

    Introduction Phonological development occurs in a gradual manner until the age of 7 years. The phonological system is constructed in a similar way for all children, despite presenting some variations in terms of age, paths taken, or repair strategies used. Objective To compare the orofacial praxis abilities of children with typical phonological development (DFT), children with phonetic-phonological impairment (DFoFe), and children with phonological impairment (DF), using two tests to assess the orofacial praxis abilities. Methods The sample consisted of 82 subjects between 4 and 8 years of age who attended public schools (from preschool to the second year of secondary school) in the city of Santa Maria, Brazil. Of these, 29 were diagnosed with DFT, 29 with DF, and 24 with DFoFe; much of this sample was male. Two tests of praxis abilities and assessment of the stomatognathic system were administered. Statistical analysis was performed using the chi-square test, with a significance level of 5%. Results Generally children with DFoFe underperformed in tests of praxis when compared with subjects with DF and DFT. Conclusion The results showed that children with DFoFe have more difficulty in orofacial praxis abilities than subjects in the other groups studied. This result could be expected, because subjects with DFoFe show changes in both phonetic and phonological levels of speech. PMID:26491472

  9. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major.

    PubMed

    Borgna-Pignatti, Caterina; Cappellini, Maria Domenica; De Stefano, Piero; Del Vecchio, Giovanni Carlo; Forni, Gian Luca; Gamberini, Maria Rita; Ghilardi, Roberta; Piga, Antonio; Romeo, Maria Antonietta; Zhao, Huaqing; Cnaan, Avital

    2006-05-01

    Deferoxamine (DFO) therapy has been associated with improved survival of thalassemia patients. However, cardiac disease remains the main cause of death in those patients. In 1995, the oral chelator deferiprone became available for clinical use. We compared the occurrence of cardiac disease in patients treated only with DFO and in those whose therapy was switched to deferiprone during the period of observation, from January 31, 1995, to December 31, 2003. All patients with thalassemia major treated in 7 Italian centers who were born between 1970 and 1993 and who had not experienced a cardiac event prior to January 1995 were included. DFO only was given to 359 patients, and 157 patients received deferiprone for part of the time. A total of 3,610 patient-years were observed on DFO and 750 on deferiprone. At baseline, the 2 groups were comparable for age and sex, while ferritin levels were significantly higher in patients switched to deferiprone. Fifty-two cardiac events, including 10 cardiac deaths, occurred during therapy with DFO. No cardiac events occurred during deferiprone therapy or within at least 18 months after the end of it. In the setting of a natural history study, deferiprone therapy was associated with significantly greater cardiac protection than deferoxamine in patients with thalassemia major.

  10. VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization

    PubMed Central

    Wahl, Elizabeth A.; Schenck, Thilo L.; Machens, Hans-Günther; Balmayor, Elizabeth R.

    2016-01-01

    Hypoxia preconditioning of mesenchymal stem cells (MSCs) has been shown to promote wound healing through HIF-1α stabilization. Preconditioned MSCs can be applied to three-dimensional biomaterials to further enhance the regenerative properties. While environmentally induced hypoxia has proven difficult in clinical settings, this study compares the wound healing capabilities of adipose derived (Ad) MSCs seeded on a collagen-glycosaminoglycan (GAG) dermal substrate exposed to either environmental hypoxia or FDA approved deferoxamine mesylate (DFO) to stabilize HIF-1α for wound healing. The release of hypoxia related reparative factors by the cells on the collagen-GAG substrate was evaluated to detect if DFO produces results comparable to environmentally induced hypoxia to facilitate optimal clinical settings. VEGF release increased in samples exposed to DFO. While the SDF-1α release was lower in cells exposed to environmental hypoxia in comparison to cells cultured in DFO in vitro. The AdMSC seeded biomaterial was further evaluated in a murine model. The implants where harvested after 1 days for histological, inflammatory, and protein analysis. The application of DFO to the cells could mimic and enhance the wound healing capabilities of environmentally induced hypoxia through VEGF expression and promises a more viable option in clinical settings that is not merely restricted to the laboratory. PMID:27830734

  11. Rapid excretion of gallium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine

    SciTech Connect

    Baker, D.L.; Manno, C.S.

    1988-12-01

    A 23 year-old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga-67), which was initially nondiagnostic because of Ga-67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney. To our knowledge the unusual interaction in vivo of DFO with Ga-67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga-67 scanning in this clinical situation, or an alternative isotopic scan, such as indium-labelled white cells, should be considered.

  12. Environmental Actinide Mobility: Plutonium and Uranium Interactions with Exopolysaccharides and Siderophores of Aerobic Soil Microbes

    SciTech Connect

    Neu, Mary P.; Vanderberg, Laura

    2001-06-01

    Research efforts into understanding the effect of siderophores and capsules on actinide speciation and resultant environmental behavior are ongoing. Investigations on both siderophores have progressed. The redox chemistry of Pu(VI) and Pu(V) with DFO under acidic conditions was examined by UV-Vis and NMR spectroscopies. Pu(VI) was instantly reduced to Pu(V) by DFO and DFO cleavage resulted. Neither DFO nor the cleavage product appeared to coordinate with Pu(V) in the pH range examined. Growth of S. pilosus for cellular translocation experiments was optimized and experiments to determine DFO-mediated uranium uptake by S. pilosus are underway. OFS siderophore(s) production has been optimized and product identification is underway. Siderophore-like molecules were positive for the Arnow assay and had UV absorbance bands at 250nm and 315nm, suggesting catecholates-type molecules. Siderophores were produced with C13 - C16 as carbon source in AM-1 salts medium with 1.0mM iron. Siderophore accumulation was slowest on C13 due to the slower growth of OFS on this substrate. The C16 concentration in the culture influenced siderophore production, with highest levels at 1.0% and 2.0%.

  13. Protective effects of desferrioxamine and deferiprone on the spleen tissue of aluminum intoxicated mice: A Fourier transform infrared spectroscopy study

    NASA Astrophysics Data System (ADS)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.

    The present study was designed to examine the protective effects of the chelating agents desferrioxamine (DFO) and deferiprone (DFP) in aluminum intoxicated spleen tissue of mice by Fourier transform infrared (FTIR) spectroscopy. The finding revealed the alterations on the major biochemical constituents, such as lipids, proteins, phosphodiester and nucleic acids of the spleen tissue of mice at molecular level. The significant decreased in the peak areas of asymmetric and symmetric mode of the phosphodiester groups from control to aluminum intoxicated, but improved it by DFP and DFO + DFP treatments respectively for nearer control value. The bands ratio at I1081/I1232 significantly decreased from control to aluminum, but enhanced it by DFP and DFO + DFP respectively. This result suggests that DFO and DFP are the phosphodiesterase inhibitor, recovered from chronic growth of diseases in the spleen. Amide I and amide II peak area values decreased from control to aluminum intoxicated spleen tissue, but treated with DFP and DFO + DFP significantly improved. This result suggests an alteration in the protein profile. The absence of Olefinicdbnd CH stretching in aluminum intoxicated spleen suggests an altered lipid levels. Concentrations of trace elements were found by ICP-OES. Histopathological findings confirmed the biochemical observations of this study. The results of the FTIR study were found to be in agreement with biochemical studies and demonstrated that FTIR can be used successfully applied to toxicological studies at molecular level.

  14. Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats.

    PubMed

    Emara, A M; El Kelany, R S; Moustafa, K A

    2006-07-01

    Patients with iron overload frequently suffer from hemochromatosis of major organs, such as the heart and liver. Heart affection is the most common cause of death in patients with iron overload. Although the beneficial effects of deferoxamine (DFO) on iron-associated mortality are well documented, the role of deferiprone in the management of transfusional iron overload is controversial. The aim of this study was to compare the protective effect of iron chelators (DFO and deferiprone) individually and in combination with the anti-oxidant (vitamin C) in the prevention of myocardial damage. Sixty albino rats were divided into six groups: two control groups (noniron-loaded and iron-loaded) and four iron-loaded groups classified as follows: DFO group, DFO combined with vitamin C group, deferiprone group and deferiprone combined with vitamin C group. Heart tissue and blood samples were taken for histopathological examination of the heart, determination of total iron-binding capacity, 8-OH-deoxyguanosine (8-OH-dG), myocardial lipid peroxidation and glutathione (GSH) content. Less histopathological cardiac changes and a significant decrease in all biochemical parameters, except myocardial GSH, were observed in the deferiprone group. The addition of vitamin C improves the biochemical and histopathological changes in comparison to those rats administered DFO or deferiprone individually.

  15. Effect of iron chelators on placental uptake and transfer of iron in rat

    SciTech Connect

    Wong, C.T.; McArdle, H.J.; Morgan, E.H.

    1987-05-01

    The uptake of radiolabeled transferrin and iron by the rat placenta has been studied using two approaches. The first involved injection of a ferrous or ferric iron chelator followed by injection of label. Neither chelator decreased the amount of labelled transferrin in the placenta after 2-h incubation and only bipyridine, a ferrous iron chelator, inhibited iron transport to the fetus. Deferoxamine (DFO), a ferric iron chelator, had no effect on iron transport to the fetus but reduced iron uptake by the liver. Both bipyridine and DFO increased iron excretion into the gut and by the urinary tract to the same degree into the gut, but there was a 10-fold greater urinary excretion with bipyridine than with DFO. Injection of iron attached to the chelators showed that neither bipyridine nor DFO could donate iron to the fetus as efficiently as transferrin. The mechanism involved was further investigated by studying the effect of the chelators on uptake of transferrin-bound iron by placental cells in culture. DFO inhibited iron accumulation more effectively than bipyridine in the cultured cells. The effect was not due to a decrease in the cycling time of the receptor. The results can be explained if the iron is released from the transferrin in intracellular vesicles in the ferrous form, where it may be chelated by bipyridine and prevented from passing to the fetus or converted to the ferric form once it is inside the cell matrix.

  16. Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells.

    PubMed

    Hegde, Narasimha V; Jensen, Gordon L; Unger, Erica L

    2011-02-15

    Cell surface expression of the dopamine transporter (DAT) is determined by the relative rates of its internalization and recycling. Changes in the cellular labile iron pool (LIP) affect many cellular mechanisms including those that regulate DAT trafficking. In this study, we analyzed DAT expression and posttranslational modifications in response to changes in cellular iron in transfected neuroblastoma cells (N2a). Iron chelation by desferrioxamine (DFO) altered DAT protein levels by decreasing the stability of DAT mRNA. Increased phosphorylation and ubiquitination of this transporter protein following DFO treatment were also observed. Cellular iron depletion elevated protein levels of the early endosomal marker Rab5. Moreover, confocal microscopy studies showed increased localization of DAT into the endosomal compartment in DFO-treated cells compared to control. Together, these findings suggest that cellular iron depletion regulates DAT expression through reducing mRNA stability as well as an increasing in endocytosis.

  17. Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy

    PubMed Central

    Donneys, Alexis; Nelson, Noah S.; Page, Erin E.; Deshpande, Sagar S.; Felice, Peter A.; Tchanque–Fossuo, Catherine N.; Spiegel, Joshua P.; Buchman, Steven R.

    2016-01-01

    Background Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. Methods Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35 Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons. Results Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy. Conclusion Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT. PMID:24801669

  18. SERS Activity of Silver Nanoparticles Functionalized with A Desferrioxamine B Derived Ligand for FE(III) Binding and Sensing

    NASA Astrophysics Data System (ADS)

    Galinetto, P.; Taglietti, A.; Pasotti, L.; Pallavicini, P.; Dacarro, G.; Giulotto, E.; Grandi, M. S.

    2016-01-01

    We report the SERS activity of colloidal silver nanoparticles functionalized with a ligand, derived from the siderophore desferrioxamine B (desferal, DFO), an iron chelator widely used in biological and medical applications. The ligand was equipped with a sulfur-containing moiety to ensure optimal binding with silver surfaces. By means of Raman and SERS effects we monitored the route of material preparation from the modified DFO-S molecule to the colloidal aggregates. The results indicate that the functionalization of the chelating agent does not affect its binding ability towards Fe(III). The resulting functionalized silver nanoparticles are a promising SERS tag for operation in biological environments. The Fe-O stretching signature, arising when DFO-S grafted to silver nanoparticles binds Fe(III), could provide a tool for cation sensing in solution.

  19. Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.

    PubMed Central

    Merali, S; Chin, K; Grady, R W; Weissberger, L; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine mesylate (DFO) is active against Pneumocystis carinii in vitro and in rat and mouse models of P. carinii pneumonia. Because DFO has a short half-life, daily divided or continuous dosage was expected to improve the dose response, as is the case with DFO treatment of malaria. Therefore, results of single daily intraperitoneal injections were compared with results of an evenly divided four-times-daily dosage and the efficacy of delivery with implanted infusion pumps. The highest bolus dosage (1,000 mg kg-1 of body weight day-1) was as effective as the standard combination of trimethoprim with sulfamethoxazole. Unexpectedly, very little improvement was observed with the divided or continuous dosage, and several mechanisms that could account for this are discussed. PMID:7492082

  20. Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in -thalassemia major patients.

    PubMed

    Pantalone, Gaetano Restivo; Maggio, Aurelio; Vitrano, Angela; Capra, Marcello; Cuccia, Liana; Gagliardotto, Francesco; Filosa, Aldo; Romeo, Maria Antonietta; Magnano, Carmelo; Caruso, Vincenzo; Argento, Crocetta; Gerardi, Calogera; Campisi, Saveria; Violi, Pietro; Malizia, Roberto; Cianciulli, Paolo; Rizzo, Michele; D'Ascola, Domenico Giuseppe; Quota, Alessandra; Prossomariti, Luciano; Fidone, Carmelo; Rigano, Paolo; Pepe, Alessia; D'Amico, Gennaro; Morabito, Alberto; Gluud, Christian

    2011-01-01

    In β-thalassemia major (β-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO vs. L1 alone iron chelation therapy in β-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during a 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin level was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients (p = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences (log-rank test, p = 0.3145). Adverse events and costs were comparable between the groups. Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone, without significant differences of survival, adverse events or costs. These findings were confirmed in a further 21-month follow-up. These data suggest that alternating sequential L1-DFO treatment may be useful for some β-TM patients who may not be able to receive other forms of chelation treatment.

  1. Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies.

    PubMed

    Maggio, Aurelio; Vitrano, Angela; Capra, Marcello; Cuccia, Liana; Gagliardotto, Francesco; Filosa, Aldo; Magnano, Carmelo; Rizzo, Michele; Caruso, Vincenzo; Gerardi, Calogera; Argento, Crocetta; Campisi, Saveria; Cantella, Francesco; Commendatore, Francesca; D'Ascola, Domenico Giuseppe; Fidone, Carmelo; Ciancio, Angela; Galati, Maria Concetta; Giuffrida, Gaetano; Cingari, Rocca; Giugno, Giovanni; Lombardo, Turi; Prossomariti, Luciano; Malizia, Roberto; Meo, Anna; Roccamo, Gaetano; Romeo, Maria Antonietta; Violi, Pietro; Cianciulli, Paolo; Rigano, Paolo

    2009-01-01

    The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone-deferoxamine (DFP-DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared deferoxamine (DFO) versus DFP alone, sequential DFP-DFO, or combined DFP-DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP-DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP-DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant (p-value<0.013). For each increasing year of age, the hazard ratio for males was 1.03 higher than that for females (p-value<0.013). In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are deferoxamine

  2. A comparative study on the enhancement efficacy of specific and non-specific iron chelators for protoporphyrin IX production and photosensitization in HaCat cells.

    PubMed

    Xia, Yumin; Huang, Yingying; Lin, Longde; Liu, Xiaoming; Jiang, Shan; Xiong, Layuan

    2009-12-01

    The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT). The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular protoporphyrin IX (PpIX) was detected by high performance liquid chromatography (HPLC), and the fluorescence of PpIX was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpIX and the fluorescent density of PpIX, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpIX level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpIX production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.

  3. Mechanism Governing Human Kappa-Opioid Receptor Expression under Desferrioxamine-Induced Hypoxic Mimic Condition in Neuronal NMB Cells

    PubMed Central

    Babcock, Jennifer; Herrera, Alberto; Coricor, George; Karch, Christopher; Liu, Alexander H.; Rivera-Gines, Aida; Ko, Jane L.

    2017-01-01

    Cellular adaptation to hypoxia is a protective mechanism for neurons and relevant to cancer. Treatment with desferrioxamine (DFO) to induce hypoxia reduced the viability of human neuronal NMB cells. Surviving/attached cells exhibited profound increases of expression of the human kappa-opioid receptor (hKOR) and hypoxia inducible factor-1α (HIF-1α). The functional relationship between hKOR and HIF-1α was investigated using RT-PCR, Western blot, luciferase reporter, mutagenesis, siRNA and receptor-ligand binding assays. In surviving neurons, DFO increased HIF-1α expression and its amount in the nucleus. DFO also dramatically increased hKOR expression. Two (designated as HIFC and D) out of four potential HIF response elements of the hKOR gene (HIFA–D) synergistically mediated the DFO response. Mutation of both elements completely abolished the DFO-induced effect. The CD11 plasmid (containing HIFC and D with an 11 bp spacing) produced greater augmentation than that of the CD17 plasmid (HIFC and D with a 17 bp-spacing), suggesting that a proper topological interaction of these elements synergistically enhanced the promoter activity. HIF-1α siRNA knocked down the increase of endogenous HIF-1α messages and diminished the DFO-induced increase of hKOR expression. Increased hKOR expression resulted in the up-regulation of hKOR protein. In conclusion, the adaptation of neuronal hKOR under hypoxia was governed by HIF-1, revealing a new mechanism of hKOR regulation. PMID:28117678

  4. Essays on Strategy. 4.

    DTIC Science & Technology

    1987-01-01

    the costs to a level to make deterrence work. Aaron Freidberg cautions us, "It is worth remembering that a nuclear war of virtually any size or...University, May 1983, p. 254. 60 STRA TEGY IMPLICA TIONS OF SDI 15. Aaron L. Freidberg , "A History of the U.S. Strategic Doctrine, 1945-1970," Military...Brassey’s International Defense Publisher, 1984, p. 13. 19. Freidberg , "A History of the U.S. Strategic Doctrine," p. 143. 20. Record, "Revising U.S

  5. Phenomenology of Structured Plasma in the Ionosphere.

    DTIC Science & Technology

    1983-03-01

    SCINTILLATIONS Author(s) Place Frequency Observations Maxim Aarons et al. Accra, Ghana 257 MHz 01/77 - 03/78 Feb-Apr [1980] Huancayo , Peru 257 MHz 01...77 - 03/78 Feb-Apr Natal, Brazil 257 Mz 01/77 - 03/78 Nov-Jan Guam’U.S. 257 MHz 03/78 - 06/79 Feb-Jul Bandvopadhvav and Aarons [1970] Huancayo , Peru...137 MHz 07/67 - 02/69 Sep-Nov Basu et al. [1980] Huancayo , Peru 1543 MHz 04/76 - 10/77 Mar,Oct Chatteriee et al. [1974] Huancayo , Peru 137 MHz 05/67

  6. XAFS Determination of Pb and Cd Speciation with Siderophores and the Metal/Siderophore/Kaolinite System

    SciTech Connect

    Mishra, Bhoopesh; Haack, Elizabeth A.; Vasconcelos, Igor F.; Maurice, Patricia A.; Bunker, Bruce A.

    2008-06-16

    We provide evidence for hexadentate complexes of Pb{sup 2+} and Cd{sup 2+} with the trihydroxamate siderophore desferrioxamine B (DFO-B) at pH 7.5, and 9.0, respectively. Analysis of the species of Pb{sup 2+} and Cd{sup 2+} adsorbed at the surface of kaolinite clay under the same pH conditions and in the presence of DFO-B indicate that Pb{sup 2+} is sorbed as a metal-siderophore complex while Cd{sup 2+} is not.

  7. 75 FR 46938 - Ocean Transportation Intermediary License Applicants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Intermediaries, Federal Maritime Commission, Washington, DC 20573. Aaron P.B. Production Corporation (NVO & OFF... Logistics (OFF), 1322 E. Pacific Coast Highway, Suite B, Wilmington, CA 90744, Officers: Ernie R. Zavaleta... & OFF License. Prime Van Lines, Inc. (OFF), 297 Getty Avenue, Paterson, NJ 07503, Officers: Robert...

  8. Friendship and the Public Stage: Revisiting Hannah Arendt's Resistance to "Political Education"

    ERIC Educational Resources Information Center

    Schutz, Aaron; Sandy, Marie G.

    2015-01-01

    Hannah Arendt's essays about the 1957 crisis over efforts of a group of youth, the "Little Rock Nine," to desegregate a high school in Little Rock, Arkansas, reveal a tension in her vision of the "public." In this article Aaron Schutz and Marie Sandy look closely at the experiences of the youth desegregating the school,…

  9. The Lighter Side of Staff Development

    ERIC Educational Resources Information Center

    Bacall, Aaron

    2004-01-01

    As educators, we often take ourselves a bit too seriously, so veteran educator and illustrator Aaron Bacall offers a little perspective with these lighthearted cartoons. Whether used as overheads for meetings or as an individual break in a busy day, this collection of whimsical glimpses at staff development will provide a moment to laugh and add a…

  10. Views of the STS-5 Science Press briefing with Student Experimenters

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Views of the STS-5 Science Press briefing with Student Experimenters. Photos include Michelle Issel of Wallingfor, Connecticut showing her studen experiment dealing with the formation of crystals in a weightless environment (37862); Aaron Gillette of Winter Haven, Florida displaying his student experiment dealing with the growth of Porifera in zero gravity (37863).

  11. Future Generation Network Architecture (New Arch)

    DTIC Science & Technology

    2004-06-01

    Kulik, Xiaowei Yang, Robert Braden, Ted Faber, Aaron Falk, Venkata Pingali, Mark Handley, Noel Chiappa , Steve Bellovin 5. FUNDING NUMBERS C...independent contributor (Noel Chiappa ). This report is a combined final report on the work done at MIT and at ISI, since the effort was highly

  12. New ARCH: Future Generation Internet Architecture

    DTIC Science & Technology

    2004-08-01

    Joanna Kulik, Xiaowei Yang, Ted Faber, Aaron Falk, Venkata Pingali, Mark Handley, Noel Chiappa 5. FUNDING NUMBERS C - F30602-00-2-0553 PE...and an independent contributor (Noel Chiappa ). This report is a combined final report on the work done at MIT and at ISI, since the effort was

  13. Modern Czech Studies. Brown Slavic Contributions, Volume XIII.

    ERIC Educational Resources Information Center

    Levitsky, Alexander, Ed.; Fidler, Masako U., Ed.

    2000-01-01

    The following papers are included: "Responses to the Literature Papers" (Malynne M. Sternstein); "Kitsch and Irony in Kundera: 'The Joke' and 'The Unbearable Lightness of Being'" (Aaron Beaver); "Daniela Fischerova's 'The Message Table': (Lauren McConnell); "Rethinking the Grotesque in Hrabal's Fiction" Carnival…

  14. 78 FR 18565 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ...: March 21, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense... Disability Agency, Walter Reed Army Medical Center, 6900 Georgia Avenue NW., Building 7, Washington, DC 20307... retires. System manager(s) and address: Chief, U.S. Army Physical Disability Agency, Walter Reed...

  15. 77 FR 68744 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    .... Welcome and Member Introductions 8:45 a.m.-9:30 a.m. Walter Reed Installation Visit Review 9:30 a.m.-9:45..., Tuesday, November 27, 2012. Dated: November 13, 2012. Aaron Siegel, Alternate OSD Federal Register...

  16. 77 FR 23797 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    .... Irvin (MA) Neil W. Jennings (MO) Mark L. LeBlanc (MN) David A. Miller (IA) Richard W. Neyens (WA) Paul D. Schnautz (TX) Steve J. Sherar (AZ) Robert R. Skinner, Jr. (NY) William T. Smiley (MD) Richard M. Smith (CO) David N. Stubbs (MS) Edward J. Sullivan (NH) Martin L. Taylor (UT) Aaron S. Taylor (WI) William...

  17. 75 FR 61775 - Exemptions From Certain Prohibited Transaction Restrictions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ... not apply effective for the period from January 29, 2010, through June 30, 2010, to the lease (the Lease) by the Fund from the NERCC, LLC (the Building Corporation), a party in interest with respect to... to entering into the Lease, the Fund sought legal advice from Aaron D. Krakow, Esq. (Mr....

  18. Novel Optical Metamaterials and Approaches for Fabrication

    DTIC Science & Technology

    2012-08-01

    AFRL-RY-WP-TR-2012-0250 NOVEL OPTICAL METAMATERIALS AND APPROACHES FOR FABRICATION Alkim Akyurtlu, Joel Therrien , and Aaron Bandremer...FABRICATION 5a. CONTRACT NUMBER FA8718-07-C-0054 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62204F 6. AUTHOR(S) Alkim Akyurtlu, Joel Therrien

  19. Data Reduction and Analysis-Experimental IEMP/SGEMP Electron Beam Study, First Interim Report: 40 KEV Beam Energy

    DTIC Science & Technology

    1975-12-01

    fixed pressure for each shot. The pressure range explored extended from less than one micron. to, in some instances, twenty torr . The time histories of...United Technologies Corporation ATTN: Jerry 1. Lulbell Norden Division ATTN: Aaron H. Narevaky. RI-2144 ArTN: Conrad Cord% ATTN. Lillian D. Singletary

  20. 77 FR 71173 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... the Military Health System (MHS) with a comprehensive enterprise wide Blood Donor Management System... the instructions for submitting comments. Mail: Federal Docket Management System Office, 4800 Mark... Management System (DHIMS), ATTN: COL Aaron J. Silver, 5109 Leesburg Pike, Skyline 6, Suite 703, Falls...

  1. 77 FR 67345 - Final Environmental Impact Statement/Environmental Impact Report (EIS/EIR) for the Clearwater...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... by the Sanitation Districts for the Joint Outfall System, a regional wastewater management system.... The document is accessible via the World- Wide Web at www.ClearwaterProgram.org . Alternatively... Information Contact: Questions or comments concerning the Final EIS/EIR should be directed to Dr. Aaron...

  2. Advances in Preventing Childhood and Adolescent Problem Behavior

    ERIC Educational Resources Information Center

    Jenson, Jeffrey M.

    2010-01-01

    Recent advances in the field of prevention have led to a deeper understanding of the causes of adolescent problem behavior and to the identification of efficacious strategies to prevent delinquency, drug use, and other antisocial conduct. This 2009 Aaron Rosen lecture to members of the "Society for Social Work and Research" traces the evolution of…

  3. Analytical Modeling of High Rate Processes

    DTIC Science & Technology

    1997-12-01

    be related thereto. The technical report has been reviewed and is approved for publication. FOR THE COMMANDER AARON D.BRINSON RUSS KLUG , Program...MNMW) 101 W. Eglin Blvd., Ste 239 Program Manager, EglinAFB, FL 32542-6810 (850) 882- Russ Klug 9643 x202 5. FUNDING NUMBERS C: F08630-93-K-0011

  4. "The Social Network" and the Legal Environment of Business: An Opportunity for Student-Centered Learning

    ERIC Educational Resources Information Center

    McGill, Shelley

    2013-01-01

    Aaron Sorkin has a passion for words--his signature movie and television scripts are fast talking, jargon laced, word pictures that are instantly recognizable. "The Social Network," Sorkin's 2011 Academy Award Winning movie about the founding of Facebook, Inc., offers more than just witty banter; it provides an ideal teaching platform for…

  5. A Comparison of 15 Theories of Suicide.

    ERIC Educational Resources Information Center

    Lester, David

    1994-01-01

    Studied lives of suicidal individuals by operationalizing each of 15 theories of suicide with 10 statements and rating these 150 statements as present or absent in lives of 30 famous suicides for whom biographies were available. Theory of Aaron Beck was found to be most applicable to suicidal lives and that of Freud was least applicable.…

  6. Healthy Thinking: A Group Approach.

    ERIC Educational Resources Information Center

    Rosenbaum, Janet N.; Carty, Laurie

    1994-01-01

    A "Healthy Thinking" group, based on a modified Aaron Beck Cognitive Therapy model, teaches depressed clients to realistically appraise their experiences by monitoring and changing distorted thinking. Clients learn that situational stress activates long held assumptions (negative beliefs) leading to distorted thinking and ultimately…

  7. Environmental Issues in Brazilian Society. Fulbright-Hays Seminars Abroad Program. June 26-July 31, 1994.

    ERIC Educational Resources Information Center

    Commission for Educational Exchange between the United States and Brazil, Brasilia.

    This book contains a review of the 1994 Fulbright-Hays Seminars Abroad Program along with lesson plans from 13 of the participants. The curriculum projects contained in this book include: (1) "The Brazilian Cinema: A Critical Appreciation of An Industry in Turmoil" (Aaron Braun); (2) "Reflections on the Relationship between…

  8. Scalable and Accurate SMT-Based Model Checking of Data Flow Systems

    DTIC Science & Technology

    2013-10-31

    theories competition. http://www.smtcomp.org/2010/. [4] Clark Barrett, David Dill , and Jeremy Levitt. Validity checking for combinations of theories with...Satisfiability Modulo Theories, SMT ’09, pages 6–13, New York, NY, USA, 2009. ACM. [19] Aaron Stump, Clark W. Barrett, and David L. Dill . CVC: A cooper- ating

  9. Turn off the Television and Read

    ERIC Educational Resources Information Center

    Hodapp, Albert Fed

    2016-01-01

    Aaron (2005) described the "family as the nation's smallest school" and "the home as the first school." Furthermore, studies document that 90% of the differences in academic achievement can be explained by five factors: (a) two-parent households; (b) school absenteeism; (c) amount read for homework; (d) quality and quantity of…

  10. Adult Fans of Comic Books: What They Get out of Reading

    ERIC Educational Resources Information Center

    Botzakis, Stergios

    2009-01-01

    This interview study is an exploration of the popular cultural and lifelong literacy practices of adult readers of comic books. Focusing on 4 participants from a pool of 12, the researcher used Kvale's (1996) method of meaning interpretation to analyze utterances and speak to the various uses reading held for these people. Aaron, Kyle, Peter, and…

  11. Engl 1102: Literature and Composition: Handwriting and Typography

    ERIC Educational Resources Information Center

    Kashtan, Aaron

    2015-01-01

    Aaron Kashtan taught three sections of ENGL 1102, the second course in a mandatory first-year writing sequence with a heavy multimodal focus, during his first semester as a Marion L. Brittain Postdoctoral Fellow in the Department of Literature, Media and Communication at Georgia Tech. The specific subject matter for these sections was handwriting…

  12. Capability Maturity Model (Trademark) Integration (CMMI (Service Mark)), Version 1.1. CMMI (Service Mark) for Software Engineering (CMMI-SW, V1.1)

    DTIC Science & Technology

    2002-08-19

    Gunning, Kelly Morin, Joseph F. Boeing Jacobs Sverdrup Advanced Systems Group Beshore, David Dutton, Jeffrey L. Brayer, Gil KPMG Consulting...Bill Guerin, Joan Menezes, Winifred Hayes, Will Raytheon Hertneck, Christian Berauer, Ben Johnson, Martha Clouse, Aaron Jones, Larry Moon, Jane...Gallagher, Brian Curtis, Bill Garcia , SuZ THALES Gibson, Diane Bonnet, Thierry Goldenson, Dennis Cattan, Denise Graffius, Joe Des Rochettes, Gilles

  13. Reconstructing NATO Strategy for the 1990s

    DTIC Science & Technology

    1989-08-01

    Mason Thomson International David Omand British NATO Mission Sir Michael Quinlan Ministry of Defence John Roper Royal Institute of International Affairs...United States of America David Aaron Robin Beard Lynwood Associates, Ltd. Richard Bitzinger The RAND Corporation Richard Burt U.S. Ambassador to the

  14. Tissue Engineering and Regenerative Medicine

    DTIC Science & Technology

    2006-11-01

    Mark Furth Mark Van Dyke Shay Soker Steve Hodges Weixin Zhao YuanYuan Zhang Aaron Goldstein Alan Farney Ann Gleeson Ann Immekus Ben Watts Callie Crider...Myers Robyn Shaffer Saami Yazdani Samira Neshat Sang Jin Lee Sergio Rodriguez Shirin Zare So-Young Chun Steve Schultz Tamer AbouShawreb Tao Xu Ted Kincaid

  15. Move Over, SI: Minority Sports Magazine to Debut at Year's End

    ERIC Educational Resources Information Center

    Yates, Eleanor Lee

    2004-01-01

    A new magazine focusing exclusively on issues facing Black, Hispanic and other athletes of color is set to hit the news-stands at the end of the year. "The Color of Sports can fill a significant void and have a tremendous influence on shaping the agenda of the sports industry," says Aaron Brooks, one of the magazine's investors and quarterback for…

  16. Reflexivity and Transnational Habitus: The Case of a "Poor" Affluent Chinese International Student

    ERIC Educational Resources Information Center

    De Costa, Peter I.; Tigchelaar, Magda; Cui, Yaqiong

    2016-01-01

    Following Sayer's (2010) examination of reflexivity and habitus, we focus on the "transnational habitus" (Darvin & Norton 2015) of Aaron, a Chinese international student at a U.S. university. Specifically, we examine how he wrestled with being identified as an ESL learner despite having attended a U.S. high school. Also exploring the…

  17. Magna Carta for Community: Bay Mills Charters Schools throughout Michigan

    ERIC Educational Resources Information Center

    Reynolds, Jerry

    2009-01-01

    For most of a full career in sociology and education, Aaron Tadgerson has dwelt on the relationship between communities and the school systems that purport to serve them. The special problems of Indian education derive from that relationship. Tadgerson serves as the recruiter, retention, and land grant development coordinator for Bay Mills…

  18. Word Calling in 3rd and 4th Graders: Exploring Student and Teacher Characteristics

    ERIC Educational Resources Information Center

    Couzens, Lindsay Starr

    2013-01-01

    Reading difficulties in elementary school-aged children may occur when two components of reading--word identification, comprehension, or both of these skills--are weak or underdeveloped (Gough, 1972; Hoover & Gough, 1990; Joshi & Aaron, 2000; Savage, 2001). One type of reading difficulty that is frequently identified by teachers is known…

  19. Developing the Vertex Formula Meaningfully

    ERIC Educational Resources Information Center

    Nebesniak, Amy L.; Burgoa, A. Aaron

    2015-01-01

    As teachers working with students in entry-level algebra classes, authors Amy Nebesniak and A. Aaron Burgoa realized that their instruction was a major factor in how their students viewed mathematics. They often presented students with abstract formulas that seemed to appear out of thin air. One instance occurred while they were teaching students…

  20. Travel to Learn: How, When, and Why to Apply for Overseas Professional Development

    ERIC Educational Resources Information Center

    Cook, Erika; Becker, Aaron

    2013-01-01

    In this article, Erika Cook and Aaron Becker suggest teachers travel to "unfamiliar" lands to not only breathe life into global lessons but also to gain new perspectives and experiences as educators. For teachers who dread teaching about an unfamiliar place or culture, Cook and Becker recommend considering the very real opportunities to…

  1. Eastern Renewable Generation Integration Study: Redefining What’s Possible for Renewable Energy

    SciTech Connect

    Bloom, Aaron

    2016-06-14

    NREL project manager Aaron Bloom introduces NREL’s Eastern Renewable Generation Integration Study (ERGIS) and high-performance computing capabilities and new methodologies that allowed NREL to model operations of the Eastern Interconnection at unprecedented fidelity. ERGIS shows that the Eastern Interconnection can balance the variability and uncertainty of wind and solar photovoltaics at a 5-minute level, for one simulated year.

  2. Internal Revenue Service General Counsel's Memorandum threatens tax exemption for charitable hospitals.

    PubMed

    Ball, D W

    1992-01-01

    A recent memorandum from the General Counsel of the Internal Revenue Service changes the standard against which tax exempt entities will be measured, which change can adversely affect charitable hospitals' tax exempt status. In addition, the memorandum makes clear that a violation of the Anti-Kickback statute, discussed in Mr. Aaron's article, is inconsistent with tax exempt status.

  3. Living the Dream of Green Acres: Boy with Autism Finds Acceptance and Success Thanks to 4-H

    ERIC Educational Resources Information Center

    Richardson, Ginny

    2006-01-01

    Twelve-year-old Aaron Zibricky, a member of the Lucky Clovers 4-H Club, entered his prize sheep, Star, in the 2005 Will County Fair in Illinois. Zibricky, who is diagnosed with autism, had worked and strived for this moment, putting in long hours feeding, cleaning and shearing the sheep and learning showmanship skills. No one was more elated at…

  4. Navy and Marine Corps Spectrum Offices (NMCSO) Status

    DTIC Science & Technology

    2012-03-01

    IT1 Aaron Crawford IT1 William Kennedy IT1 Trinika Savage Randall Hall (Supervisor) Dave Harris ITC Duane King IT1...VACANT E6 Gary Vogel (Supervisor) Greg Boone ITC James Robinson Rena Karas (Supervisor) Elizabeth Anderson Reginald Thomas...states and afloat. NMCSO (South West) San Diego (Supr Rena Karas )  COOP - NAVMARSPECCEN or NMCSO LANT office operations during contingencies

  5. Salutogenesis 30 Years Later: Where Do We Go from here?

    ERIC Educational Resources Information Center

    Becker, Craig M.; Glascoff, Mary Alice; Felts, W. Michael

    2010-01-01

    In 1979 Aaron Antonovsky introduced the concept of salutogenesis as the study of health development. This approach contrasted with the concept of pathogenesis or the study of disease development. Pathogenesis works retrospectively from disease to determine how individuals can avoid, manage, and/or eliminate that disease. Salutogenesis works…

  6. Pakistan’s and Palestine’s Role in Promoting Violent Ideological Education

    DTIC Science & Technology

    2009-04-01

    Reforming the Education Sector. International Crisis Group, 7 October 2004. Pina , Aaron D. Palestinian Education and the Debate Over Textbooks...Education Reform, 2 6 Kronstadt, Pakistan-U.S. Relations, 76 7 Brown, Palestinian National Authority, 125 8 Pina , Palestinian Education, 2 9...Israeli, Educating Palestinian Childen, 84 10 Pina , Palestinian Education, , 13 11 Israeli, Educating Palestinian Children, 91 12 Fair, The

  7. User Evaluation of a Bone Conduction Communication Headset During the Patriot 2007 Joint Field Training Exercise

    DTIC Science & Technology

    2012-04-01

    U.S. ARMY - NATICK SOLDIER SYSTEM CENTER DAVID AARON PHELPS SSG KANSAS STREET NATICK MA 01760-5020 4 U.S. ARMY – PM SOLDIER WARRIOR MARIO...SCOTT SENTER CTR 10125 KINGMAN ROAD FT. BELVOIR VIRGINIA 22060-5820 1 U.S. ARMY - PM SEQ MICHAEL VAN BUSKIRK 10170 BEACH RD., BLDG 328T FT

  8. The Technology of Unequal Rights for Women: Patent Drawings of a Voting Machine

    ERIC Educational Resources Information Center

    Hussey, Michael

    2008-01-01

    In 1878, Senator Aaron A. Sargent of California introduced to the Senate an amendment to the Constitution "Conferring upon Women the Right of Suffrage." Drafted by Susan B. Anthony, this same amendment would be introduced on a near-yearly basis until its final passage by Congress on May 19, 1919. Varying degrees of voting rights presented an…

  9. Teaching Facial Expressions of Emotion

    ERIC Educational Resources Information Center

    Lierheimer, Kristin; Stichter, Janine

    2011-01-01

    Many students with exceptionalities, such as Aaron, display challenging behaviors that have a substantial impact on their quality of life and greatly disrupt the educational process (Matson, Wilkins, & Macken, 2009; Westling, 2010). Challenging behavior often causes academic and social difficulties for the students displaying the behavior,…

  10. 78 FR 51170 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ...://www.regulations.gov . Follow the instructions for submitting comments. Mail: Federal Docket Management... Reduction Agency 8725 John J Kingman Rd Stop 6201, Fort Belvoir, VA 22060-6201 Reach Back Software... natural or man-made effects/events. Dated: August 14, 2013. Aaron Siegel, Alternate OSD Federal...

  11. 76 FR 22716 - Center for Scientific Review; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-22

    ... Institutes of Health 6701 Rockledge Drive, Bethesda, MD 20892. (Virtual Meeting.) Contact Person: Aaron..., Bethesda, MD 20892. (Virtual Meeting.) Contact Person: John Bleasdale, PhD, Scientific Review Officer...: National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892. (Virtual Meeting.) Contact...

  12. 77 FR 19281 - Environmental Impacts Statements; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ..., Rogue River-Siskiyou National Forest, Coos County, OR, Comment Period Ends: 05/14/2012, Contact: Wesley... in Plaquemines Parish, LA, Review Period Ends: 04/30/2012, Contact: Dr. William P. Klein, Jr. 504-862..., Comment Period Ends: 04/10/2012, Contact: Dr. Aaron O. Allen 805- 585-2148. Revision to FR...

  13. Combined Heat & Power Using the Infinia Concentrated Solar CHP PowerDish System

    DTIC Science & Technology

    2013-08-01

    Executive Orders FOB - Forward Operating Base FPSE - Free Piston Stirling Engine GHG - Greenhouse Gas ICC - International Code Council IMA...Piston Stirling Generator 11 Figure 3: PowerDish CHP with Heat Exchanger 12 Figure 4: Infinia CHP PowerDish testing, Kennewick WA... Robert Kuykendahl Jason Modrell Aaron Erickson Vista Engineering Technologies 1355 Columbia Park Trail Richland, WA 99352 (509) 737

  14. 76 FR 17160 - Notice of Finding of No Significant Antitrust Changes and Time for Filing Requests for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... INFORMATION CONTACT: Aaron Szabo, Financial Analyst, Financial Analysis and International Projects Branch... Analysis and Recommendation In reaching this conclusion, the NRC staff considered the structure of the...'s analysis and recommendation, the Director of NRR has concluded in his decision dated March...

  15. Refractive Effects in Remote Sensing of the Atmosphere with Infrared Transmission Spectroscopy

    DTIC Science & Technology

    1975-06-01

    Snider Aaron Goldman June 1975 Approved for public release; distribution unlimited. USA BALLISTIC RESEARCH LABORATORIES ABERDEEN PROVING GROUND...of the Army position, unless so designated by other authorized documents. UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PACE (When Dete Entered...Command 5001 Kisenhower Avenue Alexandria, VA 22333 12. REPORT DATE .TUNE 1975 13. NUMBER OF PAGES 158 14. MONITORING AGENCY NAME 4

  16. Assessing and Changing Organizational Culture and Climate for Effective Services

    ERIC Educational Resources Information Center

    Glisson, Charles

    2007-01-01

    The 2007 Aaron Rosen Lecture was presented at the annual meeting of the Society for Social Work and Research, January 12, 2007, in San Francisco, CA. The lecture begins by describing the gap between what is known about efficacious treatments and other evidence-based practices on the one hand and the services that are provided in actual…

  17. Science, Social Work, Prevention: Finding the Intersections

    ERIC Educational Resources Information Center

    Hawkins, J. David

    2006-01-01

    Over the past 25 years the science of prevention of adolescent health and behavior problems has matured as a result of longitudinal studies of predictors of these problems and controlled studies of preventive interventions focused on those predictors that have revealed efficacious prevention strategies. This article builds on three Aaron Rosen…

  18. Teaching Matters: Observations on Teacher Evaluations

    ERIC Educational Resources Information Center

    Hibler, David W.; Snyder, Jeffrey Aaron

    2015-01-01

    In this essay, the authors reflect on the ongoing teacher effectiveness debate. W. David Hibler is an experienced language arts teacher, who has taught in public high schools and middle schools in Alaska, North Carolina, and New York City. Jeffrey Aaron Snyder is a historian of education who writes about schooling in the twentieth-century United…

  19. Overcoming Risk: An Annotated Bibliography of Publications Developed by ERIC Clearinghouses.

    ERIC Educational Resources Information Center

    Schwartz, Wendy, Ed.; Howley, Craig, Ed.

    This publication contains two essays and an annotated bibliography of publications about risk. The entries in the bibliography were produced by the various clearinghouses in the ERIC system. The first essay, "Who Is at Risk? Definitions, Demographics, and Decisions," by Aaron M. Pallas, categorizes personal, family, and environmental factors that…

  20. An Upstart Web Catalog Challenges an Academic-Library Giant

    ERIC Educational Resources Information Center

    Foster, Andrea L.

    2008-01-01

    21-year-old Aaron Swartz is attempting to turn the library world upside down. He is taking on the subscription-based WorldCat, the largest bibliographic database on the planet, by building a free online book catalog that anyone can update. Many academic librarians are wary of Mr. Swartz's project because it will allow nonlibrarians, who may be…

  1. Evaluating the Properties of the Evidence-Based Practice Attitude Scale (EBPAS) in Health Care

    ERIC Educational Resources Information Center

    Melas, Christos D.; Zampetakis, Leonidas A.; Dimopoulou, Anastasia; Moustakis, Vassilis

    2012-01-01

    The Evidence-Based Practice Attitude Scale (EBPAS; Aarons, 2004) is a relatively new construct for the study of attitudes toward the adoption of innovation and evidence-based practices (EBPs) in mental health service settings. Despite widespread interest in measuring the attitudes of health care providers in conjunction with the adoption of EBPs,…

  2. 77 FR 70161 - Meeting of the National Environmental Education Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-23

    ... the Council, form work groups and develop plans for the report to congress. This is an open meeting... Designated Federal Officer (DFO) at the number listed below to schedule agenda time. Time will be allotted on... disability, please request it 10 days prior to the meeting, to give EPA as much time as possible to...

  3. Aeromedical Lessons from the Space Shuttle Columbia Accident Investigation

    NASA Technical Reports Server (NTRS)

    Pool, Sam L.

    2005-01-01

    This paper presents the aeromedical lessons learned from the Space Shuttle Columbia Accident Investigation. The contents include: 1) Introduction and Mission Response Team (MRT); 2) Primary Disaster Field Office (DFO); 3) Mishap Investigation Team (MIT); 4) Kennedy Space Center (KSC) Mishap Response Plan; 5) Armed Forces Institute of Pathology (AFIP); and 6) STS-107 Crew Surgeon.

  4. 75 FR 57544 - Defense Trade Advisory Group; Notice of Open Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-21

    ... to the Department of State facilities is controlled, persons wishing to attend the meeting must... accommodation should notify the Alternate DFO by the same date. Each non-member observer or DTAG member that... individuals who enter Department facilities. The data will be entered into the Visitor Access Control...

  5. 76 FR 66775 - Defense Trade Advisory Group; Notice of Open Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    ... facilities is controlled, persons wishing to attend the meeting must notify the DTAG Alternate Designated... attend the plenary session. A person requesting reasonable accommodation should notify the Alternate DFO... the collection is to validate the identity of individuals who enter Department facilities. The...

  6. 78 FR 67436 - Defense Trade Advisory Group; Notice of Open Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... access to Department of State facilities is controlled, persons wishing to attend the meeting must notify... requesting reasonable accommodation should notify the Alternate DFO by the same date. Anyone who wishes to... who enter Department facilities. The data will be entered into the Visitor Access Control System...

  7. 78 FR 71022 - Defense Trade Advisory Group; Notice of Open Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-27

    ... of State facilities is controlled, persons wishing to attend the meeting must notify the ] DTAG... session. A person requesting reasonable accommodation should notify the Alternate DFO by the same date... identity of individuals who enter Department facilities. The data will be entered into the Visitor...

  8. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major.

    PubMed

    Farmaki, Kallistheni; Tzoumari, Ioanna; Pappa, Christina; Chouliaras, Giorgos; Berdoukas, Vasilios

    2010-02-01

    Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients' iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.

  9. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    PubMed

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  10. 75 FR 35001 - Blue Ribbon Commission on America's Nuclear Future, Reactor and Fuel Cycle Technologies Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ...: Department of Energy, Office of Nuclear Energy. ACTION: Notice of Open Meeting. SUMMARY: This notice... CommissionDFO@nuclear.energy.gov . Additional information may also be available at http://www.brc.gov... a.m. on July 12 with the presentations regarding the Department of Energy's Office of Nuclear...

  11. 75 FR 67958 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Doc No: 2010-27902] DEPARTMENT OF ENERGY Blue Ribbon Commission on America's Nuclear Future AGENCY: Office of Nuclear Energy, Department of Energy. ACTION: Notice of open meeting. SUMMARY: This notice... (202) 586-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov ....

  12. 76 FR 2891 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ... Ribbon Commission on America's Nuclear Future AGENCY: Office of Nuclear Energy, Department of Energy...-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional information... and nuclear waste. The Commission is scheduled to submit a draft report to the Secretary of Energy...

  13. 75 FR 35000 - Blue Ribbon Commission on America's Nuclear Future, Disposal Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... Ribbon Commission on America's Nuclear Future, Disposal Subcommittee AGENCY: Department of Energy, Office of Nuclear Energy. ACTION: Notice of Open Meeting. SUMMARY: This notice announces an open meeting of... (202) 586-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov ....

  14. 75 FR 51247 - Blue Ribbon Commission on America's Nuclear Future, Disposal Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... Ribbon Commission on America's Nuclear Future, Disposal Subcommittee AGENCY: Department of Energy, Office of Nuclear Energy. ACTION: Notice of open meeting. SUMMARY: This notice announces an open meeting of... (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional information will be available...

  15. 76 FR 1607 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... Ribbon Commission on America's Nuclear Future AGENCY: Department of Energy, Office of Nuclear Energy...) 586-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov . Additional.... Department of Energy, 1000 Independence Avenue, SW., Washington, DC 20585, e-mail to...

  16. 75 FR 10791 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Ribbon Commission on America's Nuclear Future AGENCY: Department of Energy, Office of Nuclear Energy...-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy.gov . SUPPLEMENTARY INFORMATION... knowledge of issues pertaining to nuclear energy. Purpose of the Meeting: Inform the Commission...

  17. 76 FR 1608 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... Ribbon Commission on America's Nuclear Future AGENCY: Department of Energy, Office of Nuclear Energy... and nuclear waste. The Commission is scheduled to submit a draft report to the Secretary of Energy by... to CommissionDFO@nuclear.energy.gov , or post comments on the Commission Web site at...

  18. 77 FR 14769 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... register to address the Panel. The Panel's DFO will have a ``Sign-Up Roster'' available at the Panel... further public comments will be accepted. Anyone who signs-up to address the Panel, but is unable to do so... Formulary. Meeting Agenda 1. Sign-In. 2. Welcome and Opening Remarks. 3. Public Citizen Comments....

  19. 75 FR 51984 - Federal Advisory Committee; Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... address the Panel. The Panel's DFO will have a ``Sign-Up Roster'' available at the Panel meeting, for... comments will be accepted. Anyone who signs up to address the Panel, but is unable to do so due to the time... regarding the Uniform Formulary. Meeting Agenda Sign-In; Welcome and Opening Remarks; Public...

  20. 78 FR 33074 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    .... The Panel's DFO will have a ``Sign-Up Roster'' available at the Panel meeting for registration on a... be accepted. Anyone who signs-up to address the Panel, but is unable to do so due to the time..., regarding the Uniform Formulary. Meeting Agenda 1. Sign-In 2. Welcome and Opening Remarks 3. Public...

  1. 76 FR 78620 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ...'s DFO will have a ``Sign-Up Roster'' available at the Panel meeting for registration on a first... accepted. Anyone who signs-up to address the Panel, but is unable to do so due to the time limitation, may... Agenda 1. Sign-In. 2. Welcome and Opening Remarks. 3. Public Citizen Comments. 4. Scheduled...

  2. 78 FR 74120 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    .... The Panel's DFO will have a ``Sign-Up Roster'' available at the Panel meeting for registration on a... be accepted. Anyone who signs-up to address the Panel, but is unable to do so due to the time... Pharmacy and Therapeutics Committee, regarding the Uniform Formulary. Meeting Agenda 1. Sign-In 2....

  3. 76 FR 28959 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... register to address the Panel. The Panel's DFO will have a ``Sign-Up Roster'' available at the Panel..., no further public comments will be accepted. Anyone who signs up to address the Panel, but is unable... Agenda: 1. Sign-In 2. Welcome and Opening Remarks 3. Public Citizen Comments 4. Scheduled...

  4. 76 FR 55381 - FIFRA Scientific Advisory Panel; Notice of Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    .... Special accommodations. For information on access or services for individuals with disabilities, and to request accommodation of a disability, please contact the DFO listed under FOR FURTHER INFORMATION CONTACT... accommodations. Submit nominations to serve as ad hoc members of FIFRA SAP, requests for special...

  5. 78 FR 56231 - Government-Wide Travel Advisory Committee (GTAC); Public Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... ADMINISTRATION Government-Wide Travel Advisory Committee (GTAC); Public Advisory Committee Meeting AGENCY: Office... Government-wide Travel Advisory Committee (GTAC) (the Committee), is a Federal Advisory Committee established... CONTACT: Ms. Marcerto Barr, Designated Federal Officer (DFO), Government-wide Travel Advisory...

  6. 77 FR 22316 - Notification of a Public Teleconference of the Science Advisory Board Ecological Processes and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Advisory Committee Act (FACA) (5 U.S.C. App. 2) and related regulations. Pursuant to FACA and EPA policy...: http://yosemite.epa.gov/sab/sabproduct.nsf/fedrgstr_activites/RAF%20Eco%20Action%20Plan?OpenDocument... minutes per speaker. Interested parties should contact Dr. Thomas Armitage, DFO, in writing...

  7. 46 CFR 46.10-60 - Control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Control. 46.10-60 Section 46.10-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES SUBDIVISION LOAD LINES FOR PASSENGER VESSELS Administration § 46.10-60 Control. The Director, Field Operations (DFO) or the Coast Guard District Commander...

  8. 46 CFR 46.10-60 - Control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Control. 46.10-60 Section 46.10-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES SUBDIVISION LOAD LINES FOR PASSENGER VESSELS Administration § 46.10-60 Control. The Director, Field Operations (DFO) or the Coast Guard District Commander...

  9. 46 CFR 42.07-60 - Control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Control. 42.07-60 Section 42.07-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND FOREIGN VOYAGES BY SEA Control, Enforcement, and Rights of Appeal § 42.07-60 Control. (a) The Director, Field Operations (DFO) or the...

  10. 46 CFR 42.07-60 - Control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Control. 42.07-60 Section 42.07-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND FOREIGN VOYAGES BY SEA Control, Enforcement, and Rights of Appeal § 42.07-60 Control. (a) The Director, Field Operations (DFO) or the...

  11. 46 CFR 42.07-60 - Control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Control. 42.07-60 Section 42.07-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND FOREIGN VOYAGES BY SEA Control, Enforcement, and Rights of Appeal § 42.07-60 Control. (a) The Director, Field Operations (DFO) or the...

  12. 46 CFR 46.10-60 - Control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Control. 46.10-60 Section 46.10-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES SUBDIVISION LOAD LINES FOR PASSENGER VESSELS Administration § 46.10-60 Control. The Director, Field Operations (DFO) or the Coast Guard District Commander...

  13. Investigation of biologically-designed metal-specific chelators for potential metal recovery and waste remediation applications.

    SciTech Connect

    Criscenti, Louise Jacqueline; Ockwig, Nathan W.

    2009-01-01

    Bacteria, algae and plants produce metal-specific chelators to capture required nutrient or toxic trace metals. Biological systems are thought to be very efficient, honed by evolutionary forces over time. Understanding the approaches used by living organisms to select for specific metals in the environment may lead to design of cheaper and more effective approaches for metal recovery and contaminant-metal remediation. In this study, the binding of a common siderophore, desferrioxamine B (DFO-B), to three aqueous metal cations, Fe(II), Fe(III), and UO{sub 2}(VI) was investigated using classical molecular dynamics. DFO-B has three acetohydroxamate groups and a terminal amine group that all deprotonate with increasing pH. For all three metals, complexes with DFO-B (-2) are the most stable and favored under alkaline conditions. Under more acidic conditions, the metal-DFO complexes involve chelation with both acetohydroxamate and acetylamine groups. The approach taken here allows for detailed investigation of metal binding to biologically-designed organic ligands.

  14. 76 FR 18586 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of The ACRS Subcommittee on United...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... Report (SER) associated with the US-APWR design certification as well as technical reports related to the Gas Turbine Generator design. The Subcommittee will hear presentations by and hold discussions with... website cited above or by contacting the identified DFO. Moreover, in view of the possibility that...

  15. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    PubMed Central

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  16. 77 FR 14006 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of.... Written statements should be sent to the Designated Federal Officer (DFO) at: United States...

  17. 76 FR 60816 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of... statements should be sent to the Designated Federal Officer (DFO) at: United States Military Academy,...

  18. 77 FR 58529 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of... statements should be sent to the Designated Federal Officer (DFO) at: United States Military Academy,...

  19. 78 FR 9730 - Boston Harbor Islands Advisory Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... National Park Service Boston Harbor Islands Advisory Council Meeting AGENCY: National Park Service... Islands Advisory Council. The agenda includes a presentation by Sally Snowman, 70th keeper of Boston Light... Jacobson, DFO, Boston Harbor Islands National Recreation Area, 408 Atlantic Avenue, Suite 228, Boston,...

  20. 76 FR 37794 - U.S. Air Force Academy Board of Visitors; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... Department of the Air Force U.S. Air Force Academy Board of Visitors; Notice of Meeting AGENCY: U.S. Air..., the United States Air Force Academy (USAFA) Board of Visitors (BoV) will meet in Harmon Hall, 2304... Designated Federal ] Officer (DFO) at the Air Force Pentagon address detailed below at any time. However,...

  1. 78 FR 60266 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of... statements should be sent to the Designated Federal Officer (DFO) at: United States Military Academy,...

  2. 78 FR 13030 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of... (DFO) at: United States Military Academy, Office of the Secretary of the General Staff (MASG),...

  3. 78 FR 15928 - Forestry Research Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... Time, Monday through Friday. SUPPLEMENTARY INFORMATION: Background In accordance with the provisions of... as necessary and at such times as designated by the Designated Federal Officer (DFO). No individual..., religion, sex, national origin, age, mental or physical handicap, marital status, or sexual...

  4. 76 FR 35891 - Meeting of the Local Government Advisory Committee and Small Community Advisory Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... their point of view. Also, written comments should be submitted electronically to Zampieri.Paula@epa.gov... CONTACT: Paula Zampieri, DFO for the Local Government Advisory Committee (LGAC) and Small Community Advisory Subcommittee (SCAS) at (202) 566-2496 or e-mail at Zampieri.Paula@epa.gov . INFORMATION...

  5. 76 FR 51364 - Notification of a Public Teleconference of the Science Advisory Board Panel for the Review of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... wishing further information regarding this teleconference meeting may contact Mr. Thomas Carpenter...) 565- 2098 or via e-mail carpenter.thomas@epa.gov . General information concerning the EPA Science... should contact Mr. Thomas Carpenter, DFO, in writing (preferably via e-mail), at the contact...

  6. Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin

    PubMed Central

    Yalcintepe, Leman; Halis, Emre

    2016-01-01

    Increased intracellular iron levels can both promote cell proliferation and death, as such; iron has a “two-sided effect” in the delicate balance of human health. Though the role of iron in the development of cancer remains unclear, investigations of iron chelators as anti-tumor agents have revealed promising results. Here, we investigated the influence of iron and desferrioxamine (DFO), the iron chelating agent on intracellular calcium in a human leukemia cell line, K562. Iron uptake is associated with increased reactive oxygen species (ROS) generation. Therefore, we showed that iron also caused dose-dependent ROS generation in K562 cells. The measurement of intracellular calcium was determined using Furo-2 with a fluorescence spectrophotometer. The iron delivery process to the cytoplasmic iron pool was examined by monitoring the fluorescence of cells loaded with calcein-acetoxymethyl. Our data showed that iron increased intracellular calcium, and this response was 8 times higher when cells were incubated with DFO. K562 cells with DFO caused a 3.5 times increase of intracellular calcium in the presence of doxorubicin (DOX). In conclusion, DFO induces intracellular calcium and increases their sensitivity to DOX, a chemotherapeutic agent. PMID:26773173

  7. Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease

    PubMed Central

    Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Arantes, Jerusa Marilda; Silva, Maisa; Pedrosa, Maria Lúcia; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; Araújo, Márcio Sobreira Silva; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2010-01-01

    Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite. PMID:20663295

  8. 76 FR 14372 - Glenn/Colusa County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... Willows, California. Agenda items covered include: (1) Introductions, (2) Approve Minutes, (3) RAC Admin...., Willows, CA 95988. Individuals who wish to speak or propose a project or agenda items contact Eduardo Olmedo, DFO, 825 N. Humboldt Ave., Willows, CA 95988 or Laurie Pearson, Glenn/Colusa RAC...

  9. 75 FR 8916 - Glenn/Colusa County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... Willows, California. Agenda items covered include: (1) Introductions, (2) Approve Minutes, (3) RAC Admin..., 825 N. Humboldt Ave., Willows, CA 95988. Individuals who wish to speak or propose agenda items send their names and proposals to Eduardo Olmedo, DFO, 825 N. Humboldt Ave., Willows, CA 95988. FOR...

  10. 75 FR 27287 - Glenn/Colusa County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... Willows, California. Agenda items covered include: (1) Introductions, (2) Approve Minutes, (3) RAC Admin... District Office, 825 N. Humboldt Ave., Willows, CA 95988. Individuals who wish to speak or propose agenda items send their names and proposals to Eduardo Olmedo, DFO, 825 N. Humboldt Ave., Willows, CA 95988...

  11. 75 FR 63436 - Glenn/Colusa County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... Willows, California. Agenda items covered include: (1) Introductions, (2) Approve Minutes, (3) RAC Admin... District Office, 825 N. Humboldt Ave., Willows, CA 95988. Individuals who wish to speak or propose agenda items send their names and proposals to Eduardo Olmedo, DFO, 825 N. Humboldt Ave., Willows, CA 95988...

  12. Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial.

    PubMed

    Maggio, Aurelio; Vitrano, Angela; Capra, Marcello; Cuccia, Liana; Gagliardotto, Francesco; Filosa, Aldo; Romeo, Maria Antonietta; Magnano, Carmelo; Caruso, Vincenzo; Argento, Crocetta; Gerardi, Calogera; Campisi, Saveria; Violi, Pietro; Malizia, Roberto; Cianciulli, Paolo; Rizzo, Michele; D'Ascola, Domenico Giuseppe; Quota, Alessandra; Prossomariti, Luciano; Fidone, Carmelo; Rigano, Paolo; Pepe, Alessia; D'Amico, Gennaro; Morabito, Alberto; Gluud, Christian

    2009-04-01

    A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these were randomized and underwent intention-to-treat analysis. The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP-DFO patients compared with DFP-alone patients (P = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0.3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP-DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs.

  13. Iron chelation therapy in thalassemia syndromes.

    PubMed

    Cianciulli, Paolo

    2009-12-29

    Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron) the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO) has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce complications, and improve survival and quality of life of transfused patients.

  14. Iron Chelation Therapy in Thalassemia Syndromes

    PubMed Central

    Cianciulli, Paolo

    2009-01-01

    Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron) the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO) has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce complications, and improve survival and quality of life of transfused patients. PMID:21415999

  15. 78 FR 59678 - Notification of Two Public Teleconferences of the Chartered Science Advisory Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ...: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The EPA Science Advisory Board (SAB) Staff... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION... Federal Officer (DFO), EPA Science Advisory Board Staff Office (1400R), U.S. Environmental...

  16. 76 FR 31308 - Board of Visitors, United States Military Academy (USMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... Department of the Army Board of Visitors, United States Military Academy (USMA) AGENCY: Department of the... advisory committee meeting will take place: 1. Name of Committee: United States Military Academy Board of.... Written statements should be sent to the Designated Federal Officer (DFO) at: United States...

  17. 77 FR 7115 - Committee on Adjudication

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... committee will meet via a virtual, online Web forum extending over a period of approximately six weeks... virtual, online Web forum extending over a period of approximately six weeks. See 41 CFR 102-3.140(e... Federal Officer (DFO) acting as forum moderator. This virtual meeting will enable the committee to...

  18. 78 FR 14538 - Notification of a Public Teleconference of the Clean Air Scientific Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-06

    ... wants further information concerning the CASAC's public teleconference may contact Dr. Holly Stallworth, Designated Federal Officer (DFO) via telephone at (202) 564-2073 or email at stallworth.holly@epa.gov... three minutes for public teleconferences. Interested parties should contact Dr. Holly Stallworth,...

  19. 75 FR 1381 - Science Advisory Board Staff Office; Notification of a Public Teleconference of the Clean Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... wants further information concerning the teleconference may contact Dr. Holly Stallworth, Designated...; or e-mail at stallworth.holly@epa.gov . General information concerning the CASAC can be found on the..., interested parties should notify Dr. Holly Stallworth, DFO, by e-mail no later than January 20,...

  20. Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice

    PubMed Central

    Guo, Chuang; Zhang, Yu-Xin; Wang, Tao; Zhong, Man-Li; Yang, Zhao-Hui; Hao, Li-Juan; Chai, Rui; Zhang, Shuai

    2015-01-01

    The widely recognized neuroprotective effect of iron chelators is contributed by their ability to prevent reactive oxygen species (ROS) generation via the Fenton reaction, which sequesters redox-active Fe. An additional neuroprotective mechanism of iron-chelating compounds is to regulate the transcriptional activator hypoxia-inducible factor 1α (HIF-1α). In the present study, we observed that intranasal administration of deferoxamine decreased beta-amyloid (Aβ) deposition and rescued synapse loss in the brain of Aβ precursor protein and presenilin-1 (APP/PS1) double transgenic mice. We found that deferoxamine (DFO) up-regulated HIF-1α mRNA expression and its protein level, and further induced the proteins that are encoded from HIF-1-adaptive genes, including transferrin receptor (TFR), divalent metal transporter 1 (DMT1), and brain-derived neurotrophic factor (BDNF). The effects of DFO on the induction and stabilization of HIF-1α were further confirmed in vitro. This was accompanied by a decrease of Fe in the CA3 region of the hippocampus. Western blotting studies revealed that DFO differentially enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. The results suggest that the DFO may up-regulate several HIF-1-dependent neuroprotective-adaptive genes in AD via activating P38/HIF-1α pathway, which may serve as important therapeutic targets to the disease. PMID:26082716

  1. Arctic Sovereignty Disputes: International Relations Theory in the High North

    DTIC Science & Technology

    2011-12-01

    ABBREVIATIONS ANWR Alaska National Wildlife Refuge CFSP Common Foreign and Security Policy DFO Canada’s Department of Fisheries and Oceans EEZ...Clinton vetoed the bill citing the ANWR sections as the reason.156 4. Military Force Military cooperation was the initial basis of the post World War II

  2. 78 FR 67205 - Advisory Committee on Reactor Safeguards; Procedures for Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    .... Comments should be in the possession of the DFO 5 days prior to the meeting to allow time for reproduction... the meeting. Copies may be obtained upon payment of appropriate reproduction charges. ACRS meeting.... When Subcommittee meetings are held at locations other than at NRC facilities, reproduction...

  3. 76 FR 8778 - Meeting of the Department of Justice's (DOJ's) National Motor Vehicle Title Information System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... Information System (NMVTIS) Federal Advisory Committee AGENCY: Office of Justice Programs (OJP), Justice... Title Information System (NMVTIS) Federal Advisory Committee to discuss the role of the NMVTIS Federal...) 305-1661. FOR FURTHER INFORMATION CONTACT: Alissa Huntoon, Designated Federal Official (DFO),...

  4. 75 FR 54871 - Science Advisory Board Staff Office; Notification of a Clean Air Scientific Advisory Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... AGENCY Science Advisory Board Staff Office; Notification of a Clean Air Scientific Advisory Committee...). ACTION: Notice. SUMMARY: The Environmental Protection Agency (EPA) Science Advisory Board (SAB) Staff... Officer (DFO), EPA Science Advisory Board (1400R), U.S. Environmental Protection Agency, 1200...

  5. 76 FR 9015 - Reschedule-Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-16

    ... of view. Also, written comments should be submitted electronically to eargle.frances@epa.gov . Please.../scas and can be obtained by written request to the DFO. FOR FURTHER INFORMATION CONTACT: Frances Eargle... e-mail at eargle.frances@epa.gov . Information On Services for Those with Disabilities:...

  6. 76 FR 16413 - Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ..., written comments should be submitted electronically to eargle.frances@epa.gov . Please contact the... obtained by written request to the DFO. FOR FURTHER INFORMATION CONTACT: Frances Eargle, the Designated....frances@epa.gov . Information on Services for Those With Disabilities: For information on access...

  7. 76 FR 68439 - Meeting of the Small Communities Advisory Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ....frances@epa.gov or contact Frances Eargle the Designated Federal Officer (DFO) at the number listed below... extended, if the number of requests for appearances require it. FOR FURTHER INFORMATION CONTACT: Frances....frances@epa.gov . Information on Services for those with Disabilities: For information on access...

  8. 76 FR 61101 - Reschedule-Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    .... Also, written comments should be submitted electronically to eargle.frances@epa.gov . Please contact.../ocir/scas and can be obtained by written request to the DFO. FOR FURTHER INFORMATION CONTACT: Frances...-3115 or e-mail at eargle.frances@epa.gov . Information on Services for Those With Disabilities:...

  9. 76 FR 6785 - Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ..., written comments should be submitted electronically to eargle.frances@epa.gov . Please contact the... written request to the DFO. ] FOR FURTHER INFORMATION CONTACT: Frances Eargle, the Designated Federal Officer for the Local Government Advisory Committee (LGAC) at (202) 564-3115 or e-mail at...

  10. 77 FR 62498 - Advisory Council on Dependents' Education; Meeting Cancellation Notice and Open Meeting Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-15

    ... Federal Officer (DFO) for the Advisory Council on Dependents' Education, Mr. Joel K. Hansen, 4800 Mark... of the Secretary Advisory Council on Dependents' Education; Meeting Cancellation Notice and Open Meeting Notice AGENCY: Department of Defense Education Activity (DoDEA), DoD. ACTION: Meeting...

  11. 77 FR 20834 - Merchant Mariner Medical Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... qualifications of operators of commercial vessels, medical examiner education, and medical research. The meeting... medical research. Agenda: Day 1 (1) Opening comments by Designated Federal Officer (DFO), Captain E. P... SECURITY Coast Guard Merchant Mariner Medical Advisory Committee AGENCY: Coast Guard, DHS. ACTION:...

  12. 76 FR 53924 - Merchant Mariner Medical Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... medical research. Agenda Day 1 (1) Opening comments by Designated Federal Officer (DFO), Captain E. P... SECURITY Coast Guard Merchant Mariner Medical Advisory Committee AGENCY: Coast Guard, DHS. ACTION: Notice of federal advisory committee meeting. SUMMARY: The Merchant Mariner Medical Advisory...

  13. 76 FR 44307 - National Climate Assessment and Development Advisory Committee (NCADAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... National Oceanic and Atmospheric Administration (NOAA) National Climate Assessment and Development Advisory... Atmospheric Administration (NOAA), Department of Commerce (DOC). ACTION: Notice of open meeting. SUMMARY: The... attend all or a portion of the meeting by contacting the NCADAC DFO ( Cynthia.Decker@noaa.gov ) by...

  14. 78 FR 58536 - Notification of a Public Meeting of the Science Advisory Board Panel for the Review of the EPA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... AGENCY Notification of a Public Meeting of the Science Advisory Board Panel for the Review of the EPA...: The EPA Science Advisory Board (SAB) Staff Office announces a public meeting of the SAB Panel to... Officer (DFO), EPA Science Advisory Board Staff Office (1400R), U.S. Environmental Protection Agency,...

  15. 78 FR 77122 - Environmental Laboratory Advisory Board (ELAB) Meeting Dates and Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    .... Lara P. Phelps, DFO, US EPA (E243-05), 109 T. W. Alexander Drive, Research Triangle Park, NC 27709 or emailed to phelps.lara@epa.gov . Members of the public are invited to listen to the teleconference calls... contact Lara P. Phelps at the number above. To request accommodation of a disability, please contact...

  16. Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs.

    PubMed

    Vlahakos, Demetrios; Arkadopoulos, Nikolaos; Kostopanagiotou, Georgia; Siasiakou, Sofia; Kaklamanis, Loukas; Degiannis, Dimitrios; Demonakou, Maria; Smyrniotis, Vassilios

    2012-04-01

    We have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. In the Group DFO (n=7), 150mg/kg of DFO dissolved in normal saline was continuously infused in animals undergoing hepatic devascularization and portacaval anastomosis. The control group (Group C, n=7) underwent the same surgical procedure and received the same volume of normal saline infusion. Animals were euthanized after 24h. Hematological, biochemical parameters, malondialdehyde (MDA), and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were determined from sera obtained at baseline, at 12h, and after euthanasia. Hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were used to evaluate necrosis and apoptosis, respectively, in kidney sections obtained after euthanasia. A rapid and substantial elevation (more than 100-fold) of serum IL-6 levels was observed in Group C reaching peak at the end of the experiment, associated with increased production of oxygen free radicals and lipid peroxidation (MDA 3.2±0.1nmol/mL at baseline and 5.5±0.9nmol/mL at the end of the experiment, P<0.05) and various manifestations of SIRS and multiple organ dysfunction (MOD), including elevation of high-sensitivity C-reactive protein, severe hypotension, leukocytosis, thrombocytopenia, hypoproteinemia, and increased serum levels of lactate dehydrogenase (fourfold), alkaline phosphatase (fourfold), alanine aminotransferase (14-fold), and ammonia (sevenfold). In sharp contrast, IL-6 production and lipid

  17. Objectives and Methods of Iron Chelation Therapy

    PubMed Central

    Hershko, C.; Abrahamov, A.; Konijn, A. M.; Breuer, W.; Cabantchik, I. Z.; Pootrakul, P.; Link, G.

    2003-01-01

    Recent developments in the understanding of the molecular control of iron homeostasis provided novel insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival. However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Within recent years more than one thousand candidate compounds have been screened in animal models. The most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and; bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance by decreasing the demand on tedious parenteral drug administration. Combined use of DFO

  18. Northward extension of Carolina slate belt stratigraphy and structure, South-Central Virginia: Results from geologic mapping

    USGS Publications Warehouse

    Hackley, P.C.; Peper, J.D.; Burton, W.C.; Horton, J.W.

    2007-01-01

    Geologic mapping in south-central Virginia demonstrates that the stratigraphy and structure of the Carolina slate belt extend northward across a steep thermal gradient into upper amphibolite-facies correlative gneiss and schist. The Neoproterozoic greenschist-facies Hyco, Aaron, and Virgilina Formations were traced northward from their type localities near Virgilina, Virginia, along a simple, upright, northeast-trending isoclinal syncline. This syncline is called the Dryburg syncline and is a northern extension of the more complex Virgilina synclinorium. Progressively higher-grade equivalents of the Hyco and Aaron Formations were mapped northward along the axial trace of the refolded and westwardly-overturned Dryburg syncline through the Keysville and Green Bay 7.5-minute quadrangles, and across the northern end of the Carolina slate belt as interpreted on previous geologic maps. Hyco rocks, including felsic metatuff, metawacke, and amphibolite, become gneisses upgrade with areas of local anatexis and the segregation of granitic melt into leucosomes with biotite selvages. Phyllite of the Aaron Formation becomes garnet-bearing mica schist. Aaron Formation rocks disconformably overlie the primarily felsic volcanic and volcaniclastic rocks of the Hyco Formation as evidenced by repeated truncation of internal contacts within the Hyco on both limbs of the Dryburg syncline at the Aaron-Hyco contact. East-northeast-trending isograds, defined successively by the first appearance of garnet, then kyanite ?? staurolite in sufficiently aluminous rocks, are superposed on the stratigraphic units and synclinal structure at moderate to high angles to strike. The textural distinction between gneisses and identifiable sedimentary structures occurs near the kyanite ?? staurolite-in isograd. Development of the steep thermal gradient and regional penetrative fabric is interpreted to result from emplacement of the Goochland terrane adjacent to the northern end of the slate belt during

  19. Staphylococcus aureus-Related Diabetic Osteomyelitis: Medical or Surgical Management? A French and Spanish Retrospective Cohort.

    PubMed

    Lesens, Olivier; Desbiez, Françoise; Theïs, Clément; Ferry, Tristant; Bensalem, Maryse; Laurichesse, Henri; Tauveron, Igor; Beytout, Jean; Aragón Sánchez, Javier

    2015-09-01

    Staphylococcus aureus is the main cause of diabetic foot osteomyelitis (DFO) and can be treated medically or by surgery. We investigated the outcome of consecutive patients with a diagnosis of S aureus DFO retrospectively in 4 hospitals according to the type of management, medical (including debridement at bedside) or surgical. The outcome was classified as either favorable or failure (relapse, impaired wound healing, or amputation). Seventy-four patients with S aureus DFO, including 26 with methicillin-resistant S aureus, were included with a mean duration of follow-up of 21 ± 1 months. As part of the initial treatment, 47% underwent bone surgery followed with a short course of antibiotic. Others were treated with antibiotic therapy alone with bedside debridement. The outcome was favorable for 84% of these patients, with similar rates in the surgical and medical groups (80% vs 87%, P > .05). Patients in the medical group were less frequently hospitalized (49% vs 94%, P < .001) and had a shorter length of hospital stay (17 ± 3 vs 50 ± 12 days, P = .004). Patients in the surgery group received a shorter course of antibiotic therapy (10 ± 2 vs 11 ± 1 weeks, P = .001) with fewer side effects (9% vs 33%, P = .01). The type of management was not associated with subsequent new episode of noncontiguous DFO, which developed in 32% of cases. In conclusion, except significant differences in duration of hospitalization and antibiotic therapy, medical and surgical management of S aureus DFO had similar outcomes with a cure rate >80%.

  20. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage.

    PubMed

    Tchetina, Elena V; Markova, Galina A; Poole, A Robin; Zukor, David J; Antoniou, John; Makarov, Sergey A; Kuzin, Aleksandr N

    2016-01-01

    This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1-50 μM). Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs. Gene expression studies employed real-time PCR and included AMPK analyses in PBMCs. In OA explants collagen cleavage was frequently downregulated by 10-50 μM DFO. PCR analysis of 7 OA patient cartilages revealed that 10 μM DFO suppressed expression of MMP-1, MMP-13, IL-1β, and TNFα and a marker of chondrocyte hypertrophy, COL10A1. No changes were observed in the expression of glycolysis-related genes. In contrast, expressions of genes associated with the mitochondrial Krebs cycle (TCA), AMPK, HIF1α, and COL2A1 were upregulated. AMPK gene expression was reduced in OA cartilage and increased in PBMCs from the same patients compared to healthy controls. Our studies demonstrate that DFO is capable of suppressing excessive collagenase-mediated type II collagen cleavage in OA cartilage and reversing phenotypic changes. The concomitant upregulation of proanabolic TCA-related gene expressions points to a potential for availability of energy generating substrates required for matrix repair by end-stage OA chondrocytes. This might normally be prevented by high whole-body energy requirements indicated by elevated AMPK expression in PBMCs of OA patients.

  1. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage

    PubMed Central

    Markova, Galina A.; Poole, A. Robin; Zukor, David J.; Antoniou, John; Makarov, Sergey A.; Kuzin, Aleksandr N.

    2016-01-01

    This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1–50 μM). Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs. Gene expression studies employed real-time PCR and included AMPK analyses in PBMCs. In OA explants collagen cleavage was frequently downregulated by 10–50 μM DFO. PCR analysis of 7 OA patient cartilages revealed that 10 μM DFO suppressed expression of MMP-1, MMP-13, IL-1β, and TNFα and a marker of chondrocyte hypertrophy, COL10A1. No changes were observed in the expression of glycolysis-related genes. In contrast, expressions of genes associated with the mitochondrial Krebs cycle (TCA), AMPK, HIF1α, and COL2A1 were upregulated. AMPK gene expression was reduced in OA cartilage and increased in PBMCs from the same patients compared to healthy controls. Our studies demonstrate that DFO is capable of suppressing excessive collagenase-mediated type II collagen cleavage in OA cartilage and reversing phenotypic changes. The concomitant upregulation of proanabolic TCA-related gene expressions points to a potential for availability of energy generating substrates required for matrix repair by end-stage OA chondrocytes. This might normally be prevented by high whole-body energy requirements indicated by elevated AMPK expression in PBMCs of OA patients. PMID:28042296

  2. Evaluation and comparison of 1,2-indanedione and 1,8-diazafluoren-9-one solutions for the enhancement of latent fingerprints on porous surfaces.

    PubMed

    D'Elia, Valentina; Materazzi, Stefano; Iuliano, Gianpaolo; Niola, Luca

    2015-09-01

    1,2-indanedione (1,2-IND) and 1,8-diazafluoren-9-one (DFO) are used in the forensic field to enhance latent fingerprints deposited on porous surfaces due to the formation of fluorescent products by reacting with the amino acids present in the papillary exudate. The study was carried out in collaboration with the Fingerprints and Photography Section of the Carabinieri Scientific Investigation Department (RIS) of Rome, in which laboratories, until now, DFO has been the most used because of its excellent enhancing properties, even if it is more expensive and relatively toxic in comparison with the 1,2-IND. The aim of this work was then to evaluate and to compare the effectiveness of three solutions of 1,2-IND in different formulations and a DFO solution employed as single enhancing treatments, in order to assess whether it was possible to replace a reagent with the other obtaining equally satisfying results. In this case, white office paper was selected as deposit surface since it also permitted one to observe those reaction products that appear visible to a naked eye. Beside to a qualitative study of the visual characteristic of the enhanced fingerprints, further quantitative studies were conducted on the intensity of fluorescence of the products and on the consumption of amino acids during the reaction. The analyses, which at first were conducted on standard samples, were then repeated on real samples to validate the results obtained. The DFO confirmed its excellent enhancement properties, but also one of the three solutions of 1,2-IND showed comparable properties in terms of enhanced fingerprint definition and stability over time from the completion of a crime. As a result, we proved that a selected 1,2-IND formulation may replace with satisfactory achievements the DFO solution currently employed, providing also advantages from the point of view of safety and cost savings.

  3. Design of long circulating nontoxic dendritic polymers for the removal of iron in vivo.

    PubMed

    Imran ul-haq, Muhammad; Hamilton, Jasmine L; Lai, Benjamin F L; Shenoi, Rajesh A; Horte, Sonja; Constantinescu, Iren; Leitch, Heather A; Kizhakkedathu, Jayachandran N

    2013-12-23

    Patients requiring chronic red blood cell (RBC) transfusions for inherited or acquired anemias are at risk of developing transfusional iron overload, which may impact negatively on organ function and survival. Current iron chelators are suboptimal due to the inconvenient mode of administration and/or side effects. Herein, we report a strategy to engineer low molecular weight iron chelators with long circulation lifetime for the removal of excess iron in vivo using a multifunctional dendritic nanopolymer scaffold. Desferoxamine (DFO) was conjugated to hyperbranched polyglycerol (HPG) and the plasma half-life (t1/2) in mice is defined by the structural features of the scaffold. There was a 484 fold increase in t1/2 between the DFO (5 min) versus the HPG-DFO (44 h). In an iron overloaded mouse model, efficient iron excretion by HPG-DFO in the urine and feces was demonstrated (p = 0.0002 and 0.003, respectively) as was a reduction in liver, heart, kidney, and pancreas iron content, and plasma ferritin level (p = 0.003, 0.001, 0.001, 0.001, and 0.003, respectively) compared to DFO. Conjugates showed no apparent toxicity in several analyses including body weight, serum lactate dehydrogenase level, necropsy analysis, and by histopathological examination of organs. These findings were supported by in vitro biocompatibility analyses, including blood coagulation, platelet activation, complement activation, red blood cell aggregation, hemolysis, and cell viability. This nanopolymer-based chelating system would potentially benefit patients suffering from transfusional iron overload.

  4. Imaging of hepatocellular carcinoma patient-derived xenografts using 89Zr-labeled anti-glypican-3 monoclonal antibody

    PubMed Central

    Yang, Xiaoyang; Liu, Hongguang; Sun, Chris K.; Natarajan, Arutselvan; Hu, Xiang; Wang, Xiaolin; Allegretta, Mark; Guttmann, Ronald D.; Gambhir, Sanjiv S.; Chua, Mei-Sze; Cheng, Zhen; So, Samuel K.

    2015-01-01

    Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor prognosis. The membrane protein glypican-3 (GPC3) is a potential molecular target for early HCC detection as it is over-expressed in >50% of HCCs, and is associated with early hepatocarcinogenesis. We synthesized the positron emission tomography (PET) probe 89Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with 89Zr, and evaluated its tumor-targeting capacity. In vitro, 89Zr-DFO-1G12 was specifically taken up into GPC3-positive HCC cells only, but not in the GPC3-negative prostate cancer cell line (PC3). In vivo, 89Zr-DFO-1G12 specifically accumulated in subcutaneous GPC3-positive HCC xenografts only, but not in PC3 xenografts. Importantly, 89Zr-DFO-1G12 delineated orthotopic HCC xenografts from surrounding normal liver, with tumor/liver (T/L) ratios of 6.65 ± 1.33 for HepG2, and 4.29 ± 0.52 for Hep3B xenografts. It also delineated orthotopic xenografts derived from three GPC3-positive HCC patient specimens, with T/L ratios of 4.21 ± 0.64, 2.78 ± 0.26, and 2.31 ± 0.38 at 168 h p.i. Thus, 89Zr-DFO-1G12 is a highly translatable probe for the specific and high contrast imaging of GPC3-positive HCCs, which may aid early detection of HCC to allow timely intervention. PMID:24836949

  5. Dissolution Kinetics of Arsenopyrite in the Presence of Iron(III)-Sequestering Biogenic Ligands at pH 5.

    NASA Astrophysics Data System (ADS)

    Cornejo-Garrido, H.; Fernandez-Lomelin, P.; Guzman-Mendoza, J.; Sedov, S.; Cervini-Silva, J.

    2007-05-01

    Arsenopyrite is one of the most important natural sources of Arsenic on Earth. Arsenopyrite is relatively insoluble in pure water. That is not the case if it is exposed to environmental conditions. Notably, arsenopyrite surfaces exposed to biological activity undergo changes in lattice energy, surface morphology, particle size, and other properties, typical of mineral dissolution. Iron biogeochemical cycling is pivotal to electron transferring in nature. Therein, the need to further scrutinize on the mechanism of arsenopyrite dissolution induced by biological activity. In oxic environments, such as highly weathered soils or surficial seawater, microorganisms and higher plants produce biogenic ligands such as siderophores to mobilize Fe that otherwise would be unavailable. Siderophores ligands facilitate the dissolution of natural particles that represent a primary reservoir of iron. In this paper we study the stability of arsenopyrite in the presence of desferrioxamine (DFO-B), a common siderophore ligand, at pH 5. Arsenopyrite specimens from mines from Panasqueira, Portugal, were used for this study. Batch dissolution experiments of arsenopyrite (1 g L-1) in the presence of DFO-B ([DFO-B]0 - 200 ?M) were conducted for 7 days. The initial pH was adjusted to 5. Samples were stirred at 150 rpm. Sieving was conducted to homogeneized the particle size 0.149-0.1mm before conducting the dissolution experiments. Corresponding experiments in the absence of DFO-B for the purpose of comparison were also conducted. Analyses for soluble metals were conducted by AA and ICP-AES. Surface characterization was conducted by XRD and SEM-EDX. Incrustations of Pb(0) were detected in the arsenopyrite samples used for this study. In the presence of DFO-B, releases of Fe, As, and Pb showed positive trends with time. A shallower dependency was observed for release of Fe, As, and Pb in the presence of water only under similar experimental conditions. Detected concentrations of Fe, As, and

  6. Organization of motor pools supplying the cervical musculature in a cryptodyran turtle, Pseudemys scripta elegans. II. Medial motor nucleus and muscles supplied by two motor nuclei.

    PubMed

    Yeow, M B; Peterson, E H

    1986-01-08

    In this paper we describe the medial motor nucleus of Pseudemys cervical spinal cord and the motor pools of three neck muscles that exhibit an unusual pattern of innervation. Cells of the medial motor nucleus form a longitudinal column at the dorsomedial gray/white border of the ventral horn from C1 through C8. In Nissl-stained transverse sections they appear fusiform with prominent medially projecting dendrites; in HRP material these dendrites are seen to cross into the contralateral ventral funiculus. Medial nuclear cells vary in size (12-31 micron in diameter) and are often relatively large (greater than 21 micron in diameter). They are significantly larger and more numerous in caudal than in rostral cervical segments. Medial nuclear cells supply three of the cervical muscles examined in this study: mm. retrahens capitis collique (RCCQ), testocervicis, and longus colli. These three muscles differ from other cervical muscles in Pseudemys and from vertebrate limb muscles in that they are supplied in parallel by two populations of motor neurons: the medial and ventral motor nuclei (cf. Yeow and Peterson, '86). Ventral nuclear cells supplying these three muscles are organized into a musculotopic pattern with m. testocervicis motor neurons most medial and m. RCCQ motor neurons lateral; in contrast, the location of medial nuclear motor neurons is invariant with respect to muscle position. HRP-positive medial nuclear cells are sometimes smaller (m. testocervicis) but more often are as large or larger (mm. RCCQ and longus colli) than ventral nuclear cells supplying the same muscles, thus suggesting that they supply extrafusal muscle fibers, perhaps different muscle unit types in the three muscles. Based on the morphology of medial nuclear cells and the probable actions of the muscles they innervate, we hypothesize that the medial motor nucleus may represent a discrete functional system for producing bilaterally synchronous muscle activation, and that this system is

  7. Mind, Machine, and Creativity: An Artist's Perspective.

    PubMed

    Sundararajan, Louise

    2014-06-01

    Harold Cohen is a renowned painter who has developed a computer program, AARON, to create art. While AARON has been hailed as one of the most creative AI programs, Cohen consistently rejects the claims of machine creativity. Questioning the possibility for AI to model human creativity, Cohen suggests in so many words that the human mind takes a different route to creativity, a route that privileges the relational, rather than the computational, dimension of cognition. This unique perspective on the tangled web of mind, machine, and creativity is explored by an application of three relational models of the mind to an analysis of Cohen's talks and writings, which are available on his website: www.aaronshome.com.

  8. Mind, Machine, and Creativity: An Artist's Perspective

    PubMed Central

    Sundararajan, Louise

    2014-01-01

    Harold Cohen is a renowned painter who has developed a computer program, AARON, to create art. While AARON has been hailed as one of the most creative AI programs, Cohen consistently rejects the claims of machine creativity. Questioning the possibility for AI to model human creativity, Cohen suggests in so many words that the human mind takes a different route to creativity, a route that privileges the relational, rather than the computational, dimension of cognition. This unique perspective on the tangled web of mind, machine, and creativity is explored by an application of three relational models of the mind to an analysis of Cohen's talks and writings, which are available on his website: www.aaronshome.com. PMID:25541564

  9. Enhancement of radiopharmaceutical excretion by chemical interventions

    SciTech Connect

    Oster, Z.H.; Som, P.; Brill, A.B.; Sacker, D.F.; Atkins, H.L.

    1982-01-01

    The goal was to find methods of decreasing the radiation dose after radionuclide studies, by giving a compound that will increase the rate of excretion of the radionuclide. Sprague - 1 Dawley rats were given Tc-99m pertechnetate, Ga-67 citrate or Tl-201 chloride intravenously followed at intervals of 1 to 24 hours by one of the following compounds: desferroxamine (DFO), 2,3-dimercapto-1-propanol (BAL), triethylene tetraamine hexaacetic acid (TETHA), stannous tartarate, bleomycin (BLEO), 2,3-dimercaptosuccinic acid (DMSA), diethylene-triaminepentaacetic acid (DTPA), DTPA+SnCl.2H/sub 2/O, dihydroxybenzoic acid (DHB), and ferric-cyanoferrate (IT)(Prussian blue, PB). All the agents except PB are chelators. Some of these agents enhance excretion through the urinary tract (DFO), while most are excreted through the bile. PB was shown to increase Cs excrection through the G.I. tract. (ACR)

  10. Desferrioxamine as immunomodulatory agent during microorganism infection.

    PubMed

    Williams, A; Meyer, D

    2009-01-01

    Southern Africa is burdened with Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (M.tuberculosis) infections as well as conditions of iron (Fe) overload. Highly Active Antiretroviral Therapy (HAART) is used to treat HIV-infection, many drugs exist for the treatment of tuberculosis (new solutions are also being sought because of the existence of multi drug resistant strains of M.tuberculosis) and Fe chelators are commonly used to treat Fe overload. Chelators have also been shown to inhibit the multiplication of numerous microorganisms and hence there are publications suggesting a role for chelators like desferrioxamine (DFO) in the dual treatment of microorganism infection and excess iron. Excess iron fuels pathogen survival which in turn lowers host cell functionality (manifested as altered proliferation, cytokine secretion, etc); withholding iron (via a chelator) reverses the process, even more so when the cells are chelated for longer periods of time. Chelation with DFO is reviewed here by commenting on its immunomodulatory effect.

  11. Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils

    PubMed Central

    Völlger, Lena; Akong-Moore, Kathryn; Cox, Linda; Goldmann, Oliver; Wang, Yanming; Schäfer, Simon T.; Naim, Hassan Y.; Nizet, Victor; von Köckritz-Blickwede, Maren

    2016-01-01

    Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone–DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity. PMID:27129288

  12. Dissolution of arsenopyrite (FeAsS) and galena (PbS) in the presence of desferrioxamine-B at pH 5

    NASA Astrophysics Data System (ADS)

    Cornejo-Garrido, Hilda; Fernández-Lomelín, Pilar; Guzmán, José; Cervini-Silva, Javiera

    2008-06-01

    Microorganisms and higher plants produce biogenic ligands, such as siderophores, to mobilize Fe that otherwise would be unavailable. In this paper, we study the stability of arsenopyrite (FeAsS), one of the most important natural sources of arsenic on Earth, in the presence of desferrioxamine (DFO-B), a common siderophore ligand, at pH 5. Arsenopyrite specimens from mines in Panasqueira, Portugal (100-149 μm) that contained incrustations of Pb, corresponding to elemental Pb as determined by scanning electron microscopy-electron diffraction spectroscopy (SEM-EDX), were used for this study. Batch dissolution experiments of arsenopyrite (1 g L-1) in the presence of 200 μM DFO-B at initial pH (pH0) 5 were conducted for 110 h. In the presence of DFO-B, release of Fe, As, and Pb showed positive trends with time; less dependency was observed for the release of Fe, As, and Pb in the presence of only water under similar experimental conditions. Detected concentrations of soluble Fe, As, and Pb in suspensions containing only water were found to be ca. 0.09 ± 0.004, 0.15 ± 0.003, and 0.01 ± 0.01 ppm, respectively. In contrast, concentrations of soluble Fe, As, and Pb in suspensions containing DFO-B were found to be 0.4 ± 0.006, 0.27 ± 0.009, and 0.14 ± 0.005 ppm, respectively. Notably, the effectiveness of DFO-B for releasing Pb was ca. 10 times higher than that for releasing Fe. These results cannot be accounted for by thermodynamic considerations, namely, by size-to-charge ratio considerations of metal complexation by DFO-B. As determined by SEM-EDX, elemental sample enrichment analysis supports the idea that the Fe-S subunit bond energy is limiting for Fe release. Likely, the mechanism(s) of dissolution for Pb incrustations is independent and occurs concurrently to that for Fe and As. Our results show that dissolution of arsenopyrite leads to precipitation of elemental sulfur, and is consistent with a non-enzymatic mineral dissolution pathway. Finally, speciation

  13. Bacterial cell wall products increases stabilization of HIF-1 alpha in an oligodendrocyte cell line preconditioned by cobalt chloride or desferrioxamine.

    PubMed

    Yao, Song-yi; Soutto, Mohammed; Sriram, Subramaniam

    2008-08-30

    We examined the effect of lipopolysaccharide (LPS) or lipotechoic acid (LTA) on the regulation of hypoxia inducible factor (HIF-1) alpha on the MO3.13 cells, a human oligodendroglial cell line. Our study shows that MO3.13 cells express the toll like receptors (TLR's) but do not increase cellular levels of HIF-1 alpha following exposure to bacterial cell wall products. When MO3.13 cells were preconditioned by desferrioxamine (DFO) or cobalt chloride (CoCl(2)) and then treated with either LPS or LTA, HIF-1 alpha levels were higher than that induced by DFO or CoCl(2) alone. The increase in HIF-1 alpha was due to increased protein stability that was mediated by activation of the ERK-MAP kinase pathway.

  14. Adaptive Hydraulics/Hydrology (AdH) Pilot Point Specification: Guidelines for Solving 3D Groundwater Problems Utilizing Pilot Points

    DTIC Science & Technology

    2013-11-01

    Development Center (ERDC), Vicksburg, MS, under the general supervision of Dr. Aaron R . Byrd, P.E., Chief, HFH; Dr. Ty V. Wamsley, Chief, HF; and...José E. Sánchez, P.E., Acting Director, CHL. Supervision was provided by Stacy E. Howington, Principle Investigator, GEOTACS, and Joshua Fairley , Work...Package Manager, GEOTACS. COL Jeffrey R . Eckstein was the Commander and Executive Director of ERDC, and Dr. Jeffery P. Holland was the Director

  15. Growing Strategic Thinkers for the Air National Guard

    DTIC Science & Technology

    2010-06-03

    or culture and are self-governing standards designed to determine what acceptable and unacceptable conduct is. Therefore, to think ethically means to...fabric of all cultures , for the strategist they take on a more poignant dimension than simply understanding the difference between right and wrong; they...Bethel, Aaron Prupas, Tomislav Z. Ruby, and Michael V. Smith, “Developing Air Force Strategists: Change Culture , Reverse Careerism,” Joint

  16. U.S. Global Defense Posture, 1783-2011

    DTIC Science & Technology

    2012-01-01

    AND TRANSPORTATION INTERNATIONAL AFFAIRS LAW AND BUSINESS NATIONAL SECURITY POPULATION AND AGING PUBLIC SAFETY SCIENCE AND TECHNOLOGY TERRORISM...today. Third , World War II prompted an enduring shift in the preferred strategy of U.S. officials to one of defense in depth. A consensus formed... Paul Selva, Maj Gen James Holmes, Col David Fahrenkrug, Col Mark Burns, Lee Alloway, Fernando Manrique, Maj Aaron Clark, Group Captain Dean Andrew

  17. Difference Finite Durations of Anticoagulation and Outcomes Following Idiopathic Venous Thromboembolism: A Meta-Analysis

    DTIC Science & Technology

    2010-01-01

    screen for cancer or thrombophilia at enrollment, these conditions were occasionally diagnosed and reported during study follow-up. The patients...diagnosed with cancer or thrombophilia during follow-up were not excluded. Two authors (Christopher King and Aaron B. Hol- ley) independently selected...PE, enrolled after 3 mos No cancer/ thrombophilia screening INR 2-3 (83%) New cancer 11 patients 3, 6, 12 after randomization, then q6 84.8% Agnelli et

  18. CMMI (Trademark) for Development, Version 1.2

    DTIC Science & Technology

    2006-08-01

    organization’s training curriculum . CMMI for Development Version 1.2 Organizational Training (OT) 283 Examples of the information provided in the...or external), and skills needed include the following: • Subject-matter experts • Curriculum designers • Instructional designers • Instructors...Martin) • Cattan, Denise (Spirula) • Clouse, Aaron (Raytheon) • Connell , Clifford (Raytheon) • Fisher, Jerry (Aerospace Corporation) • Hertneck

  19. Access and Use of Data Lead to Innovative Ways to Reduce Energy Consumption, Officials Say

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2014-06-01

    Aaron Woro was selling residential solar energy systems in 2006 and performing site surveys in the San Francisco Bay Area for individual rooftops that required precise measurements due to roof geometry and shade from trees. One day, while standing on the rooftop of a large home, balancing a tape measure in one hand and a shade tool in the other, he slipped and fell, crashing through tree branches and bushes that partially broke his fall.

  20. Medical Management: Process Analysis Study Report

    DTIC Science & Technology

    2011-10-28

    SG6H mark.lamb@us.af.mil 11. Torry Hook torry.hook@us.army.mil 12. Dr Jeffrey R Klein CIV USA WRAMC Jeffrey.klein@med.navy.mil 13. Aaron L Heinrichs...MEDCOM HQ, sonyo.graham@us.army.mil 26. Michael P. Griffin CIV USA MEDCOM HQ, michael.griffin1@us.army.mil 27. Melanie A. Prince 52 MDOS/CC USAFE

  1. A Bayesian Analysis of the Flood Frequency Hydrology Concept

    DTIC Science & Technology

    2016-02-01

    Concept by Brian E. Skahill, Alberto Viglione, and Aaron Byrd PURPOSE: The purpose of this document is to demonstrate a Bayesian analysis of the...flood frequency hydrology concept as a formal probabilistic-based means by which to coherently combine and also evaluate the worth of different types...and development. INTRODUCTION: Merz and Blöschl (2008a,b) proposed the concept of flood frequency hydrology, which emphasizes the importance of

  2. Semiconductor-Based Nanotechnology Applications

    DTIC Science & Technology

    2012-11-07

    ferromagnetism. Thin film structures using Co doped SnO2 were fabricated and studied their usefulness in device applications. NP of semiconducting oxides such...12. Synthesis and Characterization of ZnO Sol - gel Powders; Amanda R. Snyder**, Lytia A. Smith**, Theron R. Fereday**, Jerry D. Harris, Aaron Thurber...Chemical Society (San Francisco, California, March 21 - 25, 2010). 13. Growth and Characterization of ZnO Thin Films ; Theron Fereday**, Lytia Smith

  3. Technology Security Policy: From the Cold War to the New World Order

    DTIC Science & Technology

    1993-12-01

    Alic. Lemis M. Branscomb, Harvey Brooks, Ashton B. Carter, and Gerald L. Epstein, Beyond Spinoff: Military and Commercial Technologies in a Changing...97. Is Aaron Karp , "Controlling Weapons Proliferation: The Role of Export Controlw The Journal of Strategic Studies, March 1993, p. 24. 19 Balancing...The National Interest: U.S. National Security Export Controls and Global Economic Competition, op. cit., p. 98. 20 Karp , op. cit., p. 40. 21

  4. Shipboard Electrical System Modeling for Early-Stage Design Space Exploration

    DTIC Science & Technology

    2013-04-01

    Shipboard Electrical System Modeling for Early -Stage Design Space Exploration Aaron M. Cramer, Hanling Chen Department of Electrical and Computer...Department United States Naval Academy Annapolis, MD, USA Email: zivi@usna.edu Abstract—In early -stage design exploration, it has been found that...involved the use of linear programming to model the action of the power system [6]. In this approach, the mechanical dynamics associated with prime movers

  5. Design and Experimental Validation of a Simple Controller for a Multi-Segment Magnetic Crawler Robot

    DTIC Science & Technology

    2015-04-01

    Design and experimental validation of a simple controller for a multi-segment magnetic crawler robot Leah Kelley*a, Saam Ostovari**b, Aaron B...magnetic crawler robot has been designed for ship hull inspection. In its simplest version, passive linkages that provide two degrees of relative...motion connect front and rear driving modules, so the robot can twist and turn. This permits its navigation over surface discontinuities while

  6. NASA GSFC Science Symposium on Atomic and Molecular Physics

    NASA Technical Reports Server (NTRS)

    Bhatia, Anand K. (Editor)

    2007-01-01

    This document is the proceedings of a conference on atomic and molecular physics in honor of the retirements of Dr. Aaron Temkin and Dr. Richard Drachman. The conference contained discussions on electron, positron, atomic, and positronium physics, as well as a discussion on muon catalyzed fusion. This proceedings document also contains photographs taken at the symposium, as well as speeches and a short biography made in tribute to the retirees.

  7. The MOOC Moment and the End of Reform

    ERIC Educational Resources Information Center

    Bady, Aaron

    2013-01-01

    The Massive Open Online Courses (MOOC) phenomenon has happened very quickly and is also a shift in discourse. This article aims to slow things down and go through the last year or so with a bit more care than we're usually able to do in order to do a "close reading" of the year of the MOOC. Author Aaron Brady ventures an opinion to say…

  8. Improving the Timeliness of Equal Employment Opportunity Complaint Processing in Department of Defense

    DTIC Science & Technology

    2015-01-01

    Improving the Timeliness of Equal Employment Opportunity Complaint Processing in Department of Defense Miriam Matthews, Nelson Lim C O R P O R A...trademark. Cover image: Stopwatch closeup, Fotolia@Aaron Amat; Seal, courtesy of DoD iii Preface The Offices of Diversity Management and Equal ...Opportunity and Civilian Personnel Policy aim to provide a work environment in which all Department of Defense (DoD) employees are provided equal

  9. Purchase of Microwave Reactors for Implementation of Small-scale Microwave-accelerated Organic Chemistry Laboratory Program in Undergraduate Curriculum and Synthetic Chemistry Research at HU

    DTIC Science & Technology

    2015-05-16

    Reactions Demonstrating Solvent and Organocatalyst Recyclability Jason M. Stacey, Andrew P. Dicks, Aaron A. Goodwin, Brittney M. Rush, and Manisha Nigam...MICROBAR! Discard the methylene chloride rinse into the chlorinated waste bottle . After you have prepared an NMR sample of your product and carried...DO NOT LOSE THE MICROBAR! Discard the methylene chloride rinse into the chlorinated waste bottle . After you have prepared an NMR sample of your

  10. Locking a Rubidium Oscillator to a Remote Time Scale Using Real-Time Common-View GPS Measurements

    DTIC Science & Technology

    2008-12-01

    CO 80305, USA lombardi@nist.gov LTjg. Aaron P. Dahlen Loran Support Unit United States Coast Guard (USCG) Wildwood, NJ 08260, USA...mechanism [7]. Its purpose is to correct the error, e , between a measured process variable (PV) and a desired set point (SP). The PID controller...proportional output, Kp is the proportional gain (a tuning parameter), e is the error (calculated as SP – PV), and t is the time of the current

  11. OIT Times Newsletter: Volume 3, Number 1, Winter 2000

    SciTech Connect

    Sousa, L.

    1999-12-16

    The Winter 2000 edition of the OIT Times newsletter, a quarterly publication produced by the Office of Industrial Technologies, highlights the 1999 start-up projects, announces the OIT solicitation schedule for FY2000, and features the success of the Ohio diecasting showcase. One of the quarterly highlights was Secretary Richardson's presentation of a Certificate of Partnership to Malden Mills CEO Aaron Feuerstein at the dedication of the plant's new, advanced cogeneration system.

  12. The Role of Defense Budgets in Civil-Military Relations

    DTIC Science & Technology

    1992-04-01

    N. Capitol Street, NE Suite 710 Washington, DC 20002 (202) 408-1517 " are available for $10.00O insBud P CONTENTS I. Introduction 1 II. The Defense...Stanley Collender, Paul Robert Gehman Jr., Edward Kolodziej, Alice Maroni , Allen Schick and Aaron Wildavsky for their comments on the manuscript. A...Through this process, the military services express their For one discussion of civil-military relations in the United Slates, see Samuel P . Huntington

  13. Eastern Renewable Generation Integration Study: Redefining What’s Possible for Renewable Energy

    ScienceCinema

    Bloom, Aaron

    2016-07-12

    NREL project manager Aaron Bloom introduces NREL’s Eastern Renewable Generation Integration Study (ERGIS) and high-performance computing capabilities and new methodologies that allowed NREL to model operations of the Eastern Interconnection at unprecedented fidelity. ERGIS shows that the Eastern Interconnection can balance the variability and uncertainty of wind and solar photovoltaics at a 5-minute level, for one simulated year.

  14. Design and Testing of a 30-Degree Sweep Laminar Flow Wing for a High-Altitude Long-Endurance Aircraft

    DTIC Science & Technology

    2004-10-01

    Center Room 342 Mechanical and Aerospace Engineering, Box 87-6106 Tempe, Arizona 85287-6106 USA Email: william.solomon@ngc.com /aaron.drake@ngc.com...wing laminar flow, which is the focus of this paper. 1.2 General Relationships Between Instability Mechanisms and Wing Sweep Angles Boundary-layer...transition in 3-D flows is a complicated process involving complex flow structures, multiple instability mechanisms , and nonlinear interactions. Four

  15. Fall 2014 SEI Research Review: Malware Distribution Networks

    DTIC Science & Technology

    2014-10-01

    University Pittsburgh, PA 15213 Team: Dr. Jose A. Morales Dr. William Casey Aaron Volkmann ( presenting ) Report Documentation Page Form...Research Review Presenter Last Name and Date © 2014 Carnegie Mellon University Copyright 2014 Carnegie Mellon University This material is based...Institute at permission@sei.cmu.edu. DM-0001740 3 Fall 2014 SEI Research Review Presenter Last Name and Date © 2014 Carnegie Mellon University

  16. Mixing of Liquid Cryogens in the Simulation of Liquid Hydrogen/Liquid Oxygen Explosion Hazards

    DTIC Science & Technology

    1990-08-01

    properties of all of the fluids used in the experiments are listed in Table 1. More information caa cryogenic fluid properties can be found in Barron 161...MIXING OF LIQUID CRYOGENS IN THE SIMULATION OF LIQUID HYDROGEN/LIQUID OXYGEN EXPLOSION HAZARDS T.S. Luchik, K.M. Aaron, E.Y. Kwack, P. Shakkottai...planetary missions at the Jet Propulsion Laboratory (JPL) use Radioisotope Thermoelectric Generators (RTGs) as part of the spacecraft’s power system

  17. Pattern-Theoretic Foundations of Automatic Target Recognition in Clutter

    DTIC Science & Technology

    2006-11-30

    area has continued past the September 2006 end date via discretionary funds provided to Aaron Lanterman through the Demetrius T. Paris Junior...support to continue the work past August 2006 provided by the Demetrius T. Paris Professorship. Pri- mary developer of ATR theory and algorithms for target...Oustanding Junior Teacher Award (2006), as voted on by the senior class. A.D. Lanterman, named the Demetrius T. Paris Junior Professor beginning in

  18. A generalized resistance resource: faith. A nursing view.

    PubMed

    Encarnação, Paula; Oliveira, Clara C; Martins, Teresa

    2015-12-17

    Based on Aaron Antonovsky's salutogenic model, the authors of this article aim to analyze the term Faith as a Generalized Resistance Resource (GRR) of people's health and to delve the relevance of this construct to clinical practice in Nursing. The authors consider that, in order for nurses to intervene in the promotion of faith so as to bring health benefits to people, a solid educational training in this subject area is required by nursing students.

  19. AMAS Robotics Seminar Brief

    DTIC Science & Technology

    2011-07-19

    Unclassified Unclassified 19 July 2011 AMAS ROBOTICS SEMINAR BRIEF Aaron Hart, Product Integrator, RS JPO DISTRIBUTION STATEMENT A. Approved for...19-07-2011 to 19-07-2011 4. TITLE AND SUBTITLE robotics seminar brief 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES AMAS ROBOTICS SEMINAR BRIEF 14

  20. Medical Surveillance Monthly Report (MSMR). Volume 21, Number 12, December 2014

    DTIC Science & Technology

    2014-12-01

    2014 Volume 21 Number 12 P A G E 2 Development and implementation of a cohort review for latent tuberculosis infection Christopher L. Aaron, DO...James D. Mancuso, MD, MPH, DrPH P A G E 8 Brief report: number of tuberculosis tests and diagnoses of latent tuberculosis infection in active...incidence settings for tuberculosis (TB), health departments periodically review their cases of latent TB infection (LTBI). Th e objective of this

  1. Unified Research on Network-Based Hard/Soft Information Fusion

    DTIC Science & Technology

    2016-02-02

    08/28/2012 08/28/2012 08/31/2011 10/11/2011 10/11/2011 Received Paper Amir Shirkhodaie, Vinayak Elagovan, Aaron Rababaah. Acoustic Semantic Labeling...Symposium, Conference: Signal Processing, Sensor Fusion, and Target Recognition XXI. 23-APR-12, . : , Amjad Alkilani, Amir Shirkhodaie. A Survey on Acoustic ...USA. : , Amjad Alkilani, Amir Shirkhodaie. Acoustic events semantic detection, classification, and annotation for persistent surveillance applications

  2. Trust-based Anonymous Communication: Adversary Models and Routing Algorithms

    DTIC Science & Technology

    2011-10-01

    Trust-based Anonymous Communication: Adversary Models and Routing Algorithms Aaron Johnson ∗ Paul Syverson U.S. Naval Research Laboratory... anonymous communication, and in particular onion routing, although we expect the approach to apply more broadly. This paper provides two main...contributions. First, we present a novel model to consider the various security con- cerns for route selection in anonymity networks when users vary their trust

  3. Preventing Active Timing Attacks in Low-Latency Anonymous Communication [Extended Abstract

    DTIC Science & Technology

    2010-07-01

    Preventing Active Timing Attacks in Low-Latency Anonymous Communication [Extended Abstract] Joan Feigenbaum1?, Aaron Johnson2??, and Paul Syverson3...itd.nrl.navy.mil Abstract. Low-latency anonymous communication protocols in gen- eral, and the popular onion-routing protocol in particular, are broken...inserting delays and dropping messages. We present a protocol that provides anonymity against an active adver- sary by using a black-box padding scheme

  4. Security Analysis of Accountable Anonymous Group Communication in Dissent

    DTIC Science & Technology

    2013-01-31

    Yale University Department of Computer Science Security Analysis of Accountable Anonymous Group Communication in Dissent Ewa Syta Aaron Johnson Henry...00-00-2013 4. TITLE AND SUBTITLE Security Analysis of Accountable Anonymous Group Communication in Dissent 5a. CONTRACT NUMBER 5b. GRANT NUMBER...are difficult to protect against traffic analysis, and accountable voting protocols are unsuited to general anonymous messaging. DISSENT, originally

  5. Modern HF Communications.

    DTIC Science & Technology

    1983-05-01

    AD-A131 163 MODERN HF COUNICATIONS(U) ADVISORY GROUP FOR AEROSPACE RESEARCH AND DEVELOPMENT NEUILLY-SUR-SEINE (FRANCE) d AARONS ET AL. MAY 83 AGARD...NORTH ATLANTIC TREATY ORGANIZATION ADVISORY GROUP FOR AEROSPACE RESEARCH AND DEVELOPMENT (ORGANISATION DU TRAITE DE L’ATLANTIQUE NORD) AGARD Lecture...other NATO bodies and to member nation-, in connection with research aind development problems in the aerospace field: Plros iding assistance to

  6. Improved Procedures for Formulation and Execution of Operations and Maintenance Budgets for Logistic Resources.

    DTIC Science & Technology

    1979-09-01

    1 I John D. Morgan Norman B. Davis Aaron B. Fuller i 1September 1979 I I IDA INSTITUTE FOR DEFENSE ANALYSES COST ANALYSIS GROUP 400 Army-Navy Drive ...Congressionally approved resource line items they represent service desired changes to these distributions of resources other than changes made to comply with the...containing a few hundred thousand dollars. It was used in lieu of the term " line items" because there is a specific hardware connotation to line items

  7. Search and Determine Integrated Environment (SADIE) for Space Situational Awareness

    DTIC Science & Technology

    2012-09-01

    Sabol 1 , Alan Segerman 2 , Aaron Hoskins 2 , Bryan Little 1 , Paul W. Schumacher Jr. 1 , Shannon Coffey 2 1 Air Force Research Laboratory...Directed Energy Directorate; Kihei, HI 2 Naval Research Laboratory; Washington, DC ABSTRACT A new high performance computing software applications...package called the Search and Determine Integrated Environment (SADIE) is being jointly developed and refined by the Air Force and Naval Research

  8. Range-Depth Tracking of Sounds from a Single-Point Deployment by Exploiting the Deep-Water Sound Speed Minimum

    DTIC Science & Technology

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Range-Depth Tracking of Sounds from a Single-Point...Deployment by Exploiting the Deep-Water Sound Speed Minimum Aaron Thode Scripps Institution of Oceanography University of California San Diego phone...mammal sounds in range and depth from a single mooring or platform (e.g. glider), by exploiting the propagation effects of the deep-water sound

  9. Preventing Terrorist Bombings on United States Subway Systems

    DTIC Science & Technology

    2006-09-01

    Next Steps in the War on Terror, ed. David Aaron (Santa Monica: Rand, 2005), 21. 2 Jim Turner, America at Risk: Closing the Public Transportation...system, for instance, consists of over 2,220 linear miles in Philadelphia, Bucks, Chester, Delaware and Montgomery counties in Pennsylvania, as well as...Force Sponsored by the Council on Foreign Relations, Gary Hart and Warren B. Rudman, co-chairs, Stephen E . Flynn, project director (2002). 11 “Mr

  10. Medical Services: Preventive Dentistry

    DTIC Science & Technology

    2007-11-02

    hygienist b. DENTAC— dental activity c. DFO— dental fitness officer d. DODDS—Department of Defense Dependent Schools e. HSC—U.S. Army Health Services Command f...community health dental hygienist (CHDH) in implementing these programs. (3) Coordinate with the preventive medicine activity and post or installation...aspects of preven- tive dentistry and dental public health programs. j. The community health dental hygienist , where assigned, will assist the DFO as

  11. Endocrine, biotransformation, and oxidative stress responses in salmon hepatocytes exposed to chemically induced hypoxia and perfluorooctane sulfonamide (PFOSA), given singly or in combination.

    PubMed

    Olufsen, Marianne; Arukwe, Augustine

    2015-11-01

    The effects of hypoxia and perfluorooctane sulfonamide (PFOSA), given singly and also in combination on endocrine, biotransformation, and oxidative stress responses were investigated in primary culture of salmon hepatocytes. Hypoxia was induced chemically using cobalt chloride (CoCl2) or deferroxamine (DFO). Primary culture of salmon hepatocytes were exposed to either CoCl2 (150 μM) or DFO (100 μM), in the presence or absence of PFOSA at 0, 25, and 50 μM for 24 and 48 h. Changes in transcript levels were analyzed by quantitative (real-time) PCR using gene-specific primers. CYP, catalase, GST, and SOD activities were analyzed spectrophotometrically. The hif-1α mRNA was used to validate cellular hypoxic condition, showing significantly induced transcription after 48-h exposure to DFO and CoCl2. Our data show that transcript levels for endocrine (ERα, Vtg, and Zrp), biotransformation (cyp1a, cyp3a, gst, and udpgt), and oxidative stress responses (catalase (cat), glutathione peroxidase (gpx), and glutathione reductase (gr)) were differentially modulated by PFOSA and hypoxia alone, and these effects were dependent on the response parameters and time of exposure. In combined exposure scenarios, the observed effects were apparently hypoxia-dependent. However, the observed effects at transcript levels were not concomitant with those at functional protein levels, further emphasizing the potential differences that may exist between these biological levels. Biplot of principal component analysis (PCA) showed grouping of response variables after 48 h of exposure. The distribution of observations and variables indicate that PFOSA had little effect on most response variables, while clustering show a unique association between a given hypoxia condition (i.e., CoCl2 or DFO) in combination with PFOSA and transcripts, proteins, or enzyme activities.

  12. Fish oil supplementation attenuates changes in plasma lipids caused by dexamethasone treatment in rats.

    PubMed

    Barbosa, Amanda Marreiro; Francisco, Priscila de Cássia; Motta, Katia; Chagas, Thayz Rodrigues; Dos Santos, Cristiane; Rafacho, Alex; Nunes, Everson Araújo

    2016-04-01

    Dexamethasone is an anti-inflammatory glucocorticoid that may alter glucose and lipid homeostasis when administered in high doses or for long periods of time. Omega-3 fatty acids, present in fish oil (FO), can be used as potential modulators of intermediary glucose and lipid metabolism. Herein, we evaluate the effects of FO supplementation (1 g·kg(-1) body weight (BW)) on glucose and lipid metabolism in rats treated with dexamethasone (0.5 mg·kg(-1) BW) for 15 days. Adult male Wistar rats were distributed among 4 groups: control (saline, 1 mL·kg(-1) BW and mineral oil, 1 g·kg(-1) BW), DEX (dexamethasone and mineral oil), FO (fish oil and saline), and DFO (fish oil and dexamethasone). Dexamethasone and saline were administered intraperitoneally, and fish oil and mineral oil were administered by gavage. We evaluated functional and molecular parameters of lipid and glycemic profiles at 8 days and at the end of treatment. FO supplementation increased hepatic docosahexaenoic acid (DEX: 5.6% ± 0.7%; DFO: 10.5% ± 0.8%) and eicosapentaenoic acid (DEX: 0.3% ± 0.0%; DFO: 1.3% ± 0.1%) contents and attenuated the increase of plasma triacylglycerol, total cholesterol, and non-high-density lipoprotein cholesterol concentrations in DFO rats compared with DEX rats. These effects seem not to depend on hepatic expression of insulin receptor substrate 1, protein kinase B, peroxisome proliferator-activated receptor γ coactivator 1-α, and peroxisome proliferator-activated receptor γ. There was no effect of supplementation on body weight loss, fasting glycemia, and glucose tolerance in rats treated with dexamethasone. In conclusion, we show that FO supplementation for 15 days attenuates the dyslipidemia induced by dexamethasone treatment.

  13. Difficult situations managing diabetic foot. Evidences and personal views: is to operate on patients with diabetic foot osteomyelitis old-fashioned?

    PubMed

    Senneville, Eric; Nguyen, Sophie

    2014-12-01

    Both medical and surgical approaches have been shown to be effective in the treatment of patients with diabetic foot osteomyelitis (DFO). In patients with risk factors of bad outcome such as major bone destruction, concomitant acute infections requiring drainage, problems in limb perfusion, highly resistant bacteria, and contraindication for or patient refusal of prolonged antibiotic therapy, the choice of surgery does not require further discussion. On the contrary, modest changes of bone on imaging assessment and no limiting factors as described above make medical treatment an attractive option for patients with DFO provided the rules of antibiotic treatment of chronic osteomyelitis are respected. The key question may not be to oppose surgery and medical treatment but to identify patients who need surgery and those who do not. There is currently no classification or score system that may allow physician to decide whether medical or surgical approach is best adapted to a given patient, and so both experience and skill of the multidisciplinary team appear paramount for guiding the choice of the best adapted ("tailored") strategy in a given patient. In this regard, it would be interesting to compare surgical and medical approaches for DFO that apparently may benefit from one or another (ie, bone lesions seen on plain radiographs of the foot but without bone fragmentation or multiple sites of osteomyelitis, no contraindication to prolonged antibiotic therapy, and location of bone involvement that may allow conservative surgery). Given the current available data on the therapeutic options of DFO, it appears that surgery for those patients is obviously not an old-fashioned option.

  14. Beliefs about chelation among thalassemia patients

    PubMed Central

    2012-01-01

    Background Understanding patients’ views about medication is crucial to maximize adherence. Thalassemia is a congenital blood disorder requiring chronic blood transfusions and daily iron chelation therapy. Methods The Beliefs in Medicine Questionnaire (BMQ) was used to assess beliefs in chelation in thalassemia patients from North America and London in the Thalassemia Longitudinal Cohort (TLC) of the Thalassemia Clinical Research Network (TCRN). Chelation adherence was based on patient report of doses administered out of those prescribed in the last four weeks. Results Of 371 patients (ages 5-58y, mean 24y), 93% were transfused and 92% receiving chelation (26% deferoxamine (DFO; a slow subcutaneous infusion via portable pump), 63% oral, 11% combination). Patients expressed high “necessity” for transfusion (96%), DFO chelation (92%) and oral chelation (89%), with lower “concern” about treatment (48%, 39%, 19% respectively). Concern about oral chelation was significantly lower than that of DFO (p<0.001). Self-reported adherence to chelation was not associated with views about necessity or concerns, but negatively correlated with perceived sensitivity to DFO (Sensitive Soma scale; r=−0.23, p=0.01) and side effects of oral chelation (r=−0.14, p=0.04). High ferritin iron levels, potentially indicating lower adherence, were found in 41% of patients reporting low necessity of oral chelation compared to 24% reporting high necessity (p=0.048). Concerns about treatment were associated with lower quality of life and more symptoms of anxiety and depression. Conclusions Despite their requirement for multimodal therapy, thalassemia patients have positive views about medicine, more so than in other disease populations. Patients may benefit from education about the tolerability of chelation and strategies to effectively cope with side effects, both of which might be beneficial in lowering body iron burden. Clinicaltrials.gov identifier NCT00661804 PMID:23216870

  15. Protection against hydrogen peroxide-mediated cytotoxicity in Friedreich's ataxia fibroblasts using novel iron chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone class.

    PubMed

    Lim, C K; Kalinowski, D S; Richardson, D R

    2008-07-01

    Iron-loading diseases remain an important problem because of the toxicity of iron-catalyzed redox reactions. Iron loading occurs in the mitochondria of Friedreich's ataxia (FA) patients and may play a role in its pathogenesis. This suggests that iron chelation therapy could be useful. We developed previously the lipophilic iron chelators known as the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) ligands and identified 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH) as the most promising analog. Hence, this study assessed the efficacy of PCTH and other PCIH analogs compared with various chelators, including deferiprone and desferrioxamine (DFO). Age- and sex-matched control and FA fibroblasts were preincubated with iron chelators and subsequently challenged with 50 microM H2O2 for up to 24 h. The current study demonstrates an interesting structure-activity relationship among the closely related PCIH series of ligands, with only PCTH being highly effective at preventing H2O2-induced cytotoxicity. PCTH increased FA fibroblast cell viability by up to 70%, whereas DFO rescued viability by 1 to 5% only. Hence, PCTH, which was well tolerated by cells was far more effective than DFO at preventing oxidative stress. It is noteworthy that kinetic studies demonstrated PCTH to rapidly penetrate cells to induce 59Fe efflux, whereas DFO, PCIH, 2-pyridylcarboxaldehyde benzoyl hydrazone, and 2-pyridylcarboxaldehyde m-bromobenzoyl hydrazone were far slower, indicating it is the rate of chelator permeation that is crucial for protection against H2O2. In addition, PCTH was found to be as effective as or more effective than conventional radical scavengers or the antioxidant idebenone (which has undergone clinical trials) at protecting cells against H2O2-mediated cytotoxicity. These findings further indicate the potential of PCTH for treatment of iron overload.

  16. Deferasirox shows in vitro and in vivo antileukemic effects on murine leukemic cell lines regardless of iron status.

    PubMed

    Lee, Dae-Hyoung; Jang, Pil Sang; Chung, Nack Gyun; Cho, Bin; Jeong, Dae Chul; Kim, Hack Ki

    2013-06-01

    Numerous studies have shown the antiproliferative effect of iron chelating agents (ICAs), which have been used traditionally in patients with secondary iron overload (SIO). Because the in vivo model for these studies has been animals with normal iron status, the antileukemic effect of ICAs in the SIO condition has not been determined clearly. We investigated the in vitro and in vivo effects of ICAs in murine leukemic cell lines regarding the iron status. The viability of both EL4 cells and L1210 cells incubated with either deferoxamine (DFO) or deferasirox (DFX) decreased in a concentration-dependent manner. This effect was most prominent in L1210 cells treated with DFX. The viability of L1210 cells incubated with both ICAs did not change regardless of the presence of ferric chloride. The percentage of apoptosis in L1210 cells treated with DFO or DFX increased in a concentration-dependent manner; however, the expression of Fas showed no significant change. The non-SIO mice and SIO mice bearing L1210 cells showed longer survival than other groups when treated with DFX, whereas the SIO mice treated with DFO showed shorter survival than the control group. The tumor was significantly smaller in the SIO mice treated with DFX or DFO compared with the control group. The iron content of the liver or the tumor in SIO mice decreased after ICA treatment. This study indicates an antileukemic effect of DFX regardless of iron status and suggests that the use of DFX has a survival benefit for SIO leukemia murine model in terms of iron chelation and antileukemic therapy.

  17. Immune and neural status of thalassemic patients receiving deferiprone or combined deferiprone and deferoxamine chelation treatment.

    PubMed

    Tourkantoni, Natalie; Athanassiou-Metaxa, Miranda; Zafiriou, Dimitrios; Tzimouli, Vassiliki; Economou, Marina; Taparkou, Antonia; Perifanis, Vassilios; Kanakoudi-Tsakalidou, Florendia

    2008-01-01

    Deferiprone (L1), has previously been reported to be associated with immunological abnormalities in iron loaded thalassemia patients. However, other factors may also have similar effects such as the level of iron overload, chronic immuno-stimulation due to transfusions, splenectomy and deferoxamine (DFO). During chelation therapy with DFO, several complications have been reported, which were due to pharmacological activity and high dose toxicity with regard to both acoustic and visual effects, as well as peripheral nerve disorders that were measured by nerve conduction velocities. The immune and neural status of 44 beta-thalassemic patients, aged 10-30 years (mean 19.4 +/- 4.9), receiving L1 as a monotherapy (n = 21), or in combination with DFO (n = 23), has been followed for 2 years by monitoring the level of immunoglobulins (IgG, IgM, IgA), the level of T and B lymphocytes (CD4/CD8), the auto antibodies: anti nuclear (ANA), anti-double-stranded (anti-ds DNA), anti reticulin (anti-R1), anti-extra nuclear (anti-ENA), anti histone (anti-AHA), anti liver-kidney-muscle (anti-LKM), anti-smooth muscle (anti-SMA), anti-thyroid (anti-ATA), anti-mitochondrial (anti-AMA) antibodies and the C-reactive protein. The percentage of patients with disorders of the immune and nervous system concerned very few cases. None of our patients with pathological findings in their immunological or neurophysiological examinations presented any signs or symptoms of involvement of the immune or nervous system. Further advantages have been identified for the oral use of L1 and its combination with DFO, including synergistic efficacy and lower dosing with limited toxicity.

  18. Effect of chemical stabilizers of hypoxia-inducible factors on early lung development.

    PubMed

    Groenman, Freek A; Rutter, Martin; Wang, Jinxia; Caniggia, Isabella; Tibboel, Dick; Post, Martin

    2007-09-01

    Low oxygen stimulates pulmonary vascular development and airway branching and involves hypoxia-inducible factor (HIF). HIF is stable and initiates expression of angiogenic factors under hypoxia, whereas normoxia triggers hydroxylation of the HIF-1alpha subunit by prolyl hydroxylases (PHDs) and subsequent degradation. Herein, we investigated whether chemical stabilization of HIF-1alpha under normoxic (20% O(2)) conditions would stimulate vascular growth and branching morphogenesis in early lung explants. Tie2-LacZ (endothelial LacZ marker) mice were used for visualization of the vasculature. Embryonic day 11.5 (E11.5) lung buds were dissected and cultured in 20% O(2) in the absence or presence of cobalt chloride (CoCl(2), a hypoxia mimetic), dimethyloxalylglycine (DMOG; a nonspecific inhibitor of PHDs), or desferrioxamine (DFO; an iron chelator). Vascularization was assessed by X-gal staining, and terminal buds were counted. The fine vascular network surrounding the developing lung buds seen in control explants disappeared in CoCl(2)- and DFO-treated explants. Also, epithelial branching was reduced in the explants treated with CoCl(2) and DFO. In contrast, DMOG inhibited branching but stimulated vascularization. Both DFO and DMOG increased nuclear HIF-1alpha protein levels, whereas CoCl(2) had no effect. Since HIF-1alpha induces VEGF expression, the effect of SU-5416, a potent VEGF receptor (VEGFR) blocker, on early lung development was also investigated. Inhibition of VEGFR2 signaling in explants maintained under hypoxic (2% O(2)) conditions completely abolished vascularization and slightly decreased epithelial branching. Taken together, the data suggest that DMOG stabilization of HIF-1alpha during early development leads to a hypervascular lung and that airway branching proceeds without the vasculature, albeit at a slower rate.

  19. Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier.

    PubMed

    Tyagi, Priyanka; Kumar, Amit; Gupta, Dikshi; Singh, Harpal

    2017-01-01

    Deferoxamine iron chelator has a limited therapeutic index due to rapid clearance from blood and possesses dose-limiting toxicity. Therefore, an intravenous deferoxamine delivery system based on dialdehyde cellulose (DAC) polymer was developed and its efficacy and toxicity were tested in iron-overloaded animals. The amino groups of deferoxamine were conjugated to free aldehyde moieties of dialdehyde cellulose via Schiff base reaction to form dialdehyde cellulose-deferoxamine (DAC-DFO) conjugate and characterized by Fourier transform infrared spectrophotometer, scanning electron microscope, and X-ray diffraction. The toxicity of prepared formulation was analyzed by XTT cell viability assay and LD50 study in mice. The change in serum iron levels, after intravenous administration of formulation, was observed in iron-overloaded rats. The DAC-DFO conjugate was tagged with Tc-99m to study the blood kinetics and observe change in blood circulation time. DAC-DFO conjugate was dispersible in water at concentration ∼75 mg/ml. In vitro cytotoxicity assay and LD50 study in mice indicated significantly enhanced safety of covalently bound deferoxamine (at >1000 mg/kg body weight compared to free drug at ∼270 mg/kg dose). A preliminary scintigraphy imaging and blood clearance study, with technetium-99m, indicated prolonged circulation of conjugated DFO in rabbit blood. A single dose of formulation injected into iron overloaded animals was found to maintain the normal serum iron levels until 10 days. The polymeric conjugate was effective in maintaining normal serum iron levels until 10 days at a dose of 100 mg/kg body weight.

  20. FTIR study of protective action of deferoxamine and deferiprone on the kidney tissues of aluminum loaded mice

    NASA Astrophysics Data System (ADS)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

    2014-01-01

    The present study was designed to evaluate the FTIR spectra of the aluminum exposed kidney tissues and recovered by chelating agents DFO and DFP then showed significant alteration on the major biochemical constituents such as lipids, proteins and glycogen at molecular level. The significant increased in the peak area of glycogen from 0.006 ± 0.001 to 0.187 ± 0.032 may be the interruption of aluminum in the calcium metabolism and the reduced level of calcium. The peak area value of amide A significantly decreased from control (4.931 ± 1.446) to aluminum (1.234 ± 0.052), but improved by DFP and DFO + DFP from 2.658 ± 0.153 to 3.252 ± 0.070 respectively. Amide I and amide II peak area values also decreased from 1.690 ± 0.133 to 0.811 ± 0.192 and 1.158 ± 0.050 to 0.489 ± 0.047 but treated with DFP and DFO + DFP significantly improved. This result suggests an alteration in the protein profile. The absence of Olefinicdbnd CH stretching band, Cdbnd O stretching of triglycerides and ring breathing mode in the DNA bases in aluminum exposure kidney suggests an altered lipid levels. Treated with DFP and DFO + DFP mice were considerably increased in lipid peroxidative markers. Further, assessed the activities of enzymatic antioxidants and measured the levels of nonenzymatic antioxidants. Concentrations of trace elements were found by ICP-OES. Histopathology of chelating agents treated kidney showed reduced renal damage in aluminum induced mice. Thus, histopathological findings confirmed the biochemical observations of this study. This results demonstrated that FTIR spectroscopy can be successfully applied to toxicological and biotoxicology studies.

  1. Effect of vitamin C, deferoxamine, quercetin and rutin against tert-butyl hydroperoxide oxidative damage in human erythrocytes.

    PubMed

    Krukoski, Daniel Witchmichen; Comar, Samuel Ricardo; Claro, Ligia Maria; Leonart, Maria Suely Soares; do Nascimento, Aguinaldo José

    2009-06-01

    The mature human erythrocyte, when submitted to oxidative stress, can demonstrate depletion of reduced glutathione, oxidation of the hemoglobin molecule and aggregation of complexes of iron close to the membrane. These can produce abnormalities in the erythrocyte membrane and hemolysis. The aim of this work was to study the antioxidative action of vitamin C (vit. C), deferroxamine (DFO) and the flavonoids quercetin and rutin in normal human erythrocytes, submitted to in vitro oxidative stress induced by tert-butylhydroperoxide ((t)BHP). Venous blood was collected in citrate-phosphate-dextrose (CPD) solution, as anticoagulant, from healthy adult individuals after informed consent. The erythrocytes were resuspended in PBS to obtain 35% globular volume, and then submitted to the oxidative action of (t)BHP for up to 30 min, with or without previous incubation for 60 min with vit. C, DFO, quercetin and rutin. Decrease in the GSH concentration, G6-PD and GR activities, and increase in the methemoglobin and Heinz bodies (HB) formation, occurred with the increase in (t)BHP concentration. (t)BHP did not effect on the membrane proteins detected by SDS-PAGE. Quercetin, partially prevented the GSH decrease and the formation of HB, but did not prevent MetHb formation from oxidative damage by (t)BHP. Rutin, after (t)BHP induction, prevented the GSH decrease and the formation of HB. Vit. C, had no influence on the depletion of GSH, inhibited partially the metHb formation, and it protected GR, but not G6-PD from oxidative damage by (t)BHP. DFO partially inhibited the metHb formation and GSH decrease, but it did not protect GR and G6-PD from oxidative damage by (t)BHP. The results obtained suggest that vit. C, DFO and the flavonoids quercetin and rutin contribute to the decrease in the oxidative stress caused by (t)BHP.

  2. New insight into the influence of carob extract and gallic acid on hemin induced modulation of HT29 cell growth parameters.

    PubMed

    Klenow, Stefanie; Glei, Michael

    2009-09-01

    Red meat intake is associated with an increased risk of developing cancer. This is possibly related to the heme content of red meat. Plant derived polyphenols might protect from cancer development via their antioxidant activities. In this study, the impact of an aqueous extract of carob (CE) on hemin-modulated proliferation was investigated. CE, gallic acid (GA) and a known iron chelator (deferoxamine: DFO) significantly reduced the number of human colon cancer HT29 cells. CE and GA were more effective under serum-free conditions than in normal cell culture medium. These effects were abolished by addition of 1 microM hemin at low concentrations of CE and GA. At higher concentrations of CE and GA, both substances reduced cell number despite hemin supplementation. Effects of CE, GA and DFO on cell number could not be linked to iron chelation even though CE and DFO were capable of chelating iron. Furthermore, the effects of high CE concentration point to antioxidative effects other than iron chelation. However, a connection to a reduction of colorectal cancer risk due to consumption of meat with high heme content by CE could not be drawn, since the effective concentrations are beyond the physiologically relevant concentrations.

  3. An analysis of the relationship between bulk tank milk quality and wash water quality on dairy farms in Ontario, Canada.

    PubMed

    Perkins, N R; Kelton, D F; Hand, K J; MacNaughton, G; Berke, O; Leslie, K E

    2009-08-01

    The objective of this study was to identify regions at high risk for bacterial water or milk contamination, as well as risk factors associated with high bacteria counts in raw milk in Ontario, Canada. Between 2003 and 2004, the Dairy Farmers of Ontario (DFO) tested water samples from 5,421 farms in Ontario for the presence of Escherichia coli and coliforms. The water samples were collected as "point-of-use" samples, meaning that each sample was taken from a tap or water hose in the milk house as soon as the water was turned on. Routine, monthly raw milk bacterial counts were determined by DFO using BactoScan (Foss, Hillerød, Denmark). BactoScan data were retrieved from DFO for all of the farms with water test results. The prevalence of samples with E. coli and coliforms in water and elevated bacteria counts in raw milk was 13.6, 53.8, and 2.8%, respectively. The spatial analysis, using a scan statistic, revealed 1 coliform and 3 E. coli clusters of contaminated water, but no clusters of elevated milk bacteria counts in raw milk in southern Ontario. The coliform water contamination cluster was the largest, with a radius of approximately 200 km. Regression analysis indicated that risk factors associated with the occurrence of high levels of bacteria in raw milk were elevated average monthly somatic cell count, increased total milk production, cooler seasons of the year, and the presence of E. coli in wash water.

  4. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation.

    PubMed

    Oexle, H; Gnaiger, E; Weiss, G

    1999-11-10

    Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells.

  5. The Meniscus-Deficient Knee

    PubMed Central

    Rao, Allison J.; Erickson, Brandon J.; Cvetanovich, Gregory L.; Yanke, Adam B.; Bach, Bernard R.; Cole, Brian J.

    2015-01-01

    Meniscal tears are the most common knee injury, and partial meniscectomies are the most common orthopaedic surgical procedure. The injured meniscus has an impaired ability to distribute load and resist tibial translation. Partial or complete loss of the meniscus promotes early development of chondromalacia and osteoarthritis. The primary goal of treatment for meniscus-deficient knees is to provide symptomatic relief, ideally to delay advanced joint space narrowing, and ultimately, joint replacement. Surgical treatments, including meniscal allograft transplantation (MAT), high tibial osteotomy (HTO), and distal femoral osteotomy (DFO), are options that attempt to decrease the loads on the articular cartilage of the meniscus-deficient compartment by replacing meniscal tissue or altering joint alignment. Clinical and biomechanical studies have reported promising outcomes for MAT, HTO, and DFO in the postmeniscectomized knee. These procedures can be performed alone or in conjunction with ligament reconstruction or chondral procedures (reparative, restorative, or reconstructive) to optimize stability and longevity of the knee. Complications can include fracture, nonunion, patella baja, compartment syndrome, infection, and deep venous thrombosis. MAT, HTO, and DFO are effective options for young patients suffering from pain and functional limitations secondary to meniscal deficiency. PMID:26779547

  6. Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing

    PubMed Central

    Scott, Christopher; Bonner, James; Min, Danqing; Boughton, Philip; Stokes, Rebecca; Cha, Kuan Minn; Walters, Stacey N.; Maslowski, Kendle; Sierro, Frederic; Grey, Shane T.; Twigg, Stephen; McLennan, Susan

    2014-01-01

    Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing. PMID:24990649

  7. Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

    PubMed Central

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

  8. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

    2013-09-01

    Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

  9. Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing.

    PubMed

    Scott, Christopher; Bonner, James; Min, Danqing; Boughton, Philip; Stokes, Rebecca; Cha, Kuan Minn; Walters, Stacey N; Maslowski, Kendle; Sierro, Frederic; Grey, Shane T; Twigg, Stephen; McLennan, Susan; Gunton, Jenny E

    2014-08-15

    Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing.

  10. Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.

    PubMed

    Maggio, Aurelio; Filosa, Aldo; Vitrano, Angela; Aloj, Giuseppina; Kattamis, Antonis; Ceci, Adriana; Fucharoen, Suthat; Cianciulli, Paolo; Grady, Robert W; Prossomariti, Luciano; Porter, John B; Iacono, Angela; Cappellini, Maria Domenica; Bonifazi, Fedele; Cassarà, Filippo; Harmatz, Paul; Wood, John; Gluud, Christian

    2011-10-15

    The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.

  11. Stimulation of proliferation in the colorectal mucosa by gastrin precursors is blocked by desferrioxamine.

    PubMed

    Ferrand, Audrey; Lachal, Shamilah; Bramante, Gianni; Kovac, Suzana; Shulkes, Arthur; Baldwin, Graham S

    2010-07-01

    Precursors of the peptide hormone gastrin stimulate proliferation in the colorectal mucosa and promote the development of colorectal carcinoma. Gastrins bind two ferric ions selectively and with high affinity, and the biological activity of glycine-extended gastrin (Ggly) in vitro is dependent on the presence of ferric ions. The aim of the present study was to determine whether or not iron is required for biological activity of progastrin and Ggly in vivo. Rats that had undergone a colostomy were infused with Ggly, and proliferation was measured in the defunctioned rectal mucosa. Proliferation was also measured in the colonic mucosa of hGAS and MTI-Ggly mice, which, by definition, overexpress progastrin and Ggly, respectively. The requirement for iron was assessed by thrice-weekly injection of the chelating agent desferrioxamine (DFO). The proliferation index in the defunctioned rectal mucosa was significantly increased in the Ggly-infused rats, and the increase was significantly reduced after treatment with DFO. Treatment with DFO significantly reduced the crypt height and proliferation index in the colonic mucosa of hGAS and MTI-Ggly mice but had no effect on the same variables in wild-type mice. These observations are consistent with the hypothesis that the biological activity of progastrin and Ggly in vivo is dependent on the presence of ferric ions and further suggest that chelating agents may block the stimulatory effects of gastrin precursors in the development of colorectal carcinoma.

  12. Iron distribution and histopathological study of the effects of deferoxamine and deferiprone in the kidneys of iron overloaded β-thalassemic mice.

    PubMed

    Yatmark, Paranee; Morales, Noppawan Phumala; Chaisri, Urai; Wichaiyo, Surasak; Hemstapat, Warinkarn; Srichairatanakool, Somdet; Svasti, Saovaros; Fucharoen, Suthat

    2016-09-01

    Renal glomerular and tubular dysfunctions have been reported with high prevalence in β-thalassemia. Iron toxicity is implicated in the kidney damage, which may be reversed by iron chelation therapy. To mimic heavy iron overload and evaluate the efficacy of iron chelators in the patients, iron dextran (180mg iron/mouse) was intraperitoneally (i.p.) injected in heterozygous β-globin knockout mice ((muβth-3/+), BKO) and wild type mice (C57BL/6J, WT) over a period of 2 weeks, followed by daily i.p. injection of deferoxamine (DFO) or deferiprone (L1) for 1 week. In BKO mice, iron preferentially accumulated in the proximal tubule with a grading score of 0-1 and increased to grade 3 after iron loading. In contrast, iron mainly deposited in the glomerulus and interstitial space in iron overloaded WT mice. Increased levels of kidney lipid peroxidation, glomerular and medullar damage and fibrosis in iron overloaded mice were reversed by treatment with iron chelators. L1 showed higher efficacy than DFO in reduction of glomerular iron, which was supported by a significantly decreased the amount of glomerular damage. Notably, DFO and L1 demonstrated a distinct pattern of iron distribution in the proximal tubule of BKO mice. In conclusion, chelation therapy has beneficial effects in iron-overloaded kidneys. However, the defect of kidney iron metabolism in thalassemia may be a determining factor of the treatment outcome in individual patients.

  13. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats

    PubMed Central

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Sripetchwandee, Jirapas; Srichairatanakool, Somdet; Fucharoen, Suthat; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2016-01-01

    Background Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX)) or an antioxidant (N-acetyl cysteine (NAC)) with a combined DFP and NAC treatments on left ventricular (LV) function with iron overload has not been investigated. Methods and Findings Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group) for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day) or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function. Conclusions The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats. PMID:27428732

  14. Future chelation monotherapy and combination therapy strategies in thalassemia and other conditions. comparison of deferiprone, deferoxamine, ICL670, GT56-252, L1NAll and starch deferoxamine polymers.

    PubMed

    Kontoghiorghes, George J

    2006-01-01

    Deferiprone (L1), and appropriate combinations with deferoxamine (DFO), can be used effectively for the treatment of thalassemia and other transfusional iron loading conditions. A number of experimental iron chelators such as deferasirox or ICL670 or Exjade (4-(3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl)-benzoic acid), deferitrin (4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and starch DFO polymers, are under clinical evaluation. ICL670 is the most advanced in development and appears to be effective in reducing liver iron in some patients but is overall ineffective in causing negative iron balance. It is also suspected that it is not effective in cardiac iron removal. Combination therapies using L1, DFO and new iron chelating drugs may cause higher efficacy and lower toxicity by comparison to monotherapies. However, several limitations including the high cost of the new chelating drugs may not facilitate the availability of these new treatments to the vast majority of thalassemia patients, most of whom live in developing countries.

  15. Novel Bifunctional Cyclic Chelator for 89Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates

    PubMed Central

    2015-01-01

    Within the last years 89Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting αvß3 integrins were synthesized using different conjugation strategies and labeled with 89Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [89Zr]FSC-RGD conjugates or [89Zr]triacetylfusarinine C (TAFC). Quantitative 89Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [89Zr]DFO, [89Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [89Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of 89Zr-based PET imaging agents. PMID:25941834

  16. Volcanic synchronization of Dome Fuji and Dome C Antarctic deep ice cores over the past 216 kyr

    NASA Astrophysics Data System (ADS)

    Fujita, S.; Parrenin, F.; Severi, M.; Motoyama, H.; Wolff, E. W.

    2015-10-01

    Two deep ice cores, Dome Fuji (DF) and EPICA Dome C (EDC), drilled at remote dome summits in Antarctica, were volcanically synchronized to improve our understanding of their chronologies. Within the past 216 kyr, 1401 volcanic tie points have been identified. DFO2006 is the chronology for the DF core that strictly follows O2 / N2 age constraints with interpolation using an ice flow model. AICC2012 is the chronology for five cores, including the EDC core, and is characterized by glaciological approaches combining ice flow modelling with various age markers. A precise comparison between the two chronologies was performed. The age differences between them are within 2 kyr, except at Marine Isotope Stage (MIS) 5. DFO2006 gives ages older than AICC2012, with peak values of 4.5 and 3.1 kyr at MIS 5d and MIS 5b, respectively. Accordingly, the ratios of duration (AICC2012 / DFO2006) range between 1.4 at MIS 5e and 0.7 at MIS 5a. When making a comparison with accurately dated speleothem records, the age of DFO2006 agrees well at MIS 5d, while the age of AICC2012 agrees well at MIS 5b, supporting their accuracy at these stages. In addition, we found that glaciological approaches tend to give chronologies with younger ages and with longer durations than age markers suggest at MIS 5d-6. Therefore, we hypothesize that the causes of the DFO2006-AICC2012 age differences at MIS 5 are (i) overestimation in surface mass balance at around MIS 5d-6 in the glaciological approach and (ii) an error in one of the O2 / N2 age constraints by ~ 3 kyr at MIS 5b. Overall, we improved our knowledge of the timing and duration of climatic stages at MIS 5. This new understanding will be incorporated into the production of the next common age scale. Additionally, we found that the deuterium signals of ice, δDice, at DF tends to lead the one at EDC, with the DF lead being more pronounced during cold periods. The lead of DF is by +710 years (maximum) at MIS 5d, -230 years (minimum) at MIS 7a and +60

  17. MICROBIAL IMPACTS ON THE MIGRATION OF ACTINIDES -EFFECTS OF EXUDATES ON ADSORPTION-

    SciTech Connect

    OHNUKI,T.; OZAKI, T.; YOSHIDA, T.; NANKAWA, T.; KOZAI, N.; SAKAMOTO, F.; SUZUKI, Y.; FRANCIS, A.J.

    2006-10-18

    The interaction of actinides with microorganisms has been extensively studied to elucidate migration behavior of actinides in the environments. However, the mechanisms of interaction of microorganisms and actinides are poorly understood. They have been conducting basic science on microbial accumulation of actinides in order to elucidate the environmental behavior of actinides under relevant conditions. The effect of exudates from bacteria cells on the sorption of Eu(III) and Cm(III) by Chlorella vulgaris was studied by a batch method. The pH dependence of log K{sub d} of Eu(III) and Cm(III) for cellulose, major component of C. vulgaris cell, differed from that for C. vulgaris. On the contrary, log K{sub d} of Eu(III) and Cm(III) for cellulose in the solution containing exudates from C. vulgaris cells in a 0.5% NaCl solution showed a similar pH dependence to that by C. vulgaris. These results strongly suggested that exudates affect on the sorption of Eu(III) and Cm(III) on C. vulgaris. Effect of desferrioxamine B (DFO), one of exudates to chelate the insoluble Fe(III), on the sorption of Pu(IV), Th(IV) and Eu(III) by Pseudomonas fluorescens was studied. In the presence of DFO the sorption of Pu(IV), Th(IV) and Eu(III) on the cells increased with a decrease in pH from 7 to 4. In contrast, without DFO most of Pu(IV), Th(IV) and Eu(III) were precipitated from solution. Adsorption of DFO on the cells was negligible in the solution with and without metals. Adsorption of Pu(IV), Th(IV) and Eu(III) on P. fluorescens cells decreased in the order Eu(III) > Th(IV) > Pu(IV), which corresponds to increasing stability constant of the DFO complexes. These results indicate that Th(IV), Pu(IV) and Eu(III) dissociate when in contact with cells, after which the metals are adsorbed.

  18. Evaluation of fingermark detection sequences on paper substrates.

    PubMed

    Marriott, Callie; Lee, Rebecca; Wilkes, Zachary; Comber, Bruce; Spindler, Xanthe; Roux, Claude; Lennard, Chris

    2014-03-01

    It is generally accepted that the amino acid reagent consisting of 1,2-indanedione and a catalytic amount of zinc chloride, referred to as IND-Zn, is the single best method for the detection of latent fingermarks on paper substrates and that ninhydrin is of limited value when used in sequence after this reagent. However, recent research has suggested that the sequence 1,8-diazafluoren-9-one (DFO) followed by ninhydrin may actually produce a greater number of fingermarks than IND-Zn on its own or IND-Zn followed by ninhydrin. This study focussed on the evaluation of two fingermark detection sequences for porous surfaces: (1) IND-Zn followed by ninhydrin, physical developer (PD) and the lipid stain nile red; and (2) DFO followed by ninhydrin, PD and nile red. The evaluation was undertaken using a range of latent fingermark donors and on a number of paper substrates that are commonly encountered in Australia. In addition, a pseudo-operational trial was completed on 5-year-old university examination booklets. Parallel studies were undertaken at two locations: Sydney (temperate, coastal climate) and Canberra (relatively dry, continental climate). The results of the donor study indicated that there was a negligible difference in performance between the two sequences across all paper types and all time periods evaluated. When considering individual reagents, IND-Zn generally developed better quality fingermarks compared to DFO; however, ninhydrin had a greater enhancement effect on DFO developed marks than after IND-Zn. In the pseudo-operational trials, the IND-Zn sequence outperformed the DFO sequence. Nile red did not develop any additional marks at the end of each sequence and, as a result, the use of this technique at the end of a full sequence is of questionable value. The overall outcome was that the sequence IND-Zn followed by ninhydrin and PD is recommended for the processing of common paper substrates under the conditions typically experienced at the two

  19. Organization of motor pools supplying the cervical musculature in a cryptodyran turtle, Pseudemys scripta elegans. I. Dorsal and ventral motor nuclei of the cervical spinal cord and muscles supplied by a single motor nucleus.

    PubMed

    Yeow, M B; Peterson, E H

    1986-01-08

    In this and the accompanying paper (Yeow and Peterson, '86) we characterize motor nuclei of the cervical spinal cord in Pseudemys scripta and the motor pools of eight cervical muscles. We have identified three motor nuclei that supply the cervical musculature by using serial reconstructions of Nissl-stained spinal cords cut in three cardinal planes, and in experimental cases in which horseradish peroxidase (HRP) was applied to individual neck muscles. These nuclei are named according to their position as visualized in the transverse plane: dorsal, ventral, and medial. A fourth (ventrolateral) motor nucleus was never labelled following application of HRP to the cervical musculature and presumably innervates the forelimbs. The dorsal motor nucleus occupies the mid-dorsal to dorsolateral ventral horn of C1 and C2. It is composed of at least two morphological groups of motor neurons; one of these is a population of very large, fusiform profiles with transversely oriented dendrites that is found primarily in C1. The ventral motor nucleus occupies the tip of the ventral horn from C1 to C8. Its cells are significantly smaller and more numerous in rostral than in caudal cervical segments. In Nissl material, ventral nuclear profiles show little tendency to cluster into subgroups, but experimental cases suggest that there is some spatial dissociation of different motor pools within the ventral nucleus. The medial motor nucleus is described in the accompanying paper together with the motor pools of three cervical muscles that it supplies. Having identified the cervical motor nuclei we then used retrograde transport of HRP to characterize the motor pools of individual cervical muscles. Two superficial ventral muscles (mm. coracohyoideus and plastro-squamosus) are supplied by dorsal nuclear cells. M. coracohyoideus motor neurons are significantly larger than those of m. plastrosquamosus and the very large, fusiform cell type is relatively more numerous in the m. coracohyoideus

  20. Novel trihydroxamate-containing peptides: design, synthesis, and metal coordination.

    PubMed

    Ye, Yunpeng; Liu, Min; Kao, Jeff L-F; Marshall, Garland R

    2006-01-01

    Novel trihydroxamate-containing peptides were designed to mimic desferrioxamine (Desferal(R), DFO, a naturally occurring siderophore) but possess distinct conformational restrictions and varied lipophilicity to probe structure vs. metal coordination. The synthesis was performed via fragment condensation of hydroxamate-containing oligopeptides such as Fmoc-Leu- Psi[CON(OBz)]-Phe-Ala-Pro-OH and H-Leu-Psi[CON(OBz)]-Phe-Ala-Pro-OBu(t) (Fmoc: 9-fluor enylmethoxycarbonyl; OBz: benzyl; OBu(t): tert-butyl) either in solution or on a solid support. The metal-binding properties were studied by electrospray ionization-mass spectroscopy (ESI-MS), ultraviolet (UV)-visible spectroscopy, and (1)H nuclear magnetic resonance (NMR). Similar to the dihydroxamate analogs previously explored [Biopolymers (Peptide Science), 2003, Vol. 71, pp. 489-515], the compounds with three hydroxamates arrayed at 10-atom intervals, i.e., H-[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3)-OH (P1), cyclo[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3) (P2), and H-[Leu-Psi(CONOH)-Phe-Ala-Pro](2)-Leu-NHOH (P7), exhibited high affinities for intramolecular coordination with Fe(III) and Ga(III). As expected, both P1 and P2 showed higher relative Fe(III)-binding affinities than the corresponding dihydroxamate-containing peptide analogs (P11 and P12). Even though both P1 and P2 did not compete with DFO in the relative metal-binding affinity in both solution and gas phases, P1, P2, and DFO exhibited similar relative binding selectivities to 11 different metal ions including Fe(III), Fe(II), Al(III), Ga(III), In(III), Zn(II), Cu(II), Co(II), Ni(II), Gd(III), and Mn(II). Compared to the other metal ions, they had higher relative binding affinities with Fe(III), Fe(II), Al(III), Ga(III), and In(III). The decreased metal-binding affinities of P1 and P2 in comparison with DFO suggested the conformational restrictions of their backbones perturb their three hydroxamate groups from optimal hexadentate orientations for metal coordination. As

  1. Self Assembly of Biogenic Surfactants at Mineral Surfaces and Their Effect on Biological Iron Acquisition

    NASA Astrophysics Data System (ADS)

    Kraemer, S. M.

    2005-12-01

    ) and 4 mg/l (RhL). Surfactant self assembly at the mineral surface influences the adsorption of organic ligands. We studied the adsorption of two siderophores, Desferrioxamine B (DFO-B) and Desferrioxamine D (DFO-D). These siderophores have identical ligating groups and backbone, but DFO-B is positively charged while DFO-D has no charge at pH 6 due to structural modifications of a terminal amine group. Finally, we studied the adsorption of EDTA, which is negatively charged at the experimental pH. We found increasing adsorption of DFO-B and DFO-D with increasing surfactant concentrations, indicating that hydrophobic interactions between the ligand and the adsorbed surfactant are more important than electrostatic attraction. This interpretation is consistent with the observation that the surfactant had no effect on EDTA adsorption which is twice negatively charged and hydrophilic. Siderophore controlled iron oxide dissolution rates increased with increasing surfactant concentrations up to 10 μM but slightly decreased at higher surfactant concentrations, despite a further increase of adsorbed siderophore concentrations. This indicates that the presence of low surfactant concentrations facilitates inner sphere surface complexation of siderophores. However, at high surfactant concentrations siderophores adsorb as outer sphere complexes, presumably by adsorption to the surfactant admicelle. Our results demonstrate that surfactants have an important effect on bio-mineral interactions.

  2. Coordination chemistry of two heavy metals: I, Ligand preferences in lead(II) complexation, toward the development of therapeutic agents for lead poisoning: II, Plutonium solubility and speciation relevant to the environment

    SciTech Connect

    Neu, Mary Patricia

    1993-11-01

    The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pKas and ligand-lead(II) stability constants of one hydroxamic acid and four thiohydroaxamic acids were determined. Solution thermodynamic results indicate that thiohydroxamic acids are more acidic and slightly better lead chelators than hydroxamates, e.g., N-methylthioaceto-hydroxamic acid, pKa = 5.94, logβ120 = 10.92; acetohydroxamic acid, pKa = 9.34, logβ120 = 9.52. The syntheses of lead complexes of two bulky hydroxamate ligands are presented. The X-ray crystal structures show the lead hydroxamates are di-bridged dimers with irregular five-coordinate geometry about the metal atom and a stereochemically active lone pair of electrons. Molecular orbital calculations of a lead hydroxamate and a highly symmetric pseudo octahedral lead complex were performed. The thermodynamic stability of plutonium(IV) complexes of the siderophore, desferrioxamine B (DFO), and two octadentate derivatives of DFO were investigated using competition spectrophotometric titrations. The stability constant measured for the plutonium(IV) complex of DFO-methylterephthalamide is logβ120 = 41.7. The solubility limited speciation of 242Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods.

  3. Protective effects of resveratrol against oxidative/nitrative modifications of plasma proteins and lipids exposed to peroxynitrite.

    PubMed

    Olas, Beata; Nowak, Pawel; Kolodziejczyk, Joanna; Ponczek, Michal; Wachowicz, Barbara

    2006-02-01

    The protective effects of resveratrol (3, 4', 5-trihydroxystilbene; present naturally in different plants) against the oxidative/nitrative damage of human plasma proteins induced by peroxynitrite (ONOO-) were studied and compared with those of deferoxamine (DFO; a natural siderophore isolated from Streptomyces pilosus), which is a typical and well-known antioxidant. We also studied the effect of ONOO- on plasma lipid peroxidation and the role of tested antioxidants in this process. ONOO- at the used concentrations (0.01-1 mM) showed toxicity to human plasma components. Exposure of plasma to ONOO- (0.1 mM) resulted in an increase of the level of carbonyl groups and nitrotyrosine residues in plasma proteins (approximately 4-fold and 76-fold, respectively) and in a distinct augmentation of lipid peroxidation (approximately 2-fold). In the presence of 0.1-mM resveratrol, a distinct decrease of carbonyl group formation and tyrosine nitration in plasma proteins caused by 0.1-mM ONOO- was observed (by approximately 70% and 65%, respectively). Addition of 0.1-mM DFO to plasma also distinctly reduced the level of carbonyl groups and nitrotyrosines caused by 0.1-mM ONOO- (by approximately 50% and 60%, respectively). Moreover, these antioxidants also inhibited plasma lipid peroxidation induced by ONOO- (0.1 mM). The obtained results indicate that in vitro resveratrol, like well-known antioxidant DFO, has inhibitory effects on ONOO- -mediated oxidation of proteins and lipids in human plasma.

  4. Relationship among Chelator Adherence, Change in Chelators, and Quality of Life in Thalassemia

    PubMed Central

    Trachtenberg, Felicia L.; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A.; Neufeld, Ellis J.; Yamashita, Robert

    2015-01-01

    Purpose Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of Health-Related Quality of Life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Methods Thalassemia Longitudinal Cohort participants in the US, UK, and Canada completed the SF-36v2 (ages 14+), and the PF-28 CHQ (parents of children<14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Results 258 adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8 years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly, due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from DFO infusion to oral deferasirox (p=0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical QOL. Conclusions Strategies to balance medical needs with family, work, and personal life may assist in adherence. PMID:24682717

  5. Medical Response, Search and Recovery during the Space Shuttle Columbia Accident Investigation

    NASA Technical Reports Server (NTRS)

    Stepaniak, Philip C.

    2010-01-01

    On February 1, 2003, the Space Shuttle Columbia broke apart during atmospheric re-entry on mission STS-107. After an event such as this, with high visibility and international interest, the operational challenge of recovering the crewmembers could not be underestimated. The Space Shuttle Program is organized to respond to a vehicle mishap using the resources of the Mishap Investigation Team (MIT). On the afternoon of Feb. 1, 2003, the MIT deployed to Barksdale Air Force Base (AFB), Louisiana. This location became the investigative center and interim storage location for crewmembers received from the Lufkin, Texas Disaster Field Office (DFO). The Lufkin DFO served as the primary area for all operations, including staging assets and deploying field teams for search, recovery and security of crewmember remains. More than 2,000 people from numerous organizations were involved with the recovery of the crew. All seven crewmembers of STS-107 were recovered and ceremonial last rights were administered. Astronaut and military personnel escorted the crew with honor to the MIT at Barksdale AFB, Louisiana. At Barksdale AFB a temporary morgue was established in an aircraft hangar and operated for approximately two weeks during which time coordination with the DFO field recovery teams, Armed Forces Institute of Pathology (AFIP) medical personnel, and the crew surgeons was on going. Families of crewmembers and NASA management were notified daily of the current findings. Working under the leadership of the MIT Lead, the medical team developed and executed a short-term plan to identify and relocate the crew with a military honor guard and protocol to the medical examiner at the Armed Forces Port Mortuary, Dover AFB, Delaware. After operations at Barksdale AFB were concluded the medical team transitioned back to Houston and a long-term plan was developed and implemented which involved the Air Force Mortuary Affairs at Randolph AFB, Texas. This plan was coordinated with search teams

  6. On the value of satellite-based river discharge and river flood data

    NASA Astrophysics Data System (ADS)

    Kettner, A. J.; Brakenridge, R.; van Praag, E.; Borrero, S.; Slayback, D. A.; Young, C.; Cohen, S.; Prades, L.; de Groeve, T.

    2015-12-01

    Flooding is the most common natural hazard worldwide. According to the World Resources Institute, floods impact 21 million people every year and affect the global GDP by $96 billion. Providing accurate flood maps in near-real time (NRT) is critical to their utility to first responders. Also, in times of flooding, river gauging stations on location, if any, are of less use to monitor stage height as an approximation for water surface area, as often the stations themselves get washed out or peak water levels reach much beyond their design measuring capacity. In a joint effort with NASA Goddard Space Flight Center, the European Commission Joint Research Centre and the University of Alabama, the Dartmouth Flood Observatory (DFO) measures NRT: 1) river discharges, and 2) water inundation extents, both with a global coverage on a daily basis. Satellite-based passive microwave sensors and hydrological modeling are utilized to establish 'remote-sensing based discharge stations'. Once calibrated, daily discharge time series span from 1998 to the present. Also, the two MODIS instruments aboard the NASA Terra and Aqua satellites provide daily floodplain inundation extent with global coverage at a spatial resolution of 250m. DFO's mission is to provide easy access to NRT river and flood data products. Apart from the DFO web portal, several water extent products can be ingested by utilizing a Web Map Service (WMS), such as is established with for Latin America and the Caribbean (LAC) region through the GeoSUR program portal. This effort includes implementing over 100 satellite discharge stations showing in NRT if a river is flooding, normal, or in low flow. New collaborative efforts have resulted in flood hazard maps which display flood extent as well as exceedance probabilities. The record length of our sensors allows mapping the 1.5 year, 5 year and 25 year flood extent. These can provide key information to water management and disaster response entities.

  7. Use of Iron Chelating Agents in Transfusion Dependent Thalassaemia Major Patients.

    PubMed

    Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P

    2015-10-01

    This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.

  8. A Kantian critique of cognitive psychotherapy.

    PubMed

    Yesavage, J A

    1980-01-01

    Modern cognitive psychotherapies such as those practiced by George Kelly, Aaron Beck, and Albert Ellis are examined from the perspective of Immanuel Kant's critique of eighteenth-century cognitive philosophy. Parallel strengths and weaknesses are found in the psychotherapeutic and philosophical systems. The major strengths of the systems are based upon their abilities to predict phenomena based upon an understanding of concepts used to organize experience. The major weaknesses of the systems arise when one takes such concepts to be too concrete. It is argued that modern psychiatrists interested in cognitive techniques may relearn some important but forgotten, facts about the strengths and limits of cognition by reviewing Kantian philosophy.

  9. A comparison of 15 theories of suicide.

    PubMed

    Lester, D

    1994-01-01

    A method is illustrated for studying the lives of suicidal individuals. Each of 15 theories of suicide is operationalized with 10 statements. These 150 statements are then rated as present or absent in the lives of 30 famous suicides for whom a biography is available. The theory of Aaron Beck is found to be most applicable to the suicidal lives and that of Sigmund Freud least applicable. A factor analysis has identified five clusters of theories; and the age, sex, national origin, era, and experience of loss are found to be associated with scores of the 30 suicides on the 15 theories.

  10. Future directions in anxiety disorders: profiles and perspectives of leading contributors.

    PubMed

    Norton, P J; Asmundson, G J; Cox, B J; Norton, G R

    2000-01-01

    Eight of the most influential clinicians and researchers in the study and treatment of anxiety disorders were identified by polling professional members of the Anxiety Disorders Association of America. These eight individuals are (in alphabetical order): James C. Ballenger, David H. Barlow, Aaron T. Beck, David M. Clark, Edna B. Foa, Rick G. Heimberg, Donald F. Klein, and Isaac M. Marks. Each offered their thoughts on a set of questions concerning the current and future status of the anxiety disorders field. Profiles and perspectives of these individuals are presented.

  11. Development of Data-Assimilation-Quality MODIS and MISR Over Ocean Aerosol Products

    DTIC Science & Technology

    2009-08-01

    graduate students in the Atmospheric Sciences Department, especially Prof. David Delene, Aaron Kennedy, Hongchun Jin, and Zhe Feng, for their technical...properties, as well as impact air quality (e.g. Wang and Christopher, 2003) and visibility (e.g. Appel et al., 1985). Studies have found that aerosols...16,988, July 27. 1997. Tong, Y. P., G. L. Zhang, M. G. Tan, W. Wang , J. M. Chen, Y. Hwu, P. C. Fsu, J. H. Je., G. Margaritondo, W. M. Song, R. F

  12. Platinum Acetylide Two-Photon Chromophores (Preprint)

    DTIC Science & Technology

    2007-04-01

    Reinhardt, B. A., Chern.Mater. 1990,2,660. 15. Larson, E . J.; Friesen , L. A.; Johnson, C. K., Chern.Phys. Lett. 1997,265, 161. 16. Albota, M.; Beljonee...PROJECT NUMBER 4348 5e. TASK NUMBER RG 6. AUTHOR(S) Joy E . Rogers (UES) Jonathan E . Slagle (AT&T Government Solutions) Douglas M. Krein (General...Chromophores 1,2Joy E . Rogers, 1,3Jonathan E . Slagle, 1,4Douglas M Krein, lAaron R. Burke, 1,5Benjamin C. Hal!, /.6Albert Fratini, 1,7Daniel G. McLean and

  13. Platinum Acetylide Two-Photon Chromophores (Postprint)

    DTIC Science & Technology

    2007-01-01

    L.; Pierce, B. M. Science 1994, 265, 632. (14) Prasad, P. N.; Reinhardt, B. A. Chem. Mater. 1990, 2, 660. (15) Larson, E . J.; Friesen , L. A.; Johnson...PROGRAM ELEMENT NUMBER 62102F 5d. PROJECT NUMBER 4348 5e. TASK NUMBER RG 6. AUTHOR(S) Joy E . Rogers (UES) Jonathan E . Slagle (AT&T Government...afford T1. Platinum Acetylide Two-Photon Chromophores Joy E . Rogers,†,‡ Jonathan E . Slagle,†,§ Douglas M. Krein,†,| Aaron R. Burke,†,| Benjamin C. Hall

  14. Summer Undergraduate Fellowships in Breast Cancer Research

    DTIC Science & Technology

    2007-05-01

    NE) F No E.P. Hasty 2003 Wickley, Aaron BYU-Hawaii (HI) M Yes H. Rao 2003 Wilson, Brian UT-Austin (TX) M No A. Tomkinson 2003 Yanez , Maria UT-Pan Am...AbileneChristianU. (TX) M No S.E. Lee 2004 Kim, Pamela Vassar College (NY) F No M. Gaczynska 2004 Martinez , Sonia Texas Lutheran U (TX) F Yes B. Chatterjee...Pamela Student participant Summer 2004 Martinez , Sonia Student particpant Summer 2004 McDonald, Samuel Student participant Summer 2006 Moshfeghian

  15. Eastern Renewable Generation Integration Study: Flexibility and High Penetrations of Wind and Solar; NREL (National Renewable Energy Laboratory)

    SciTech Connect

    Bloom, Aaron; Townsend, Aaron; Palchak, David

    2015-07-29

    Balancing wind and solar in a model is relatively easy. All you need to do is assume a very large system with infinite flexibility! But what if you don't have an infinitely flexible system? What if there are thousands of generators nestled in a handful of regions that are unlikely to change their operational practices? Would you still have enough flexibility to balance hundreds of gigawatts of wind and solar at a 5 minute level? At NREL, we think we can, and our industry partners agree. This presentation was presented at the IEEE Power and Energy Society General Meeting by Aaron Bloom, highlighting results of the Eastern Renewable Generation Integration Study.

  16. Hazing in the U.S. Armed Forces: Recommendations for Hazing Prevention Policy and Practice

    DTIC Science & Technology

    2015-01-01

    negative behaviors within the institution or organization (Vreeman and Carroll , 2007). Applying these general ideas about levels of change to the context...Scientist, Vol. 92, No. 2, March–April 2004, pp. 166–172. 122 Hazing in the U.S. Armed Forces Sosis, Richard, and Bradley J. Rue, “Religious Ritual and...Vreeman, Rachel C., and Aaron E. Carroll , “A Systematic Review of School- Based Interventions to Prevent Bullying,” Archives of Pediatric Adolescent

  17. Technical Basis for Flood Protection at Nuclear Power Plants

    DTIC Science & Technology

    2015-07-01

    ER D C/ CH L SR -1 5- 3 Technical Basis for Flood Protection at Nuclear Power Plants Co as ta l a nd H yd ra ul ic s La bo ra to ry...2015 Technical Basis for Flood Protection at Nuclear Power Plants James R. Leech, Loren L. Wehmeyer, David A. Margo, Landris T. Lee, Aaron R. Byrd...39180-6199 ERDC/CHL SR-15-3 ii Abstract Current flood- protection regulatory guidance for nuclear power plants is contained in the Regulatory Guide

  18. Morphological Characteristics of L-Band Scintillations and Their Impact on GPS Signals - A Quantitative Study on the Precursors for the Occurrence of Scintillations

    DTIC Science & Technology

    2006-06-01

    8.47oN, 76.91oE, 0.9oN dip) and the another at an off equatorial station Waltair (17.7oN, 83.3oE, 20oN dip) and the ionograms are recorded at 15...105 el/cm3. The virtual height of the 4 MHz return signal (h’F) on the ionograms of the equatorial station Trivandrum is scaled at 15 minute...appearing on equatorial ionograms , J. Geophys. Res., 66, 3125,1961 [9] DasGupta, A., Aarons, Basu, S., J., Klobuchar, J. A., Basu, Su., and Bushby, A

  19. Toward the Effective and Efficient Measurement of Implementation Fidelity

    PubMed Central

    Schoenwald, Sonja K.; Garland, Ann F.; Chapman, Jason E.; Frazier, Stacy L.; Sheidow, Ashli J.; Southam-Gerow, Michael A.

    2011-01-01

    Implementation science in mental health is informed by other academic disciplines and industries. Conceptual and methodological territory charted in psychotherapy research is pertinent to two elements of the conceptual model of implementation posited by Aarons and colleagues (2010)—implementation fidelity and innovation feedback systems. Key characteristics of scientifically validated fidelity instruments, and of the feasibility of their use in routine care, are presented. The challenges of ensuring fidelity measurement methods are both effective (scientifically validated) and efficient (feasible and useful in routine care) are identified as are examples of implementation research attempting to balance these attributes of fidelity measurement. PMID:20957425

  20. Preparing for the Future: The Regional Alignment of U.S. Army Brigade Combat Teams

    DTIC Science & Technology

    2013-06-14

    threats for the U.S. in the next two decades (Krepinevich, Martinage, and Work 2008, 2). Aaron Friedberg , a Professor of Politics and International Affairs...in the Office of the Vice President, echoes the same message. In his Foreign Affairs article, “Bucking Beijing,” Friedberg warns that “absent a strong...the region” ( Friedberg 2012, 51). The threat of A2/AD technology and China are inseparable. China is a threat because it possesses A2/AD technology

  1. Passing through the wall: on outings, exodus, angels, and the ark.

    PubMed

    Wassersug, Richard Joel

    2009-09-01

    Classicists have argued that angels in Christian theology were modeled on the eunuchs of antiquity; with angels providing the same services to the Lord in Heaven that eunuchs provided to emperors on Earth. I apply this idea toward understanding the cherubim on the ark in Exodus 25 and the death of Aaron's sons in Leviticus 10. I also suggest that the angel-eunuch analogy can help us understand the psychological impact of androgen deprivation therapy on modern prostate cancer patients. Appreciating this analogy can help prostate cancer patients accept and adapt to the changes they experience.

  2. Entropic Elastic Processes in Protein Mechanisms. Part 2. Simple (Passive) and Coupled (Active) Development of Elastic Forces,

    DTIC Science & Technology

    1986-01-01

    1981). Biopolymers 20, 124/-1ZbU. Aaron, B. B. and Gosline, J. M . (1980). Nature 281, 8 6-86/. Aksoy, M . 0., Williams. D., Sharkey, E . M . and...Barone, L. M ., Faris, B., Chipman, S. D., Toselli , P., Oakes, B. W. and Franz- blau, C. (1985). Biochim. Biophys. Acta. 840, 245-254. Berg, R. A. and...Physica 7, 284-304. Kubler, D., Pyerin, W., Burow, E . and Kinzel, V. (1983). Proc. Natl. Acad. Sci. USA 80, 4021-4025. Kuhn, C., Yu, S.-Y., Chraplyvy, M

  3. JSC Mission Control Center (MCC) personnel watch STS-26 landing in FCR

    NASA Technical Reports Server (NTRS)

    1988-01-01

    During STS-26 Discovery, Orbiter Vehicle (OV) 103, landing, personnel in JSC's Mission Control Center (MCC) Bldg 30 flight control room (FCR) monitor heading alignment cone (HAC) diagram and OV-103 runway touch down displayed on front screens. In the foreground is the Specialists Console (BOOSTER, EVA, PDRS, RMS, PAM, IUS) with Mission Operations Directorate (MOD) console next to it. At the MOD console are Flight Crew Operations Directorate (FCOD) Deputy Chief Henry Hartsfield, JSC Director Aaron Cohen, and MOD Director Eugene F. Kranz. In the background, Public Affairs Office (PAO) photographer Andrew R. 'Pat' Patnesky takes a photograph of the FCR activity.

  4. MOCR activity during Day 4 of STS-3 mission

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Major General J.A. Abrahamson, right, talks to JSC Director Christopher C. Kraft, Jr., (seated left) and Space Shuttle Program Manager Glynn S. Lunney on the back row of consoles in the mission operations control room (MOCR) in the Johnson Space Center mission control center. The reflection behind the men is a window for the MOCR viewing room (28772,28775); Abrahamson, second right, talks to JSC's Aaron Cohen, right, as Kraft (seated left) and Lunney listen in mission control (28773); Flight controller J.E. Connor monitors a television transmission from the Space Shuttle Columbia during day 4 of the STS-3 mission. Conner is seated at his INCO console (28774).

  5. Deferoxamine Expedites Consolidation during Mandibular Distraction Osteogenesis

    PubMed Central

    Donneys, Alexis; Deshpande, Sagar S.; Tchanque-Fossuo, Catherine N.; Johnson, Kelsey L.; Blough, Jordan T.; Perosky, Joseph E.; Kozloff, Kenneth M.; Felice, Peter A.; Nelson, Noah S.; Farberg, Aaron S.; Levi, Benjamin; Buchman, Steven R.

    2014-01-01

    Background A limitation of mandibular Distraction Osteogenesis (DO) is the length of time required for consolidation. This drawback subjects patients to possible pin-site infections, as well as a prolonged return to activities of normal daily living. Developing innovative techniques to abridge consolidation periods could be immensely effective in preventing these problematic morbidities. Deferoxamine (DFO) is an angiogenic activator that triggers the HIF-1α pathway through localized iron depletion. We previously established the effectiveness of DFO in enhancing regenerate vascularity at a full consolidation period (28 days) in a murine mandibular DO model. To investigate whether this augmentation in vascularity would function to accelerate consolidation, we progressively shortened consolidation periods prior to μCT imaging and biomechanical testing (BMT). Materials and Methods Three time points (14d, 21d and 28d) were selected and six groups of Sprague-Dawley rats (n=60) were equally divided into control (C) and experimental (E) groups for each time period. Each group underwent external fixator placement, mandibular osteotomy, and a 5.1mm distraction. During distraction, the experimental groups were treated with DFO injections into the regenerate gap. After consolidation, mandibles were imaged and tension tested to failure. ANOVA was conducted between groups, and p < 0.05 was considered statistically significant. Results At 14 days of consolidation the experimental group demonstrated significant increases in Bone Volume Fraction (BVF), Bone Mineral Density (BMD) and Ultimate Load (UL) in comparison to non-treated controls. The benefit of treatment was further substantiated by a striking 100% increase in the number of bony unions at this early time-period (C:4/10 vs. E:8/10). Furthermore, metrics of BVF, BMD, Yield and UL at 14 days with treatment demonstrated comparable metrics to those of the fully consolidated 28d control group. Conclusion Based on these

  6. Modulation of Membrane Lipid Composition and Homeostasis in Salmon Hepatocytes Exposed to Hypoxia and Perfluorooctane Sulfonamide, Given Singly or in Combination

    PubMed Central

    Olufsen, Marianne; Cangialosi, Maria V.; Arukwe, Augustine

    2014-01-01

    The relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 µM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1α mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that biological responses related to peroxisome proliferation (peroxisome proliferator-activated receptors (PPARs) and acyl coenzyme A (ACOX)) and FA desaturation (Δ5- and Δ6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by PFOSA and chemically induced hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to

  7. Catalysis by orotidine 5'-monophosphate decarboxylase: effect of 5-fluoro and 4'-substituents on the decarboxylation of two-part substrates.

    PubMed

    Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L; Richard, John P

    2013-01-22

    The syntheses of two novel truncated analogs of the natural substrate orotidine 5'-monophosphate (OMP) for orotidine 5'-monophosphate decarboxylase (OMPDC) with enhanced reactivity toward decarboxylation are reported: 1-(β-d-erythrofuranosyl)-5-fluoroorotic acid (FEO) and 5'-deoxy-5-fluoroorotidine (5'-dFO). A comparison of the second-order rate constants for the OMPDC-catalyzed decarboxylations of FEO (10 M⁻¹ s⁻¹) and 1-(β-d-erythrofuranosyl)orotic acid (EO, 0.026 M⁻¹ s⁻¹) shows that the vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent of FEO. The OMPDC-catalyzed decarboxylations of FEO and EO are both activated by exogenous phosphite dianion (HPO₃²⁻), but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction of FEO. This provides strong evidence that the phosphite-activated OMPDC-catalyzed reaction of FEO is not limited by the chemical step of decarboxylation of the enzyme-bound substrate. Evidence is presented that there is a change in the rate-limiting step from the chemical step of decarboxylation for the phosphite-activated reaction of EO, to closure of the phosphate gripper loop and an enzyme conformational change at the ternary E•FEO•HPO₃²⁻ complex for the reaction of FEO. The 4'-CH₃ and 4'-CH₂OH groups of 5'-dFO and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4'-CH₃ group of 5'-dFO and the 4'-CH₂OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation. Here, the destabilizing effect of the 4'-CH₃ substituent at 5'-dFO is masked by the rate-limiting conformational change that depresses the third-order rate constant for the phosphite-activated reaction of the parent substrate FEO.

  8. High Energy Theory Workshops and Visitors at the Michigan Center for Theoretical Physics FY15

    SciTech Connect

    Pierce, Aaron T.

    2015-09-18

    The String theory workshop was held from March 4-7, 2015 on the University of Michigan campus. Local organizers were Gordon Kane and Aaron Pierce. Piyush Kumar (Yale), Jim Halverson (KITP), Bobby Acharya (ICTP) and Sven Krippendorf (Oxford) served as external organizers.The meeting focused on the status of work to project 10 or 11 dimensional string/M theories onto our 4 spacetime dimensions (compactification). The workshop had 31 participants, half from outside the U.S. Participants were encouraged to focus on predictions for recent and forthcoming data, particularly for Higgs physics and LHC and dark matter, rather than on the traditional approach of embedding the Standard Model particles and forces. The Higgs boson sympoosium was locally organized by James Wells (chair), Aaron Pierce and Jianming Qian. Additional input in the early stages by Stefan Pokorski (Warsaw) who was unable to attend in the end. The workshop consistent of 22 talks from experts around the world, both theoretical and experimental. Experimentalists summarized the current state of knowledge of the Higgs boson and its varients. The theory talks ranged from technical calculations of Standard Model processes to speculative novel ideas. The YHET visitor program invited weekly young visitors to the University of Michigan campus to present their work. This year 24 participants came under the program, with 17 of them receiving at least partial support for their visits.

  9. Effect of deferrioxamine and diethyldithiocarbamate on paracetamol-induced hepato- and nephrotoxicity. The role of lipid peroxidation.

    PubMed

    Younes, M; Sause, C; Siegers, C P; Lemoine, R

    1988-08-01

    In mice subjected to glutathione depletion by pretreatment with phorone (diisopropylidene acetone, 200 mg/kg i.p. in 10 ml/kg olive oil) paracetamol (acetaminophen, 300 mg/kg p.o. in 10 ml/kg tylose 2 h later) led to a marked hepatotoxicity as evidenced by increased plasma activities of the liver-specific enzymes sorbitol dehydrogenase (SDH) and glutamate-pyruvate-transaminase (GPT) 3 and 24 h after treatment. Nephrotoxicity was also indicated at both timepoints by an increased creatinine concentration in plasma, while neither the urine volume nor its content in gamma-glutamyl transpeptitase over 20 h were affected. Hepato- and nephrotoxicity were also assessed histomorphologically. In vivo lipid peroxidation (LPO), as measured by ethane exhalation over 3 h, was clearly enhanced by paracetamol. Malondialdehyde content was increased and glutathione concentration diminished in the liver, but not in the kidney. Diethyldithiocarbamate (DTC, 200 mg/kg i.p.) or deferrioxamine (DFO, 500 mg/kg i.p.) both given 30 min before PA, inhibited in vivo LPO. However, only DTC was capable of antagonizing the hepato- and nephrotoxic effects of paracetamol, while DFO only delayed the onset of nephrotoxicity but left the hepatotoxicity unaffected. Both agents inhibited the rise in hepatic malondialdehyde-content, but only DTC prevented paracetamol-induced glutathione depletion. These results indicate that LPO is not mainly responsible for paracetamol toxicity towards liver or kidney.

  10. An analysis of space scales for sea ice drift

    SciTech Connect

    Carrieres, T.

    1994-12-31

    Sea ice presents a hazard to navigation off Canada`s east coast from January to June. The Ice Centre Environment Canada (ICEC) which is part of the Atmospheric Environment Service monitors ice conditions in order to assist safe and efficient operations through or around the ice. The ice program depends on an advanced data acquisition, analysis and forecasting effort. Support for the latter is provided by kinematic models as well as a fairly simple dynamic sea ice model. In order to improve ICEC`s forecasting capabilities, the Department of Fisheries and Oceans (DFO) conducts ice modelling research and regular field experiments. The experiments provide a better understanding of the ice and also allow models to be validated and refined. The Bedford Institute of Oceanography (BIO, part of DFO) regularly deploys beacons on ice floes off the Labrador and Newfoundland coasts. These beacons provide environmental as well as location information through Service ARGOS. Documentation on the accuracy and information of the sensors is documented in Prinsenberg, 1993. The beacon locations are used here to infer an relatively unbiased representation of sea ice drift.

  11. Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain.

    PubMed

    Tonin, Anelise M; Grings, Mateus; Busanello, Estela N B; Moura, Alana P; Ferreira, Gustavo C; Viegas, Carolina M; Fernandes, Carolina G; Schuck, Patrícia F; Wajner, Moacir

    2010-07-01

    Accumulation of long-chain 3-hydroxy fatty acids is the biochemical hallmark of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies. These disorders are clinically characterized by neurological symptoms, such as convulsions and lethargy, as well as by cardiomyopathy and muscle weakness. In the present work we investigated the in vitro effect of 3-hydroxydodecanoic (3HDA), 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, which accumulate in these disorders, on important oxidative stress parameters in cerebral cortex of young rats in the hope to clarify the mechanisms leading to the brain damage found in patients affected by these disorders. It was first verified that these compounds significantly induced lipid peroxidation, as determined by increased thiobarbituric acid-reactive substances levels. In addition, carbonyl formation was significantly increased and sulfhydryl content decreased by 3HTA and 3HPA, which indicates that these fatty acids elicit protein oxidative damage. 3HTA and 3HPA also diminished the reduced glutathione (GSH) levels, without affecting nitrate and nitrite production. Finally, we observed that the addition of the antioxidants and free radical scavengers trolox and deferoxamine (DFO) was able to partially prevent lipid oxidative damage, whereas DFO fully prevented the reduction on GSH levels induced by 3HTA. Our present data showing that 3HDA, 3HTA and 3HPA elicit oxidative stress in rat brain indicate that oxidative damage may represent an important pathomechanism involved in the neurologic symptoms manifested by patients affected by LCHAD and MTP deficiencies.

  12. Adsorption of Pb(ll) and Eu(III) by oxide minerals in the presence of natural and synthetic hydroxamate siderophores.

    PubMed

    Kraemer, Stephan M; Xu, Jide; Raymond, Kenneth N; Sposito, Garrison

    2002-03-15

    Trihydroxamate siderophores have been proposed for use as mediators of actinide and heavy metal mobility in contaminated subsurface zones. These microbially produced ligands, common in terrestrial and marine environments, recently have been derivatized synthetically to enhance their affinity for transuranic metal cations. However, the interactions between these synthetic derivative and adsorbed trace metals have not been characterized. In this paper we compare a natural siderophore, desferrioxamine-B (DFO-B), with its actinide-specific catecholate derivative, N-(2,3-dihydroxy-4-(methylamido)benzoyl)desferrioxamine-B (DFOMTA), as to their effect on the adsorption of Pb(II) and Eu(III) by goethite and boehmite. In the presence of 240 microM DFO-B, a strongly depleting effect on Eu(III) adsorption by goethite and boehmite occurred above pH 6. By contrast, almost total removal of Eu(III) from solution in the neutral to slightly acidic pH range was observed in the presence of either 10 or 100 microM DFOMTA, due primarilyto the formation of metal-DFOMTA precipitates. Addition of DFOMTA caused an increase in Pb(II) adsorption by goethite below pH 5, but a decrease above pH 5, such that the Pb(II) adsorption edge in the presence of DFOMTA strongly resembled the DFOMTA adsorption envelope, which showed a maximum near pH 5 and decreasing adsorption toward lower and higher pH.

  13. Mishap Investigation Team (MIT) - Barksdale AFB, Louisiana

    NASA Technical Reports Server (NTRS)

    Stepaniak, Philip

    2005-01-01

    The Shuttle Program is organized to support a Shuttle mishap using the resources of the MIT. The afternoon of Feb. 1, 2003, the MIT deployed to Barksdale AFB. This location became the investigative center and interim storage location for crewmembers received from the Lufkin Disaster Field Office (DFO). Working under the leadership of the MIT Lead, the medical team executed a short-term plan that included search, recovery, and identification including coordination with the Armed Forces Institute of Pathology Temporary operations was set up at Barksdale Air Force Base for two weeks. During this time, coordination with the DFO field recovery teams, AFIP personnel, and the crew surgeons was on going. In addition, the crewmember families and NASA management were updated daily. The medical team also dealt with public reports and questions concerning biological and chemical hazards, which were coordinated with SPACEHAB, Inc., Kennedy Space Center (KSC) Medical Operations and the Johnson Space Center (JSC) Space Medicine office. After operations at Barksdale were concluded the medical team transitioned back to Houston and a long-term search, recovery and identification plan was developed.

  14. The role of iron in the proliferation of Drosophila l(2)mbn cells

    SciTech Connect

    Metzendorf, Christoph; Lind, Maria I.

    2010-09-24

    Research highlights: {yields} Establishment of a model system to study the role of iron during proliferation. {yields} Iron deprivation of insect tumorous cell line inhibits cell proliferation. {yields} Iron deprivation causes a reversible cell cycle arrest in G1/S-phase. {yields} Iron deprivation promotes decreased gene expression of cycE. -- Abstract: Iron is essential for life and is needed for cell proliferation and cell cycle progression. Iron deprivation results first in cell cycle arrest and then in apoptosis. The Drosophila tumorous larval hemocyte cell line l(2)mbn was used to study the sensitivity and cellular response to iron deprivation through the chelator desferrioxamine (DFO). At a concentration of 10 {mu}M DFO or more the proliferation was inhibited reversibly, while the amount of dead cells did not increase. FACS analysis showed that the cell cycle was arrested in G1/S-phase and the transcript level of cycE was decreased to less than 50% of control cells. These results show that iron chelation in this insect tumorous cell line causes a specific and coordinated cell cycle arrest.

  15. Determination of efficacy of fingermark enhancement reagents; the use of propyl chloroformate for the derivatization of fingerprint amino acids extracted from paper.

    PubMed

    Mink, Tineke; Voorhaar, Annelies; Stoel, Reinoud; de Puit, Marcel

    2013-09-01

    The analysis of the constituents of fingerprints has been described numerous times, mainly with the purpose of determining the aging effect on fingerprints or showing the differences between donors or groups of donors. In this paper we describe the use of derivatized amino acids to determine the efficacy of the visualization reagents 1,8-diazafluoren-9-one (DFO) and ninhydrin. At present certain conditions are used for the application of these reagents, as determined by trial-and-error investigations, to the effect on fingerprints. The recovery of amino acids from a porous surface can be used as a measure for the efficacy of a visualization agent. In this paper we describe a method for the determination of the amount of amino acid left after reaction with well known fingerprint visualization reagents. This will allow a more scientific approach to method development for fingermark enhancement techniques. Furthermore, investigations on the influence of the concentration of fingermark amino acids, the order of application of and exposure time to reagents and the influence of age of the amino acids were carried out. These studies have resulted in a broader understanding of the mechanism involved in visualization of fingermarks using DFO and ninhydrin.

  16. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    SciTech Connect

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-10-25

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics.

  17. Iron chelators in medicinal applications - chemical equilibrium considerations in pharmaceutical activity.

    PubMed

    Manning, Thomas; Kean, Greg; Thomas, Jessica; Thomas, Khaleh; Corbitt, Michael; Gosnell, Donna; Ware, Ronald; Fulp, Sonya; Jarrard, Joey; Phillips, Dennis

    2009-01-01

    Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] --> [Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

  18. Laboratory evaluation of a new delivery system to improve patient compliance with chelation therapy.

    PubMed

    Lombardo, T; Frontini, V; Ferro, G; Sergi, P; Guidice, A; Lombardo, G

    1996-03-01

    As thalassaemia patients live longer, compliance with chelation therapy becomes more and more of a problem. Teenagers rebel against the continual need for treatment, and young adults with jobs, active social lives and families, find it hard to find the time to prepare and deliver their treatments. In an effort to find a solution to this problem, we evaluated a non-electronic, disposable pump (Infusor 5 ml/h, Baxter Healthcare) to determine its suitability for high dose desferrioxamine (DFO) infusions. We wanted an infusion time of 12 h to support overnight delivery in the patient's home. Because of DFOs viscosity, infusion times vary at different concentrations. We found the optimal prescription for total delivery within 12 h to be a dose of 70 mg/kg x patient's body weight diluted in constant volume of 40 ml of water for injection. Our tests were carried out in vitro and the results show that the 5 ml/h Infusor may be used to deliver high dose DFO chelation therapy within 12 h. The variability of the flow rate, dependent on the concentration of the solution, and the absence of a warning system, are more than compensated for by the simplicity of the pump.

  19. FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of structural changes in the liver tissues of mice due to aluminum exposure

    NASA Astrophysics Data System (ADS)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

    2014-01-01

    The present study inform the alterations on major biochemical constituents such as lipids, proteins, nucleic acids and glycogen along with phosphodiester linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations, aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the area value significant decrease due structural alteration in the protein, glycogen and triglycerides levels but chelating agents DFP and DFO upturned it. Morphology changes by aluminium induced alterations and recovery by chelating agents within liver tissues known by histopathological examination. Concentrations of trace elements were found by ICP-OES. FT-Raman study was revealed to be in agreement with biochemical studies and demonstrate that it can successfully specify the molecular alteration in liver tissues. The tyrosyl doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but treatment with DFP and DFO + DFP brings back to nearer control value. This indicates more variation in the hydrogen bonding of the phenolic hydroxyl group due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400) observed in the aluminum induced tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the aluminum intoxicated liver tissues. Finally, FT-Raman spectroscopy might be a useful tool for obtained successfully to indicate the molecular level changes.

  20. Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

    PubMed Central

    Mosayebnia, Mona; Shafiee-Ardestani, Mehdi; Pasalar, Parvin; Mashayekhi, Mojgan; Amanlou, Massoud

    2014-01-01

    Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. Materials and Methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG) was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2) cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO), a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide MTT assay as well. Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems. Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage. PMID:24554907

  1. Oxidation-Induced Degradable Nanogels for Iron Chelation

    NASA Astrophysics Data System (ADS)

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-02-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

  2. Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin.

    PubMed

    Li, Yanyan; Chen, Man; Xu, Yanyan; Yu, Xiao; Xiong, Ting; Du, Min; Sun, Jian; Liu, Liegang; Tang, Yuhan; Yao, Ping

    2016-01-01

    Iron, in its free ferrous states, can catalyze Fenton reaction to produce OH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD). As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories) were cotreated by quercetin or deferoxamine (DFO) for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP) and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD.

  3. Dispersant Effectiveness, In-Situ Droplet Size Distribution and ...

    EPA Pesticide Factsheets

    This report summarizes two projects covered under an Interagency Agreement between the Bureau of Safety and Environmental Enforcement (BSEE) and the U.S. Environmental Protection Agency (EPA) in collaboration with the Bedford Institute of Oceanography, Department of Fisheries and Oceans Canada (BIO DFO), New Jersey Institute of Technology (NJIT) and Dalhousie University. Both projects dovetail together in addressing the ability to differentiate physical from chemical dispersion effectiveness using dispersed oil simulations within a flume tank for improving forensic response monitoring tools. This report is split into separateTasks based upon the two projects funded by BSEE: 1) Dispersant Effectiveness, In-Situ Droplet Size Distribution and Numerical Modeling to Assess Subsurface Dispersant Injection as a Deepwater Blowout Oil Spill Response Option. 2) Evaluation of Oil Fluorescence Characteristics to Improve Forensic Response Tools. This report summarizes 2 collaborative projects funded through an Interagency Agreement with DOI BSEE and a Cooperative Agreement with DFO Canada. BSEE required that the projects be combined into one report as they are both covered under the one Interagency Agreement. Task B (Fluorescence of oils) is an SHC 3.62 FY16 product.

  4. Oxidation-Induced Degradable Nanogels for Iron Chelation

    PubMed Central

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-01-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

  5. Lack of mitochondrial DNA impairs chemical hypoxia-induced autophagy in liver tumor cells through ROS-AMPK-ULK1 signaling dysregulation independently of HIF-1α.

    PubMed

    Marin, Jose J G; Lozano, Elisa; Perez, Maria J

    2016-12-01

    Alterations in mitochondrial DNA (mtDNA) and autophagy activation are common events in tumors. Here we have investigated the effect of mitochondrial genome depletion on chemical hypoxia-induced autophagy in liver tumor cells. Human SK-Hep-1 wild-type and mtDNA-depleted (Rho) cells were exposed to the hypoxia mimetic agents CoCl2 and deferoxamine (DFO). Up-regulation of HIF-1α, but not HIF-2α was observed. The expression of several HIF-1α target genes was also found. In human SK-Hep-1 and mouse Hepa 1-6 liver tumor cells, but not in the counterpart Rho derived lines, chemical hypoxia increased the abundance of autophagosomes and autolysosomes. In wild-type and Rho cells, chemical hypoxia induced down-regulation of HIF-1α-dependent autophagy inhibitors Bcl-2 and mTOR, whereas activation of AMPK/ULK1-mediated pro-autophagy pathway occurred only in wild-type cells. Chemical (compound C) and genetic (shRNA) inhibition of AMPK activation resulted in reduced autophagy. ATP levels were similar in both cell types, whereas constitutive and chemical hypoxia-induced reactive oxygen species (ROS) generation was lower in Rho cells. In wild-type cells, the antioxidant N-acetylcysteine blocked CoCl2- and DFO-induced AMPK and autophagy activation, but not endoplasmic reticulum stress induced by CoCl2. Enhanced Bax-α/Bcl-2 ratio and cell death was induced by hypoxia mimetic agents more markedly in wild-type than in Rho cells. Upon blocking autophagy activation with 3-methyladenine, DFO-induced cell death was partially prevented whereas that induced by CoCl2 was increased, but only in wild-type cells. These results suggest that mitochondrial dysfunction associated with the lack of mtDNA impairs the signaling pathways mediated by ROS, controlling autophagy activation in liver tumor cells, which may contributes to cancer development.

  6. Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.

    PubMed

    Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B; Kalinowski, Danuta S; Lovejoy, David B; Lane, Darius J R; Richardson, Des R

    2013-12-01

    Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.

  7. Transport of subsurface bacteria in porous media. Final report

    SciTech Connect

    Arnold, R.G.; Baygents, J.C.; Ogden, K.L.

    1998-05-01

    The aims of our project have not changed significantly since the original proposal. Our primary goals were to support field experiments by screening strains of bacteria to find favorable transport characteristics among field isolates and to estimate collision efficiencies for those bacteria in typical Oyster site sediments. The data we obtained were disseminated to other members of the subprogram. For example, Tim Ginn of PNL incorporated our results into his field model; Aaron Mills used our work for comparison purposes; and John Wilson used our results to determine if there is a correlation between facies type and cell adhesion. Copies of all information were also sent to Mary DeFlaun of Envirogen for incorporation into the Sample Tables. In addition to the originally proposed work, we performed longer column studies, examining the effects of aluminum, iron, and water chemistry on bacterial transport, and beginning to understand the role of electrostatic interactions as determinants of biocolloid/collector affinity.

  8. A new pathogenic Leptospira, not readily cultivated.

    PubMed

    ALEXANDER, A D; STOENNER, H G; WOOD, G E; BYRNE, R J

    1962-04-01

    Alexander, Aaron D. (Walter Reed Army Institute of Research, Washington, D.C.), Herbert G. Stoenner, Garnett E. Wood, and Robert J. Byrne. A new pathogenic Leptospira, not readily cultivated. J. Bacteriol. 83:754-760. 1962.-A pathogenic Leptospira was isolated from water of the Grand River, (S.D.) that differed significantly from other known leptospirae in that it could not be cultivated in conventional leptospiral media. Growth was promoted in Fletcher's medium modified to contain 20% rabbit serum. The isolate, after several serial passages, was lethal for hamsters. It could not be adapted to grow in the chick embryo. Guinea pigs and calves inoculated with the isolate developed febrile and antibody responses but showed no other overt signs of disease. The strain was identified on the basis of cross-agglutination and agglutinin-adsorption tests as a new subserotype of Leptospira naam and was therefore designated as L. naam, subserotype dakotii.

  9. G-quadruplexes and their regulatory roles in biology

    PubMed Central

    Rhodes, Daniela; Lipps, Hans J.

    2015-01-01

    ‘If G-quadruplexes form so readily in vitro, Nature will have found a way of using them in vivo’ (Statement by Aaron Klug over 30 years ago). During the last decade, four-stranded helical structures called G-quadruplex (or G4) have emerged from being a structural curiosity observed in vitro, to being recognized as a possible nucleic acid based mechanism for regulating multiple biological processes in vivo. The sequencing of many genomes has revealed that they are rich in sequence motifs that have the potential to form G-quadruplexes and that their location is non-random, correlating with functionally important genomic regions. In this short review, we summarize recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance. We also highlight remaining open questions that will have to be addressed in the future. PMID:26350216

  10. Social Network Analysis for Program Implementation

    PubMed Central

    Valente, Thomas W.; Palinkas, Lawrence A.; Czaja, Sara; Chu, Kar-Hai; Brown, C. Hendricks

    2015-01-01

    This paper introduces the use of social network analysis theory and tools for implementation research. The social network perspective is useful for understanding, monitoring, influencing, or evaluating the implementation process when programs, policies, practices, or principles are designed and scaled up or adapted to different settings. We briefly describe common barriers to implementation success and relate them to the social networks of implementation stakeholders. We introduce a few simple measures commonly used in social network analysis and discuss how these measures can be used in program implementation. Using the four stage model of program implementation (exploration, adoption, implementation, and sustainment) proposed by Aarons and colleagues [1] and our experience in developing multi-sector partnerships involving community leaders, organizations, practitioners, and researchers, we show how network measures can be used at each stage to monitor, intervene, and improve the implementation process. Examples are provided to illustrate these concepts. We conclude with expected benefits and challenges associated with this approach. PMID:26110842

  11. The Need for Specific Penalties for Hacking in Criminal Law

    PubMed Central

    Oh, Sangkyo; Lee, Kyungho

    2014-01-01

    In spite of the fact that hacking is a widely used term, it is still not legally established. Moreover, the definition of the concept of hacking has been deployed in a wide variety of ways in national literature. This ambiguity has led to various side effects. Recently in the United States, reforms collectively known as Aaron's Law were proposed as intended amendments to the Computer Fraud and Abuse Act (CFAA). Most experts expect that this change will put the brakes on the CFAA as a severe punishment policy, and result in a drop in controversial court decisions. In this study, we analyze the definitions and the penalties for hacking for each country and compare them with the national law and then make suggestions through more specific legislation. We expect it will reduce legal controversy and prevent excessive punishment. PMID:25032236

  12. Beyond Depression: Towards a Process-Based Approach to Research, Diagnosis, and Treatment.

    PubMed

    Forgeard, Marie J C; Haigh, Emily A P; Beck, Aaron T; Davidson, Richard J; Henn, Fritz A; Maier, Steven F; Mayberg, Helen S; Seligman, Martin E P

    2011-12-01

    Despite decades of research on the etiology and treatment of depression, a significant proportion of the population is affected by the disorder, fails to respond to treatment and is plagued by relapse. Six prominent scientists, Aaron Beck, Richard Davidson, Fritz Henn, Steven Maier, Helen Mayberg, and Martin Seligman, gathered to discuss the current state of scientific knowledge on depression, and in particular on the basic neurobiological and psychopathological processes at play in the disorder. These general themes were addressed: 1) the relevance of learned helplessness as a basic process involved in the development of depression; 2) the limitations of our current taxonomy of psychological disorders; 3) the need to work towards a psychobiological process-based taxonomy; and 4) the clinical implications of implementing such a process-based taxonomy.

  13. Neural mechanisms of the cognitive model of depression.

    PubMed

    Disner, Seth G; Beevers, Christopher G; Haigh, Emily A P; Beck, Aaron T

    2011-07-06

    In the 40 years since Aaron Beck first proposed his cognitive model of depression, the elements of this model--biased attention, biased processing, biased thoughts and rumination, biased memory, and dysfunctional attitudes and schemas--have been consistently linked with the onset and maintenance of depression. Although numerous studies have examined the neural mechanisms that underlie the cognitive aspects of depression, their findings have not been integrated with Beck's cognitive model. In this Review, we identify the functional and structural neurobiological architecture of Beck's cognitive model of depression. Although the mechanisms underlying each element of the model differ, in general the negative cognitive biases in depression are facilitated by increased influence from subcortical emotion processing regions combined with attenuated top-down cognitive control.

  14. Role of yoga and meditation in the context of dysfunctional self: a hypothetico-integrative approach.

    PubMed

    Singh, Yogesh; Goel, Arun; Kathrotia, Rajesh; Patil, Prashant M

    2014-01-01

    Aaron T. Beck describes habitual patterns of schemas (ie, organized patterns of thought or behavior) as vital elements of emotional and behavioral experience, whereas biased processing of information accompanies psychopathological states. In this article, the authors propose a hypothetico-integrative approach to understanding the role of yoga and meditation. This approach is based on the background of Beck's model of the psychopathology of the dysfunctional self. The authors have found that the practices common to most forms of yoga and meditation are (1) focusing of attention; (2) creating a state of relaxation; and (3) developing mindfulness through efferent attenuation, sensory attenuation, and nonanalytic attention. Biological studies of meditation and yoga have found a tendency toward use of the relaxation response, the involvement of the attentional networks, and, likely, the cingulatecortex, particularly in the process of bare attention (ie, awareness without thought). This highest level of nonjudgmental awareness may help in obtaining a better-adjusted resilient self.

  15. [A cognitive approach of the borderline personality disorder].

    PubMed

    Keegan, Eduardo

    The development of cognitive models and treatments for borderline personality disorder over the last two decades has been remarkable. This article presents the main ideas of the models developed by Aaron T. Beck and Arthur Freeman, Jeffrey Young and Marsha Linehan. These theories have generated psychotherapies that have proven their efficacy in controlled empirical studies in a difficult to treat population. The models of Beck Freeman and Young are based on the concept of schema. Linehan's dialectical behavior therapy is based on a biosocial transactional conception of the disorder. All these models emphasize the importance of negative experiences in early development. The article presents the structure of these treatments and describes their specific interventions.

  16. Cognitive theory and therapy of anxiety and depression: convergence with neurobiological findings.

    PubMed

    Clark, David A; Beck, Aaron T

    2010-09-01

    In this review paper a modified cognitive neurophysiological model of Aaron T. Beck's cognitive formulation of anxiety and depression is proposed that provides an elaborated account of the cognitive and neural mediational processes of cognitive therapy (CT). Empirical evidence consistent with this model is discussed that indicates the effectiveness of cognitive therapy could be associated with reduced activation of the amygdalohippocampal subcortical regions implicated in the generation of negative emotion and increased activation of higher-order frontal regions involved in cognitive control of negative emotion. Future cognitive neuroscience research is needed on the unique brain substrates affected by CT and their role in facilitating symptom change. This future research would have important implications for improving the efficiency and efficacy of this treatment approach.

  17. Joseph Hersey Pratt (1872-1956): An early proponent of cognitive-behavioural therapy in America.

    PubMed

    Ambrose, Charles T

    2014-02-01

    The treatment of mild psychoneuroses in America began shifting in the 1950s from Freudian psychoanalysis to various forms of psychotherapy that do not delve into patient's subconscious. Some of the new approaches were termed cognitive, behavioural or cognitive behavioural therapy and in America were practised notably by Joseph Wolpe, Albert Ellis and Aaron T Beck. Modern psychiatric literature makes little mention of two prior innovators in this area - the French neurologist Jules Dejerine and his Boston disciple Joseph H Pratt. In the early 1900s, Dejerine treated patients at La Salpêtrière in Paris using techniques adopted subsequently by Pratt during the 1930s and employed by the trio some decades later. This paper revisits the early history of psychotherapy in America and includes a brief summary of Pratt's medical career.

  18. Establishing access to technology: an evaluation and intervention model to increase the participation of children with cerebral palsy.

    PubMed

    McCarty, Elizabeth; Morress, Claire

    2009-08-01

    Children with a diagnosis of cerebral palsy often have significant physical limitations that prevent exploration and full participation in the environment. Assistive technology systems can provide opportunities for children with physical limitations to interact with their world, enabling play, communication, and daily living skills. Efficient access to and control of the technology is critical for successful use; however, establishing consistent access is often difficult because of the nature of the movement patterns exhibited by children with cerebral palsy. This article describes a 3-phase model of evaluation and intervention developed and used by Assistive Technology Services at the Aaron W. Perlman Center, Cincinnati Children's Hospital Medical Center, to establish successful access to technology systems in children with cerebral palsy.

  19. Sense of coherence and health. The construction of an amendment to Antonovsky's sense of coherence scale (SOC II).

    PubMed

    Flensborg-Madsen, Trine; Ventegodt, Søren; Merrick, Joav

    2006-06-20

    In two previous papers, we concluded that (1) the sense of coherence (SOC) scale developed by Aaron Antonovsky (1923-1994) is unable to prove the association between SOC and the physical health empirically and (2) the SOC scale is unlikely to be a fair materialization of Antonovsky's idea and, thus, unlikely to measure SOC correctly. In order to improve the scale, we developed some new questions that we suggest should be incorporated in a new questionnaire and scale (SOC II) derived directly from Antonovsky's idea and the three key explanatory concepts of SOC: comprehensibility, manageability, and meaningfulness. We hope that this new scale will demonstrate a stronger correlation between SOC and physical health.

  20. Landsat Radiometry Project

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This final report summarizes three years of work characterizing the radiometry of the Landsat 4, 5 and 7 Thematic Mappers. It is divided into six sections that are representative of the major areas of effort: 1) Internal Calibrator Lamp Monitoring; 2) Vicarious Calibration; 3) Relative Gain Analysis; 4) Outgassing; 5) Landsat 4 Absolute Calibration; and 6) Landsat 5 Scene Invariant Analysis. Each section provides a summary overview of the work that has been performed at SDSU. Major results are highlighted. In several cases, references are given to publications that have developed from this work, Several team members contributed to this report: Tim Ruggles, Dave Aaron, Shriharsha Madhavan, Esad Micijevic, Cory Mettler, and Jim Dewald. At the end of the report is a summary section.

  1. Osteopilus septentrionalis (Cuban treefrog)

    USGS Publications Warehouse

    Glorioso, Brad M.; Steece, Aaron; Lemann, Zachary K.; Lazare, Remy; Beck, James W.

    2016-01-01

    USA: LOUISIANA: St. Tammany Parish: on private property on Allen Road in Slidell (ca. 30.262°N, 89.741°W; WGS 84). 2 April 2013. Aaron Steece. Verified by Hardin Waddle. Florida Museum of Natural History (UF 177727, photo voucher). New parish record. This adult was found ca. 2 m high on a branch at the edge of a wooded area behind a house. It was photographed and released, as the species identity and significance was unknown. The origin of this individual is unknown. The homeowner stated that he bought nursery plants often, but checked them thoroughly as he put them indoors. Since this initial finding, the homeowner learned more about Cuban Treefrogs and searched for them on many occasions at this location for two years, but detected no additional Cuban Treefrogs.

  2. IES '81—Effect of the ionosphere on radiowave systems

    NASA Astrophysics Data System (ADS)

    Goodman, John M.

    A symposium entitled ‘Effect of the Ionosphere on Radiowave Systems’ was held on April 14-16, 1981, at the Ramada Inn, Old Town, Alexandria, Virginia. Over 250 participants from government, private industry, and academia were in attendance at the symposium, which was organized by John M. Goodman of the Naval Research Laboratory and Jules Aarons of the Air Force Geophysics Laboratory and was sponsored by the Office of Naval Research, NRL, and AFGL. The purpose of the symposium, as in the two previous IES conferences, held in 1975 and 1978, was to improve the information transfer between system architects, managers, and designers on the one hand and ionospheric physicists and propagation specialists on the other hand. Although the military (DoD) interest associated with various topics presented at the conference was transparent, the commercial and scientific research areas were also in evidence.

  3. The fall and rise of the history of recent chemistry.

    PubMed

    Morris, Peter J T

    2011-11-01

    This paper defines the history of recent chemistry, and then charts the disappearance of the history of recent chemistry ("how we got here" history) from general histories of chemistry by the late 1930s. It is also shown how the history of recent chemistry in the early decades of the twentieth century was very much the history of physical chemistry. The revival of the history of recent chemistry is attributed to Eduard Farber and Aaron lhde. Several attempts have been made since the early 1980s to promote the history of recent chemistry, with mixed results. The current situation is assessed, and the paper concludes with a proposal for the entrenchment of the subject.

  4. Five early accounts of phantom limb in context: Paré, Descartes, Lemos, Bell, and Mitchell.

    PubMed

    Finger, Stanley; Hustwit, Meredith P

    2003-03-01

    PHANTOM LIMB WAS described long before American physician and surgeon Silas Weir Mitchell coined the term and drew attention to the disorder in the 1860s. The early descriptions of Ambroise Paré, René Descartes, Aaron Lemos, Charles Bell, and then Mitchell of this strange consequence of amputation are presented in historical and cultural context. These five men described phantom limbs for various reasons. They also differed when it came to explaining and dealing with these illusory sensations. The rich history of phantom limbs can begin to be appreciated by viewing the contributions of these individuals in perspective and by realizing that their writings represent only a fraction of what was published about phantom limbs more than 130 years ago.

  5. Higher-Order Mixed Finite Element Methods for Time Domain Electromagnetics

    SciTech Connect

    White, D; Stowell, M; Koning, J; Rieben, R; Fisher, A; Champagne, N; Madsen, N

    2004-02-06

    This is the final report for LDRD 01-ERD-005. The Principal Investigator was Niel Madsen of the Defense Sciences Engineering Division (DSED). Collaborators included Daniel White, Joe Koning and Nathan Champagne of DSED, Mark Stowell of Center for Applications Development and Software Engineering (CADSE), and Ph.D. students Rob Rieben and Aaron Fisher at the UC Davis Department of Applied Science. It should be noted that the students were partially supported by the LLNL Student-Employee Graduate Research Fellow program. We begin with an Introduction which provides background and motivation for this research effort. Section II contains high-level description of our Approach, and Section III summarizes our key research Accomplishments. A description of the Software deliverables is provided in Section IV, and Section V includes simulation Validation and Results. It should be noted we do not get into the mathematical details in this report, rather these can be found in our publications which are listed in Section III.

  6. A NEW PATHOGENIC LEPTOSPIRA, NOT READILY CULTIVATED

    PubMed Central

    Alexander, Aaron D.; Stoenner, Herbert G.; Wood, Garnett E.; Byrne, Robert J.

    1962-01-01

    Alexander, Aaron D. (Walter Reed Army Institute of Research, Washington, D.C.), Herbert G. Stoenner, Garnett E. Wood, and Robert J. Byrne. A new pathogenic Leptospira, not readily cultivated. J. Bacteriol. 83:754–760. 1962.—A pathogenic Leptospira was isolated from water of the Grand River, (S.D.) that differed significantly from other known leptospirae in that it could not be cultivated in conventional leptospiral media. Growth was promoted in Fletcher's medium modified to contain 20% rabbit serum. The isolate, after several serial passages, was lethal for hamsters. It could not be adapted to grow in the chick embryo. Guinea pigs and calves inoculated with the isolate developed febrile and antibody responses but showed no other overt signs of disease. The strain was identified on the basis of cross-agglutination and agglutinin-adsorption tests as a new subserotype of Leptospira naam and was therefore designated as L. naam, subserotype dakotii. PMID:13860321

  7. The need for specific penalties for hacking in criminal law.

    PubMed

    Oh, Sangkyo; Lee, Kyungho

    2014-01-01

    In spite of the fact that hacking is a widely used term, it is still not legally established. Moreover, the definition of the concept of hacking has been deployed in a wide variety of ways in national literature. This ambiguity has led to various side effects. Recently in the United States, reforms collectively known as Aaron's Law were proposed as intended amendments to the Computer Fraud and Abuse Act (CFAA). Most experts expect that this change will put the brakes on the CFAA as a severe punishment policy, and result in a drop in controversial court decisions. In this study, we analyze the definitions and the penalties for hacking for each country and compare them with the national law and then make suggestions through more specific legislation. We expect it will reduce legal controversy and prevent excessive punishment.

  8. Scottish psychoanalysis: a rational religion.

    PubMed

    Miller, Gavin

    2008-01-01

    The ambition to rationally preserve a Christian religious inheritance distinctively informs Scottish psychoanalytic ideas. Scottish psychoanalysis presents the human personality as born into communion with others. The aim of therapy is to restore, preserve, and promote genuinely interpersonal relations. The Scottish psychoanalysis apparent in the work of W. R. D. Fairbairn, Ian Suttie, Hugh Crichton-Miller, and in the philosophy of John Macmurray, is exported to New Zealand, where it is promoted by the New Zealand Association of Psychotherapists. Scottish psychoanalytic ideas also remain effective in post-war Britain: the idea of communion appears in dialogue with other theories in the work of Harry Guntrip, John Macquarrie, R. D. Laing, and Aaron Esterson.

  9. Modifications to the silver physical developer.

    PubMed

    Burow, David; Seifert, Donald; Cantu, Antonio A

    2003-09-01

    The silver physical developer is currently the most successful reagent used for visualizing the water-insoluble components (e.g., lipids) of latent prints on porous surfaces. It is normally used after the amino acid visualizing reagents (e.g., ninhydrin and DFO) are used. This work found that the performance of the current formulation of silver physical developer is strongly reduced when the water used is changed from the usual distilled water to the more purified reverse osmosis/deionized (RO/DI) water. Based on numerous experiments involving the systematic variation of the component concentrations, the performance was restored and even improved by reducing the concentration of all the components (except that of the ferric salt) and by including malic acid in the formulation. These modifications resulted in a new silver physical developer formulation that performs as well as or better than the current formulation and is less expensive to make.

  10. Influence of the availability of iron during hypoxia on the genes associated with apoptotic activity and local iron metabolism in rat H9C2 cardiomyocytes and L6G8C5 skeletal myocytes.

    PubMed

    Dziegala, Magdalena; Kasztura, Monika; Kobak, Kamil; Bania, Jacek; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

    2016-10-01

    The differential availability of iron during hypoxia is presumed to affect the functioning of cardiac and skeletal myocytes. Rat H9C2 cardiomyocytes and L6G8C5 myocytes were cultured for 48 h in normoxic or hypoxic conditions at the optimal, reduced or increased iron concentration. The mRNA expression levels of markers of apoptosis [B‑cell lymphoma‑2 (Bcl2; inhibition) and Bcl‑2‑activated X protein (Bax; induction)], atrophy (Atrogin), glycolysis (pyruvate kinase 2; PKM2) and iron metabolism [transferrin receptor 1 (TfR1; iron importer), ferroportin 1 (FPN1; iron exporter), ferritin heavy chain (FTH; iron storage protein) and hepcidin (HAMP; iron regulator)] were determined using reverse transcription‑quantitative polymerase chain reaction, and cell viability was measured using an tetrazolium reduction assay. Cardiomyocytes and myocytes, when exposed to hypoxia, demonstrated an increased Bax/Bcl‑2 gene expression ratio (P<0.05). Additional deferoxamine (DFO) treatment resulted in further increases in Bax/Bcl‑2 in each cell type (P<0.001 each) and this was associated with the 15% loss in viability. The analogous alterations were observed in both cell types upon ammonium ferric citrate (AFC) treatment during hypoxia; however, the increased Bax/Bcl‑2 ratio and associated viability loss was lower compared with that in case of DFO treatment (P<0.05 each). Under hypoxic conditions, myocytes demonstrated an increased expression of PKM2 (P<0.01). Additional DFO treatment caused an increase in the mRNA expression levels of PKM2 and Atrogin‑1 (P<0.001 and P<0.05, respectively), whereas AFC treatment caused an increased mRNA expression of PKM2 (P<0.01) and accompanied decreased mRNA expression of Atrogin‑1 (P<0.05). The expression augmentation of PKM2 during hypoxia was greater upon low iron compared with that of ferric salt treatment (P<0.01). Both cell types upon DFO during hypoxia demonstrated the increased expression of TfR1

  11. Translational Treatment Paradigm for Managing Non-Unions Secondary to Radiation Injury Utilizing Adipose Derived Stem Cells and Angiogenic Therapy

    PubMed Central

    Donneys, Alexis; Blough, Jordan T.; Nelson, Noah S.; Perosky, Joseph E.; Deshpande, Sagar S.; Kang, Stephen Y.; Felice, Peter A.; Figueredo, Christian; Peterson, Jonathan R.; Kozloff, Kenneth M.; Levi, Benjamin; Chepeha, Douglas B.; Buchman, Steven R.

    2015-01-01

    Background Bony non-unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigates a novel, alternative treatment paradigm utilizing adipose derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible. Methods Rats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non-unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing. Results Significant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p<0.05). Importantly, combined therapy enabled a 65% reduction in persisting non-unions when compared to debridement alone. Conclusions We support the continued investigation of this promising combination therapy in its potential translation for the management of radiation-induced bony pathology. PMID:25917284

  12. Synthesis and protective effects of bis{4-[N,N-di-(carboxymethyl)amino]phenoxy}alkane derivatives on UVA-induced production of MMP-1 in human skin fibroblasts.

    PubMed

    Hsu, Ling-Yih; Nien, Chih-Ying; Huang, Wei-Ming; Hsu, Shou-Che; Chang, Tsu-Chung

    2014-01-01

    UV-induced matrix metalloproteinase (MMP) production is considered a cause of skin aging. In this study, a number of novel bis{4-[N,N-di-(carboxymethyl)amino]phenoxy}alkane derivatives were synthesized and evaluated as UVA-protective agents. These compounds significantly protected human dermal fibroblast (HDF) cells from UVA-induced cytotoxicity and inhibited MMP-1 activation and expression with potency comparable to desferoxamine (DFO). Promoter activity assay indicated that they inhibited MMP-1 expression at the transcriptional level. Further studies revealed that the mechanism of these compounds may include blockage of the UVA-induced activation of the p38/mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways. Together, these results suggest that further development of these compounds may be of interest.

  13. A framework for optimization and quantification of uncertainty and sensitivity for developing carbon capture systems

    DOE PAGES

    Eslick, John C.; Ng, Brenda; Gao, Qianwen; ...

    2014-12-31

    Under the auspices of the U.S. Department of Energy’s Carbon Capture Simulation Initiative (CCSI), a Framework for Optimization and Quantification of Uncertainty and Sensitivity (FOQUS) has been developed. This tool enables carbon capture systems to be rapidly synthesized and rigorously optimized, in an environment that accounts for and propagates uncertainties in parameters and models. FOQUS currently enables (1) the development of surrogate algebraic models utilizing the ALAMO algorithm, which can be used for superstructure optimization to identify optimal process configurations, (2) simulation-based optimization utilizing derivative free optimization (DFO) algorithms with detailed black-box process models, and (3) rigorous uncertainty quantification throughmore » PSUADE. FOQUS utilizes another CCSI technology, the Turbine Science Gateway, to manage the thousands of simulated runs necessary for optimization and UQ. Thus, this computational framework has been demonstrated for the design and analysis of a solid sorbent based carbon capture system.« less

  14. A framework for optimization and quantification of uncertainty and sensitivity for developing carbon capture systems

    SciTech Connect

    Eslick, John C.; Ng, Brenda; Gao, Qianwen; Tong, Charles H.; Sahinidis, Nikolaos V.; Miller, David C.

    2014-12-31

    Under the auspices of the U.S. Department of Energy’s Carbon Capture Simulation Initiative (CCSI), a Framework for Optimization and Quantification of Uncertainty and Sensitivity (FOQUS) has been developed. This tool enables carbon capture systems to be rapidly synthesized and rigorously optimized, in an environment that accounts for and propagates uncertainties in parameters and models. FOQUS currently enables (1) the development of surrogate algebraic models utilizing the ALAMO algorithm, which can be used for superstructure optimization to identify optimal process configurations, (2) simulation-based optimization utilizing derivative free optimization (DFO) algorithms with detailed black-box process models, and (3) rigorous uncertainty quantification through PSUADE. FOQUS utilizes another CCSI technology, the Turbine Science Gateway, to manage the thousands of simulated runs necessary for optimization and UQ. Thus, this computational framework has been demonstrated for the design and analysis of a solid sorbent based carbon capture system.

  15. Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation.

    PubMed

    Meo, Anna; Ruggeri, Annalisa; La Rosa, Maria A; Zanghì, Laura; Morabito, Nancy; Duca, Lorena

    2006-01-01

    In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.

  16. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    SciTech Connect

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  17. Optimization and initial evaluation of 1,2-indandione as a reagent for fingerprint detection.

    PubMed

    Gardner, Sarah J; Hewlett, Dudley F

    2003-11-01

    1,2-Indandione has been used to develop fluorescent fingerprints on porous materials such as paper. The compound reacts with amino acid residues to produce highly fluorescent fingerprint ridges. An optimized formulation and treatment protocol for using the reagent is presented here. The reagent is applied as a solution in HFE7100 containing acetic acid and ethyl acetate. Treated articles are heated at 100 degrees C for 10 min at ambient humidity and stored in the dark before recording the fingerprints using fluorescence photography or digital imaging. Photodecomposition of the fluorescent fingerprints has been observed. Storage in the dark reduces degradation, extending the lifetime of the fingerprints. Other chemical methods to stabilize the fingerprints proved unsuccessful. Comparisons of the performance of 1,2-indandione with DFO in CFC113 performed on a limited range of substrates indicated that the reagent might be an effective method for the development of latent fingerprints despite the new reagent producing less intense fluorescence.

  18. Longitude dependent response of the GPS derived ionospheric ROTI to geomagnetic storms

    NASA Astrophysics Data System (ADS)

    Tanna, H. J.; Pathak, K. N.

    2014-08-01

    The local time dependent effects of geomagnetic storm on the ionospheric TEC and Rate of change of TEC Index (ROTI) are studied here using the GPS data for four different low latitude stations: Ogaswara, Japan (24.29 °N, 153.91 °E; Geomagnetic: 17.21 °N, 136.16 °W); Surat, India (21.16 °N, 72.78 °E; Geomagnetic: 12.88 °N, 146.91 °E); Bogota, Colombia (4.64 °N, -74.09 °E; Geomagnetic: 14.42 °N, 1.67 °W); and Kokee park Waimea, Hawaii, US (22.12 °N, -159.67 °E; Geomagnetic: 22.13 °N, 91.19 °W). The solar wind velocity and geomagnetic indices: Dst, Kp and IMF Bz are utilized to validate the geomagnetic storms registered during the years 2011 and 2012. Using the GPS based TEC data and computed values of ROTI, the storm induced ionospheric irregularities generation and inhibition has been studied for all stations. The present study suggests that, the F-region irregularities of a scale length of few kilometers over the magnetic equator are locally affected by geomagnetic storms. This study also shows a good agreement (70-84 %) with the Aaron's criteria (Aarons, Radio Sci., 26:1131-1149, 1991; Biktash, Ann. Geophys., 19:731-739, 2004) as significant absence and enhancement of ROTI was found to be influenced by the local time of the negative peak of Dst index association.

  19. Convergent Close-Coupling Approach to Electron-Atom Collisions

    NASA Technical Reports Server (NTRS)

    Bray, Igor; Stelbovics, Andris

    2007-01-01

    It was with great pleasure and honour to accept the invitation to make a presentation at the symposium celebrating the life-long work of Aaron Temkin and Richard Drachman. The work of Aaron Temkin was particularly influential on our own during the development of the CCC method for electron-atom collisions. There are a number of key problems that need to be dealt with when developing a general computational approach to such collisions. Traditionally, the electron energy range was subdivided into the low, intermediate, and high energies. At the low energies only a finite number of channels are open and variational or close-coupling techniques could be used to obtain accurate results. At high energies an infinite number of discrete channels and the target continuum are open, but perturbative techniques are able to yield accurate results. However, at the intermediate energies perturbative techniques fail and computational approaches need to be found for treating the infinite number of open channels. In addition, there are also problems associated with the identical nature of electrons and the difficulty of implementing the boundary conditions for ionization processes. The beauty of the Temkin-Poet model of electron-hydrogen scattering is that it simplifies the full computational problem by neglecting any non-zero orbital angular momenta in the partial-wave expansion, without loosing the complexity associated with the above-mentioned problems. The unique nature of the problem allowed for accurate solution leading to benchmark results which could then be used to test the much more general approaches to electron-atom collision problems. The immense value of the Temkin-Poet model is readily summarised by the fact that the initial papers of Temkin and Poet have been collectively cited around 250 times to date and are still being cited in present times. Many of the citations came from our own work during the course of the development of the CCC method, which we now describe.

  20. The characteristics of suicide attempts based on the suicidal intent scale scores.

    PubMed

    Polewka, Andrzej; Mikołaszek-Boba, Magdalena; Chrostek Maj, Jan; Groszek, Barbara

    2005-01-01

    The aim of the work was to present the characteristics of suicide attempts, distinguished on the basis of the scores in the Suicidal Intent Scale questionnaire (SIS), created by Aaron Beck, professor of psychiatry from Philadelphia. The group examined comprised 238 patients (63 males and 175 females) hospitalised in the Department of Clinical Toxicology CMUJ in Kraków in the years 2000-2001, after a suicidal self-intoxication with xenobiotics. The examination was conducted by means of the Suicidal Intent Scale (SIS)--a psychological test created by Aaron Beck. In the case of about 65% of the patients examined, their suicide attempts most frequently were acts of impulsive behaviour, rarely planned for longer than three hours before the realization and usually made in another person's presence or in a situation in which another person's intervention was highly probable. Such attempts had the character of "a cry for help", and were aimed at effecting some change or at manipulating the environment. Nevertheless, the patients acted in a conviction that their act was a serious attempt at ending life, and, most frequently, they maintained such opinions during the examination. On the other hand, they rarely expressed further suicidal intents, and more frequently accepted the fact that their lives had been saved. By contrast, the remaining 35% of the patients examined had attempted suicide with the evident intention to kill themselves; they had taken full precautions against being discovered and had planned suicide carefully to eliminate the smallest possibility of intervention. In the majority of cases, they still maintained the wish to die after the attempt. As the results of the examination indicate, the Suicidal Intent Scale, and, especially, the Precautions subscale, point at the important aspect of suicidal intentions, which, being of vital importance for the diagnostic purposes and suicide prevention, requires further investigation.

  1. Oxidant-induced autophagy and ferritin degradation contribute to epithelial–mesenchymal transition through lysosomal iron

    PubMed Central

    Sioutas, Apostolos; Vainikka, Linda K; Kentson, Magnus; Dam-Larsen, Sören; Wennerström, Urban; Jacobson, Petra; Persson, Hans Lennart

    2017-01-01

    Purpose Transforming growth factor (TGF)-β1 triggers epithelial–mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome. Materials and methods EMT, H-ferritin, and autophagy were evaluated in TGF-β1-stimulated A549 human lung epithelial cells cultured in vitro using Western blotting, with the additional morphological assessment of EMT. By using immunofluorescence and flow cytometry, lysosomes and ROS were assessed by acridine orange and 6-carboxy-2′,7′-dichlorodihydrofluorescein acetate assays, respectively. Results TGF-β1-stimulated cells demonstrated a loss of H-ferritin, which was prevented by the antioxidant N-acetyl-L-cysteine (NAC) and inhibitors of lysosomal degradation. TGF-β1 stimulation generated ROS and autophagosome formation and led to EMT, which was further promoted by the additional ROS-generating cytokine, tumor necrosis factor-α. Lysosomes of TGF-β1-stimulated cells were sensitized to oxidants but also completely protected by lysosomal loading with dextran-bound deferoxamine (DFO). Autophagy and EMT were prevented by NAC, DFO, and inhibitors of autophagy and lysosomal degradation. Conclusion The findings of this study support the role of enhanced autophagic degradation of H-ferritin as a mechanism for increasing the vulnerability of lysosomes to iron-driven oxidant injury that triggers further autophagy during EMT. This study proposes that lysosomal leakage is a novel pathway of TGF-β1-induced EMT that may be prevented by iron-chelating drugs that target the lysosome.

  2. Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanisms

    SciTech Connect

    Imrich, Amy; Ning Yaoyu; Lawrence, Joy; Coull, Brent; Gitin, Elena; Knutson, Mitchell; Kobzik, Lester . E-mail: lkobzik@hsph.harvard.edu

    2007-02-01

    Alveolar macrophages (AMs) primed with LPS and treated with concentrated ambient air particles (CAPs) showed enhanced release of tumor necrosis factor (TNF) and provide an in vitro model for the amplified effects of air pollution particles seen in people with preexisting lung disease. To investigate the mechanism(s) by which CAPs mediate TNF release in primed rat AMs, we first tested the effect of a panel of antioxidants. N-Acetyl-L-cysteine (20 mM), dimethyl thiourea (20 mM) and catalase (5 {mu}M) significantly inhibited TNF release by primed AMs incubated with CAPs. Conversely, when LPS-primed AMs were treated with CAPs in the presence of exogenous oxidants (H{sub 2}O{sub 2} generated by glucose oxidase, 10 {mu}M/h), TNF release and cell toxicity was significantly increased. The soluble fraction of CAPs suspensions caused most of the increased bioactivity in the presence of exogenous H{sub 2}O{sub 2}. The metal chelator deferoxamine (DFO) strongly inhibited the interaction of the soluble fraction with H{sub 2}O{sub 2} but had no effect on the bioactivity of the insoluble CAPs fraction. We conclude that CAPs can mediate their effects in primed AMs by acting on oxidant-sensitive cytokine release in at least two distinct ways. In the primed cell, insoluble components of PM mediate enhanced TNF production that is H{sub 2}O{sub 2}-dependent (catalase-sensitive) yet independent of iron (DFO-insensitive). In the presence of exogenous H{sub 2}O{sub 2} released by AMs, PMNs, or other lung cells within an inflamed alveolar milieu, soluble iron released from air particles can also mediate cytokine release and cell toxicity.

  3. Flood mapping by combining the strengths of optical and Sentinel active radar remote sensing

    NASA Astrophysics Data System (ADS)

    Winsemius, H. C.; Brakenridge, G. R.; Westerhoff, R.; Huizinga, J.; Villars, N.; Bishop, C.

    2012-04-01

    Flood mapping with remote sensing plays an important role in large scale disaster management procedures. For this purpose, the Dartmouth Flood Observatory (DFO) gained experience since 1993 with the production of flood maps from optical satellite imagery and has currently established, together with NASA collaborators, a fully automated, global, near real-time service. Another consortium is also presently working on an automated, near real-time, global flood mapping procedure called the 'Global Flood Observatory' (GFO), which will make use of high resolution Sentinel data. The procedure is currently tested on Envisat active radar (ASAR) imagery. Both the DFO and GFO projects provide open data output of their data and maps. The optical and radar approaches to flood mapping each have advantages and suffer from shortcomings. Optical remote sensing via the U.S. MODIS and VIIRS sensors is constrained by cloud cover but can attain a high revisit frequency (>2 /day), whereas the Envisat ASAR is not affected by cloud cover, but uses a lower revisit frequency (generally once/3 days, depending on the location). In this contribution, we demonstrate the combination of both approaches into one flood mapping result. This results in improved flood mapping in a case study over the Chao Phraya basin (Bangkok surroundings) during the recent October-November 2011 extreme flooding. The combined map shows that during overpass, ASAR reveals flooded regions over cloud-obscured areas, which clearly follow elevated features in the landscape such as roads, embankments and railways. Meanwhile, the high frequency of delivery of the optical information ensures timely information. Also, the quite different water classification methods used for the optical and ASAR data sources show good agreement and have been successfully merged into one GIS data product. This can also be automatically generated and disseminated on a global basis.

  4. The Eltrombopag antitumor effect on hepatocellular carcinoma

    PubMed Central

    KUROKAWA, TOMOHIRO; MURATA, SOICHIRO; ZHENG, YUN-WEN; IWASAKI, KENICHI; KOHNO, KEISUKE; FUKUNAGA, KIYOSHI; OHKOHCHI, NOBUHIRO

    2015-01-01

    Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC. Eltrombopag (EP), a TPO receptor agonist, has been reported to have antitumor effects against certain cancers, despite their lack of TPO receptor expression. We hypothesized that EP may possess antitumor activity against HCC in addition to its ability to suppress hepatic fibrosis by increasing the platelet count. In the present study, the antitumor activity of EP was examined by assessing the inhibition of cell proliferation and then ascertaining the ability of iron supplementation to reverse these effects in HepG2, Hep3B and Huh7 cells. In addition, a cell cycle assay was performed using flow cytometry, and signal transduction was evaluated by analyzing cell cycle-related protein expression. The results of EP were compared with those of the most common iron chelator, deferoxamine (DFO). The combined effect of EP and sorafenib was also assessed. The results revealed that EP exerts antitumor activity in HCC that is mediated by the modulation of intracellular iron content. EP suppressed the expression of the cell cycle-related protein cyclin D1 and elicited cell cycle arrest in the G0/G1 phase. The activity of EP was comparable to that of DFO in HCC, and EP did not compete with sorafenib at low concentrations. In conclusion, our findings suggest that EP is a good candidate chemotherapeutic agent for the treatment of HCC in patients with LC and thrombocytopenia. PMID:26397763

  5. The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings.

    PubMed

    Chazan, J A; Libbey, N P; London, M R; Pono, L; Abuelo, J G

    1991-02-01

    Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis.

  6. Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer

    PubMed Central

    Houghton, Jacob L.; Zeglis, Brian M.; Abdel-Atti, Dalya; Aggeler, Robert; Sawada, Ritsuko; Agnew, Brian J.; Scholz, Wolfgang W.; Lewis, Jason S.

    2015-01-01

    Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs (ssDFO-5B1, ssFL-5B1, and ssdual-5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9-positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The ssdual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation. PMID:26668398

  7. Modular strategy for the construction of radiometalated antibodies for positron emission tomography based on inverse electron demand Diels-Alder click chemistry.

    PubMed

    Zeglis, Brian M; Mohindra, Priya; Weissmann, Gabriel I; Divilov, Vadim; Hilderbrand, Scott A; Weissleder, Ralph; Lewis, Jason S

    2011-10-19

    A modular system for the construction of radiometalated antibodies was developed based on the bioorthogonal cycloaddition reaction between 3-(4-benzylamino)-1,2,4,5-tetrazine and the strained dienophile norbornene. The well-characterized, HER2-specific antibody trastuzumab and the positron emitting radioisotopes (64)Cu and (89)Zr were employed as a model system. The antibody was first covalently coupled to norbornene, and this stock of norbornene-modified antibody was then reacted with tetrazines bearing the chelators 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA) or desferrioxamine (DFO) and subsequently radiometalated with (64)Cu and (89)Zr, respectively. The modification strategy is simple and robust, and the resultant radiometalated constructs were obtained in high specific activity (2.7-5.3 mCi/mg). For a given initial stoichiometric ratio of norbornene to antibody, the (64)Cu-DOTA- and (89)Zr-DFO-based probes were shown to be nearly identical in terms of stability, the number of chelates per antibody, and immunoreactivity (>93% in all cases). In vivo PET imaging and acute biodistribution experiments revealed significant, specific uptake of the (64)Cu- and (89)Zr-trastuzumab bioconjugates in HER2-positive BT-474 xenografts, with little background uptake in HER2-negative MDA-MB-468 xenografts or other tissues. This modular system-one in which the divergent point is a single covalently modified antibody stock that can be reacted selectively with various chelators-will allow for both greater versatility and more facile cross-comparisons in the development of antibody-based radiopharmaceuticals.

  8. Acute BMP2 upregulation following induction of ischemic osteonecrosis in immature femoral head.

    PubMed

    Kamiya, Nobuhiro; Shafer, Sasha; Oxendine, Ila; Mortlock, Douglas P; Chandler, Ronald L; Oxburgh, Leif; Kim, Harry K W

    2013-03-01

    Juvenile ischemic osteonecrosis of the femoral head (IOFH) is one of the most serious hip conditions causing the femoral head deformity. Little is known about BMP signaling following ischemic osteonecrosis. In this study, we found acute BMP2 upregulation in the femoral head cartilage 24h after ischemic induction using our immature pig IOFH model. Similarly, in our ischemic osteonecrosis mouse model, BMP2 expression and BMP signaling were enhanced in the articular cartilage surrounding the necrotic bone. BMP2 was increased in cartilage explants and primary chondrocytes under hypoxia (1% O(2)) compared with normoxia (21% O(2)). Addition of the hypoxia inducible factor 1 (HIF1) activator DFO significantly increased BMP2 while HIF1 silencing (siHIF1) only partially reduced BMP2, suggesting other mechanisms of BMP2 upregulation being present. Hypoxia is known to induce the production of free oxygen radicals, which are converted to hydrogen peroxide (H(2)O(2)) by superoxide dismutase 2 (SOD2). As an alternative mechanism, we investigated the effect of H(2)O(2)/SOD2 production on BMP2 upregulation. Chondrocytes produced more H(2)O(2) under hypoxia than normoxia. H(2)O(2) addition to the chondrocyte culture also significantly increased BMP2 expression. SOD2 was also dramatically increased in the ischemic pig cartilage at 24h following surgery and in primary chondrocytes/cartilage explants culture under hypoxia. SOD2 protein addition to the chondrocyte culture significantly increased BMP2. Moreover, DFO significantly increased SOD2 while HIF1 silencing only partially reduced SOD2. These results suggest that the acute BMP2 response of chondrocytes to ischemic osteonecrosis is more dominantly through the H(2)O(2) production and only partly through the HIF1 pathway.

  9. Iron depletion in HCT116 cells diminishes the upregulatory effect of phenethyl isothiocyanate on heme oxygenase-1.

    PubMed

    Bolloskis, Michael P; Carvalho, Fabiana P; Loo, George

    2016-04-15

    Some of the health-promoting properties of cruciferous vegetables are thought to be partly attributed to isothiocyanates. These phytochemicals can upregulate the expression of certain cytoprotective stress genes, but it is unknown if a particular nutrient is involved. Herein, the objective was to ascertain if adequate iron is needed for enabling HCT116 cells to optimally express heme oxygenase-1 (HO-1) when induced by phenethyl isothiocyanate (PEITC). PEITC increased HO-1 expression and also nuclear translocation of Nrf2, which is a transcription factor known to activate the HO-1 gene. However, in HCT116 cells that were made iron-deficient by depleting intracellular iron with deferoxamine (DFO), PEITC was less able to increase HO-1 expression and nuclear translocation of Nrf2. These suppressive effects of DFO were overcome by replenishing the iron-deficient cells with the missing iron. To elucidate these findings, it was found that PEITC-induced HO-1 upregulation can be inhibited with thiol antioxidants (glutathione and N-acetylcysteine). Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin) and a superoxide scavenger (Tiron) each inhibited PEITC-induced HO-1 upregulation. In doing so, diphenyleneiodonium was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf2. Collectively, the results imply that the HO-1 upregulation by PEITC involves an iron-dependent, oxidant signaling pathway. Therefore, it is concluded that ample iron is required to enable PEITC to fully upregulate HO-1 expression in HCT116 cells. As such, it is conceivable that iron-deficient individuals may not reap the full health benefits of eating PEITC-containing cruciferous vegetables that via HO-1 may help protect against multiple chronic diseases.

  10. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    PubMed

    Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li

    2015-01-01

    Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress.

  11. Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for 89Zr4+ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

    PubMed Central

    N.Tinianow, Jeff; Pandya, Darpan N.; Pailloux, Sylvie L.; Ogasawara, Annie; Vanderbilt, Alexander N.; Gill, Herman S.; Williams, Simon-P.; Wadas, Thaddeus J.; Magda, Darren; Marik, Jan

    2016-01-01

    A novel octadentate 3-hydroxypyridin-2-one (2,3-HOPO) based di-macrocyclic ligand was evaluated for chelation of 89Zr; subsequently, it was used as a bi-functional chelator for preparation of 89Zr-labeled antibodies. Quantitative chelation of 89Zr4+ with the octadentate ligand forming 89ZrL complex was achieved under mild conditions within 15 minutes. The 89Zr-complex was stable in vitro in presence of DTPA, but a slow degradation was observed in serum. In vivo, the hydrophilic 89Zr-complex showed prevalently renal excretion; and an elevated bone uptake of radioactivity suggested a partial release of 89Zr4+ from the complex. The 2,3-HOPO based ligand was conjugated to the monoclonal antibodies, HER2-specific trastuzumab and an isotypic anti-gD antibody, using a p-phenylene bis-isothiocyanate linker to yield products with an average loading of less than 2 chelates per antibody. Conjugated antibodies were labeled with 89Zr under mild conditions providing the PET tracers in 60-69% yield. Despite the limited stability in mouse serum; the PET tracers performed very well in vivo. The PET imaging in mouse model of HER2 positive ovarian carcinoma showed tumor uptake of 89Zr-trastuzumab (29.2 ± 12.9 %ID/g) indistinguishable (p = 0.488) from the uptake of positive control 89Zr-DFO-trastuzumab (26.1 ± 3.3 %ID/g). In conclusion, the newly developed 3-hydroxypyridin-2-one based di-macrocyclic chelator provides a viable alternative to DFO-based heterobifunctional ligands for preparation of 89Zr-labeled monoclonal antibodies for immunoPET studies. PMID:26941844

  12. Facilitation of human osteoblast apoptosis by sulindac and indomethacin under hypoxic injury.

    PubMed

    Liu, Cheng; Tsai, An-Ly; Chen, Yen-Chu; Fan, Shih-Chen; Huang, Chun-Hsien; Wu, Chia-Ching; Chang, Chih-Han

    2012-01-01

    Hypoxic-ischemia injury occurs after trauma causes consequential bone necrosis. Non-steroid anti-inflammatory drugs (NSAIDs) are frequently used in orthopedic clinics for pain relief. However, the underlying mechanism and outcome for usage of NSAIDs is poorly understood. To investigate the damage and loss of osteoblast function in hypoxia, two hypoxia mimetics, cobalt chloride (CoCl(2)) and desferrioxamine (DFO), were used to create an in vitro hypoxic microenvironment. The cell damage was observed by decreases of cell viability and increases in cyclooxygenase-2 and cleaved poly(ADP-ribose) polymerase (PARP). Cell apoptosis was confirmed by WST-1 cytotoxic assays and flow cytometry. The functional expression of osteoblast in alkaline phosphatase (ALP) activity was significantly decreased by CoCl(2) and inhibited when treated with DFO. To simulate the use of NSAID after hypoxic injury, four types of anti-inflammatory drugs, sulindac sulfide (SUL), indomethacin (IND), aspirin (Asp), and sodium salicylate (NaS), were applied to osteoblasts after 1 h of hypoxia mimetic treatment. SUL and IND further enhanced cell death after hypoxia. ALP activity was totally abolished in hypoxic osteoblasts under IND treatment. Facilitation of osteoblast apoptosis occurred regardless of IND dosage under hypoxic conditions. To investigate osteoblast in vivo, local hypoxia was created by fracture of tibia and then treated the injured mice with IND by oral feeding. IND-induced osteoblast apoptosis was confirmed by positive staining of TUNEL assay in fractured mice. Significant delay of fracture healing in bone tissue was also observed with the treatment of IND. These results provide information pertaining to choosing appropriate anti-inflammatory drugs for orthopedic patients.

  13. The role of HIF in cobalt-induced ischemic tolerance.

    PubMed

    Jones, S M; Novak, A E; Elliott, J P

    2013-11-12

    Understanding the endogenous survival pathways induced by ischemic tolerance may yield targets for neuroprotection from stroke. One well-studied pathway reported to be evoked by preconditioning stimuli is the transcription factor HIF (hypoxia-inducible factor). However, whether HIF induction by ischemic insults is neuroprotective or toxic is still unclear. We examined the ability of three prolyl-hydroxylase inhibitors, which induce HIF, to protect hippocampal cultures from oxygen-glucose deprivation. Hippocampal cultures were exposed to ischemic preconditioning or various concentrations of cobalt chloride, deferoxamine (DFO) or dimethyloxylalyglycine (DMOG), prior to lethal oxygen-glucose deprivation (OGD). Cell survival of neurons and astrocytes was determined with dual-label immunocytochemistry. The induction of HIF targets was assessed in mixed as well as astrocyte-enriched cultures. Ischemic preconditioning, as well as low concentrations of cobalt and DFO, enhanced the survival of neurons following OGD. However, DMOG exacerbates OGD-induced neuronal death. At low concentrations, all three prolyl-hydroxylase (PHD) inhibitors increased the survival of astrocytes. Neuroprotective concentrations of cobalt induced the transcription of the cytokine erythropoietin (EPO) in astrocyte cultures. In addition, pretreatment with recombinant human erythropoietin (rH-EPO) also protected neurons from OGD. Our data suggest that HIF-induced EPO, released from astrocytes, protects neurons from OGD. However, the three PHD inhibitors each exhibited different neuroprotective profiles at low concentrations, suggesting that not all PHD inhibitors are created equal. The protective effects at low doses is reminiscent of HIF involvement in ischemic tolerance, in which sub-lethal insults induce HIF pathways resulting in neuroprotection, whereas the high-dose toxicity suggests that over-activation of HIF is not always protective. Therefore, the choice of inhibitor and dose may determine

  14. Iron depletion increases manganese uptake and potentiates apoptosis through ER stress

    PubMed Central

    Seo, Young Ah; Li, Yuan; Wessling-Resnick, Marianne

    2013-01-01

    Iron deficiency is a risk factor for manganese (Mn) accumulation. Excess Mn promotes neurotoxicity but the mechanisms involved and whether iron depletion might affect these pathways is unknown. To study Mn intoxication in vivo, iron deficient and control rats were intranasally instilled with 60 mg MnCl2/kg over 3 weeks. TUNEL staining of olfactory tissue revealed that Mn exposure induced apoptosis and that iron deficiency potentiated this effect. In vitro studies using the dopaminergic SH-SY5Y cell line confirmed that Mn-induced apoptosis was enhanced by iron depletion using the iron chelator desferrioxamine. Mn has been reported to induce apoptosis through endoplasmic reticulum stress. In SH-SY5Y cells, Mn exposure induced the ER stress genes glucose regulated protein 94 (GRP94) and C/EBP homologous protein (CHOP). Increased phosphorylation of the eukaryotic translation initiation factor 2α (phospho-eIF2α) was also observed. These effects were accompanied by the activation of ER resident enzyme caspase-12, and the downstream apoptotic effector caspase-3 was also activated. All of the Mn-induced responses were enhanced by DFO treatment. Inhibitors of ER stress and caspases significantly blocked Mn-induced apoptosis and its potentiation by DFO, indicating that ER stress and subsequent caspase activation underlie cell death. Taken together, these data reveal that Mn induces neuronal cell death through ER stress and the UPR response pathway and that this apoptotic effect is potentiated by iron deficiency most likely through upregulation of DMT1. PMID:23764342

  15. HIF and reactive oxygen species regulate oxidative phosphorylation in cancer.

    PubMed

    Hervouet, Eric; Cízková, Alena; Demont, Jocelyne; Vojtísková, Alena; Pecina, Petr; Franssen-van Hal, Nicole L W; Keijer, Jaap; Simonnet, Hélène; Ivánek, Robert; Kmoch, Stanislav; Godinot, Catherine; Houstek, Josef

    2008-08-01

    A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.

  16. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload

    PubMed Central

    Kattamis, Antonis; Cappellini, M. Domenica; El-Beshlawy, Amal; Origa, Raffaella; Elalfy, Mohsen; Kilinç, Yurdanur; Perrotta, Silverio; Karakas, Zeynep; Viprakasit, Vip; Habr, Dany; Constantinovici, Niculae; Shen, Junwu; Porter, John B.

    2015-01-01

    Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (−52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227. PMID:25934475

  17. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID:26893541

  18. Dissemination of satellite-based river discharge and flood data

    NASA Astrophysics Data System (ADS)

    Kettner, A. J.; Brakenridge, G. R.; van Praag, E.; de Groeve, T.; Slayback, D. A.; Cohen, S.

    2014-12-01

    In collaboration with NASA Goddard Spaceflight Center and the European Commission Joint Research Centre, the Dartmouth Flood Observatory (DFO) daily measures and distributes: 1) river discharges, and 2) near real-time flood extents with a global coverage. Satellite-based passive microwave sensors and hydrological modeling are utilized to establish 'remote-sensing based discharge stations', and observed time series cover 1998 to the present. The advantages over in-situ gauged discharges are: a) easy access to remote or due to political reasons isolated locations, b) relatively low maintenance costs to maintain a continuous observational record, and c) the capability to obtain measurements during floods, hazardous conditions that often impair or destroy in-situ stations. Two MODIS instruments aboard the NASA Terra and Aqua satellites provide global flood extent coverage at a spatial resolution of 250m. Cloud cover hampers flood extent detection; therefore we ingest 6 images (the Terra and Aqua images of each day, for three days), in combination with a cloud shadow filter, to provide daily global flood extent updates. The Flood Observatory has always made it a high priority to visualize and share its data and products through its website. Recent collaborative efforts with e.g. GeoSUR have enhanced accessibility of DFO data. A web map service has been implemented to automatically disseminate geo-referenced flood extent products into client-side GIS software. For example, for Latin America and the Caribbean region, the GeoSUR portal now displays current flood extent maps, which can be integrated and visualized with other relevant geographical data. Furthermore, the flood state of satellite-observed river discharge sites are displayed through the portal as well. Additional efforts include implementing Open Geospatial Consortium (OGC) standards to incorporate Water Markup Language (WaterML) data exchange mechanisms to further facilitate the distribution of the satellite

  19. Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons.

    PubMed

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J

    2015-07-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons.

  20. Assessment of trophic status in Changjiang (Yangtze) River estuary

    NASA Astrophysics Data System (ADS)

    Wang, Baodong

    2007-07-01

    The integrated methodology for the assessment of estuarine trophic status (ASSETS), which was extended and refined from the United States National Estuarine Eutrophication Assessment (NEEA), is a multi-parameter assessment system and has been widely used in eutrophication assessment in estuarine and coastal waters. The ASSETS was applied to evaluate the trophic status of the Changjiang (Yangtze) River estuary, one of the largest estuaries in the world. The following main results were obtained: (i) The estuarine export potential is “moderate susceptibility” due to the “moderate” dilution potential and “moderate” flushing potential; (ii) The overall human influence (OHI) index classified the impact of nutrients in the system as “high” due to the high level of nutrient discharge by the river which channels anthropogenic impacts in the catchments to the estuarine system; (iii) The overall eutrophic condition (OEC) in the estuary was classified into the “high” category due to frequent occurrence of nuisance and toxic algal blooms in the mixing and seawater zones; (iv) Since the nutrient loadings (e.g., DIN) in the river is expected to continue to increase in the near future following the population increase and rapid economic growth throughout the drainage basin, the nutrient-related symptoms in the estuary are likely to substantially worsen, which leads to the “worsen high” category for the definition of future outlook (DFO). The combinations of the three components (i.e., OHI, OEC, and DFO) lead to an overall grade as “bad” for the trophic status in the Changjiang River estuary.

  1. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre.

    PubMed

    Gamberini, Maria Rita; De Sanctis, Vincenzo; Gilli, Giuseppe

    2008-10-01

    273 patients with thalassaemia major followed from diagnosis in the Ferrara Centre were divided into 3 cohorts (C) according to the year of birth (C1=1954-1964, 85 patients; C2=1965-1974, 129 patients; C3=1975-2001, 59 patients) in order to study the trends of endocrine complications. Menarche occurred in 52 out of 112 patients (46%), without significant differences among the 3 groups, at the mean age of 13.9+/-1.4 years. Sixty-five percent of these patients had secondary amenorrhoea at the mean age of 18.8+/-3.7 years. In males complete pubertal development occurred in 48% of patients (C1:31%, C2: 44%, C3: 63%, p<0.05) followed by secondary hypogonadism in 24% of patients above 21 years of age. Primary (80%) and central 20%) hypothyroidism were diagnosed in 31% of patients (C1: 55%, C2: 31.5%, C3: 13.4%, p<0.05), diabetes mellitus (DM) in 17% of patients (C1: 28.6%, C2: 17.2%, C3: 3.4%, p<0.05), and hypoparathyroidism in 10.6% of cases (C1: 18.7%, C2: 10.1%, C3: 3.4%, p<0.05). No difference was found in patient mean age of diagnosis of hypothyroidism, DM or hypoparathyroidism (20.4+/-8.2 years, 19+/-5 yrs and 18.5+/-5.8 yrs respectively) but in all three groups age at diagnosis significantly increased over time (hypothyroidism and DM: p<0.001; hypoparathyroidism: p<0.01). Over time the prevalence of hypothyroidism, diabetes mellitus and hypoparathyroidism increased to 24.4%, 14.7%, and 6.7%, respectively, at the time of the study. Incidences peaked in the early 1980's, and declined in the following years (primary hypothyroidism from 6.5% in 1981 to 0.9% in 2007, p<0.01; DM from 3.9% in 1986 to 0.8% in 2007, p<0.05; hypoparathyroidism 2.4% in 1984 to 0% in 2007, p<0.01) and correlated with the decrease in annual mean serum ferritin levels in all patients (p<0.001). The main risk factors associated with endocrine complications were high serum ferritin levels, poor compliance with desferioxamine (DFO) therapy, early onset of transfusion therapy (only for hypogonadism

  2. Siderophore Promoted Dissolution of a Series of Mn-Substituted Goethites

    NASA Astrophysics Data System (ADS)

    Holmstrom, S. J.; Sposito, G.

    2005-12-01

    The presence of organic ligands, like siderophores, can strongly influence mineral dissolution. Recent research suggests that at least some siderophores enhance mineral dissolution by formation of surface complexes with Fe and Mn. The impact of biogeochemical weathering caused by exudates of plants, fungi and bacteria containing siderophores has been discussed. We have studied the dissolution kinetics of Mn-substituted goethites (mol % Mn < 11) in the presences of 80 μM desferrioxamine B (DFO-B), a common and well-studied hydroxamate siderophore that has been identified in both terrestrial and marine environments and which forms very stable 1:1 complexes with Fe(III) or Mn(III). (The stability constants at I = 0.1 are 1030.6 and 1028.3, respectively.) A series of Mn-substituted goethites (α-MnxFe1-xOOH) were synthesized from ferrihydrite in the presence of Mn(II) in alkaline media. The Fe(III) in octahedral positions in the mineral structure was partially replaced by Mn, which was confirmed visually by the change to darker color when the content of Mn increased and proved by infra-red spectroscopy and X-ray diffraction studies of the samples. Substitution of Fe in the goethite by Mn caused a change in the cell dimensions. The calculated unit cell edge lengths a and c decreased, while b increased, for the Mn-goethites compared to pure goethite. The difference of the unit cell parameters between the pure goethite and the Mn-substituted goethites increased with increased Mn content, providing further confirmation that Fe had been substituted by Mn incorporated into the goethite structure. X-ray absorption near-edge structure spectroscopy analysis of the Mn-substituted goethites showed that the oxidation state of Mn in the samples was, as expected, Mn(III), even when Mn-goethites were prepared from Mn(II) solutions. Both SEM and TEM micrographs showed that the Mn-substituted goethite crystals had the same acicular shape as pure goethite. The specific surface area

  3. The metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), inhibits stress-induced autophagy in cancer cells.

    PubMed

    Sahni, Sumit; Bae, Dong-Hun; Lane, Darius J R; Kovacevic, Zaklina; Kalinowski, Danuta S; Jansson, Patric J; Richardson, Des R

    2014-04-04

    N-myc downstream regulated gene 1 (NDRG1) is a potent metastasis suppressor with an undefined role in the stress response. Autophagy is a pro-survival pathway and can be regulated via the protein kinase-like endoplasmic reticulum kinase (PERK)/eIF2α-mediated endoplasmic reticulum (ER) stress pathway. Hence, we investigated the role of NDRG1 in stress-induced autophagy as a mechanism of inhibiting metastasis via the induction of apoptosis. As thiosemicarbazone chelators induce stress and up-regulate NDRG1 to inhibit metastasis, we studied their effects on the ER stress response and autophagy. This was important to assess, as little is understood regarding the role of the stress induced by iron depletion and its role in autophagy. We observed that the chelator, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which forms redox-active iron and copper complexes, effectively induced ER stress as shown by activation of the PERK/eIF2α pathway. Dp44mT also increased the expression of the autophagic marker, LC3-II, and this was dependent on activation of the PERK/eIF2α axis, as silencing PERK prevented LC3-II accumulation. The effect of Dp44mT on LC3-II expression was at least partially due to iron-depletion, as this effect was also demonstrated with the classical iron chelator, desferrioxamine (DFO), and was not observed for the DFO-iron complex. NDRG1 overexpression also inhibited basal autophagic initiation and the ER stress-mediated autophagic pathway via suppression of the PERK/eIF2α axis. Moreover, NDRG1-mediated suppression of the pro-survival autophagic pathway probably plays a role in its anti-metastatic effects by inducing apoptosis. In fact, multiple pro-apoptotic markers were increased, whereas anti-apoptotic Bcl-2 was decreased upon NDRG1 overexpression. This study demonstrates the role of NDRG1 as an autophagic inhibitor that is important for understanding its mechanism of action.

  4. Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy

    PubMed Central

    De Sanctis, Vincenzo; Elsedfy, Heba; Soliman, Ashraf T.; Elhakim, Ihab Zaki; Kattamis, Christos; Soliman, Nada A.; Elalaily, Rania

    2016-01-01

    Introduction It is well known that the older generation of adult TM patients has a higher incidence of morbidities and co-morbidities. At present, little information is available on adult TM patients with multiple endocrine complications (MEC). The main objectives of this longitudinal retrospective survey were: 1) to establish the incidence and progression of MEC (3 or more) in TM patients; 2) to compare the clinical, laboratory and imaging data to a sex and age-matched group of TM patients without MEC; 3) to assess the influence of iron overload represented by serum ferritin (peak and mean annual value at the last endocrine observation). Patients and methods The study was started in January 1974 and was completed by the same physician at the end of December 2015. The registry database of the regularly followed TM patients from diagnosis included 145 adults (> 18 years). All TM patients were of Italian ethnic origin. Eleven out of 145 patients (7.5 %) developed MEC. Twenty-four other patients (12 females and 12 males) had a normal endocrine function (16.5 %) and served as controls. Results In our survey, four important, relevant aspects emerged in the MEC group. These included the late age at the start of chelation therapy with desferrioxamine mesylate (DFO); the higher serum ferritin peak (8521.8 ± 5958.9 vs 3575.2 ± 1801.4 ng/ml); the upper proportion of splenectomized (81.8 % vs. 28.5%) patients and poor compliance registered mainly during the peripubertal and pubertal age (72.7 % vs.16.6 %) in TM patients developing MEC versus those without endocrine complications. Furthermore, a negative correlation was observed in all TM patients between LIC and final height (r: −0.424; p = 0.031). Conclusions Our study supports the view that simultaneous involvement of more than one endocrine gland is not uncommon (7.5 %). It mainly occurred in TM patients who started chelation therapy with DFO late in life and who had irregular/poor compliance to treatment. Therefore

  5. Intercomparison of Operational Ocean Forecasting Systems in the framework of GODAE

    NASA Astrophysics Data System (ADS)

    Hernandez, F.

    2009-04-01

    representation, either due to model and forcing fields errors, or assimilation scheme efficiency. Comparisons to sea-ice satellite products also evidence discrepancies linked to model, forcing and assimilation strategies of each forecasting system. Key words: Intercomparison, ocean analysis, operational oceanography, system assessment, metrics, validation GODAE Intercomparison Team: L. Bertino (NERSC/Norway), G. Brassington (BMRC/Australia), E. Chassignet (FSU/USA), J. Cummings (NRL/USA), F. Davidson (DFO/Canda), M. Drévillon (CERFACS/France), P. Hacker (IPRC/USA), M. Kamachi (MRI/Japan), J.-M. Lellouche (CERFACS/France), K. A. Lisæter (NERSC/Norway), R. Mahdon (UKMO/UK), M. Martin (UKMO/UK), A. Ratsimandresy (DFO/Canada), and C. Regnier (Mercator Ocean/France)

  6. Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

    PubMed Central

    Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li

    2015-01-01

    Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson’s trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress

  7. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes.

    PubMed

    Ruggiero, Alessandro; Villa, Carlos H; Holland, Jason P; Sprinkle, Shanna R; May, Chad; Lewis, Jason S; Scheinberg, David A; McDevitt, Michael R

    2010-10-05

    Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibodyalone constructs. We performed targeted radioimmunotherapy with a SWCNT-([(225)Ac]DOTA) (E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([(89)Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that

  8. Contribution of mitochondria and lysosomes to photodynamic therapy-induced death in cancer cells

    NASA Astrophysics Data System (ADS)

    Nieminen, Anna-Liisa; Azizuddin, Kashif; Zhang, Ping; Kenney, Malcolm E.; Pediaditakis, Peter; Lemasters, John J.; Oleinick, Nancy L.

    2008-02-01

    In photodynamic therapy (PDT), visible light activates a photosensitizing drug added to a tissue, resulting in singlet oxygen formation and cell death. Employing confocal microscopy, we previously found that the phthalocyanine Pc 4 localized primarily to mitochondrial membranes in various cancer cell lines, resulting in mitochondrial reactive oxygen species (ROS) production, followed by inner membrane permeabilization (mitochondrial permeability transition) with mitochondrial depolarization and swelling, which in turn led to cytochrome c release and apoptotic death. Recently, derivatives of Pc 4 with OH groups added to one of the axial ligands were synthesized. These derivatives appeared to be taken up more avidly by cells and caused more cytotoxicity than the parent compound Pc 4. Using organelle-specific fluorophores, we found that one of these derivatives, Pc 181, accumulated into lysosomes and that PDT with Pc 181 caused rapid disintegration of lysosomes. We hypothesized that chelatable iron released from lysosomes during PDT contributes to mitochondrial damage and subsequent cell death. We monitored cytosolic Fe2+ concentrations after PDT with calcein. Fe2+ binds to calcein causing quenching of calcein fluorescence. After bafilomycin, an inhibitor of the vacuolar proton-translocating ATPase, calcein fluorescence became quenched, an effect prevented by starch desferal s-DFO, an iron chelator that enters cells by endocytosis. After Pc 181-PDT, cytosolic calcein fluorescence also decreased, indicating increased chelatable Fe2+ in the cytosol, and apoptosis occurred. s-DFO decreased Pc 181-PDT-induced apoptosis as measured by a decrease of caspase-3 activation. In isolated mitochondria preparations, Fe2+ induced mitochondrial swelling, which was prevented by Ru360, an inhibitor of the mitochondrial Ca2+ uniporter. The data support a hypothesis of oxidative injury in which Pc 181-PDT disintegrates lysosomes and releases constituents that synergistically promote

  9. Understanding public perceptions of benefits and risks of childhood vaccinations in the United States.

    PubMed

    Song, Geoboo

    2014-03-01

    In the face of a growing public health concern accompanying the reemerging threat of preventable diseases, this research seeks mainly to explain variations in the perceived benefits and risks of vaccinations among the general public in the United States. As Mary Douglas and Aaron Wildavsky's grid-group cultural theory of risk perception claims, the analytical results based upon original data from a nationwide Internet survey of 1,213 American adults conducted in 2010 suggest that individuals' cultural predispositions contribute to the formation of their perceptions pertaining to vaccine benefits and risks at both societal and individual levels, in conjunction with other factors suggested by previous risk perception literature, such as perceived prevalence of diseases, trust, knowledge level, and demographic characteristics. Those with a strong hierarch orientation tend to envision greater benefits and lesser risks and conceive of a relatively high ratio of benefit to risk when compared to other cultural types. By contrast, those with a strong fatalist tendency are inclined to emphasize risks and downplay benefits while conceiving of a low vaccination benefit-risk ratio. Situated between hierarchs and fatalists, strong egalitarians are prone to perceive greater benefits, smaller risks, and a more positive benefit-risk ratio than strong individualists.

  10. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

    PubMed Central

    Delagrange, Philippe; Krause, Diana N.; Sugden, David; Cardinali, Daniel P.; Olcese, James

    2010-01-01

    The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT1 and MT2, that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer. PMID:20605968

  11. Women's sense of coherence related to their infant feeding experiences.

    PubMed

    Thomson, Gill; Dykes, Fiona

    2011-04-01

    Given the overwhelming evidence for the benefits of breastfeeding, and yet the low prevalence rates in the UK, it is crucial to understand the influences on women's infant feeding experiences to target and promote effective support. As part of an evaluation study of the implementation of the UNICEF UK Baby Friendly Initiative (BFI) Community Award within two primary (community-based) care trusts in North West England, 15 women took part in an in-depth interview to explore their experiences, opinions and perceptions of infant feeding. In this paper, we have provided a theoretical interpretation of these women's experiences by drawing upon Aaron Antonovsky's Sense of Coherence (SOC) theory. The SOC is a global orientation to how people are able to cope with stressors and maintain a sense of well-being. The three constructs that underpin the SOC are 'comprehensibility' (one must believe that one understands the life challenge), 'manageability' (one has sufficient resources at one's disposal) and 'meaningfulness' (one must want to cope with the life challenge). In this paper, our interpretations explore how infant feeding is influenced by the 'comprehensibility', 'manageability' and 'meaningfulness' of this event; contextualized within a wider socio-cultural perspective. The findings of this paper offer a unique means through which the influences on women's experiences of infant feeding may be considered. Recommendations and suggestions for practice in relation to the implementation of the BFI have also been presented.

  12. [Salutogenic model analysis in Spain: application in public health and implications for asset health model].

    PubMed

    Rivera de los Santos, Francisco; Ramos Valverde, Pilar; Moreno Rodríguez, Carmen; Hernán García, Mariano

    2011-01-01

    This article seeks to provide an in depth review about one of the most revolutionary and influential methods used in understanding the variables and processes that explain human health. Based on a new vision in the analysis of the consequences of the Nazi Holocaust, a doctor-sociologist--Aaron Antonovsky--managed to influence medicine and behavioral science by facilitating the keys for the optimal development of public health today. Despite the fact that this theory began appearing in the 1970s in the 20th century, its real development and expansion have been seen in recent years. In fact, in Spain, there is little scientific literature that analyses the theoretic keys of the model in depth. This work seek to cover this gap; to achieve this objective, it first presents how the construct of salutogenesis arose, the social-cultural context that promoted it, as well as the importance public health acquires today. This is the aim of this work, which analyses the theoretical bases of the salutogenesis model, with specific emphasis on its background and precursors, as well as its inception, development and current expansion.

  13. Ubiquitin: molecular modeling and simulations.

    PubMed

    Ganoth, Assaf; Tsfadia, Yossi; Wiener, Reuven

    2013-11-01

    The synthesis and destruction of proteins are imperative for maintaining their cellular homeostasis. In the 1970s, Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered that certain proteins are tagged by ubiquitin before degradation, a discovery that awarded them the 2004 Nobel Prize in Chemistry. Compelling data gathered during the last several decades show that ubiquitin plays a vital role not only in protein degradation but also in many cellular functions including DNA repair processes, cell cycle regulation, cell growth, immune system functionality, hormone-mediated signaling in plants, vesicular trafficking pathways, regulation of histone modification and viral budding. Due to the involvement of ubiquitin in such a large number of diverse cellular processes, flaws and impairments in the ubiquitin system were found to be linked to cancer, neurodegenerative diseases, genetic disorders, and immunological disorders. Hence, deciphering the dynamics and complexity of the ubiquitin system is of significant importance. In addition to experimental techniques, computational methodologies have been gaining increasing influence in protein research and are used to uncover the structure, stability, folding, mechanism of action and interactions of proteins. Notably, molecular modeling and molecular dynamics simulations have become powerful tools that bridge the gap between structure and function while providing dynamic insights and illustrating essential mechanistic characteristics. In this study, we present an overview of molecular modeling and simulations of ubiquitin and the ubiquitin system, evaluate the status of the field, and offer our perspective on future progress in this area of research.

  14. Van der Waals interactions in density functional theory

    NASA Astrophysics Data System (ADS)

    Langreth, David C.

    2009-03-01

    The van der Waals density functional which we introduced half a decade agoootnotetextM. Dion et al. Phys. Rev. Lett. 92, 246401 (2004). and its self-consistent generalizationootnotetextT. Thonhauser et al., Phys. Rev. B 76, 125112 (2007). will be briefly reviewed. There are many collaborators in the application review that will follow, not only those who worked in the physics department at Rutgers% ootnotetextMaxime Dion, Aaron Puzder, T. Thonhauser, Valentino R. Cooper, Shen Li, Eamonn Murray, Lingzhu Kong, and Kyuho Lee. and at Chalmers,% ootnotetextHenrik Rydberg, Svetla Chakarova-K"ack, Jesper Kleis, Elsebeth Schr"oder, Per Hyldgaard, and Bengt I. Lundqvist. but also at Denmarks Technical University,% ootnotetextAndrei Kelkkanen, Poul G. Moses, Jesper Kleis, and Bengt I. Lundqvist. the chemistry department at Rutgers,% ootnotetextKonhoa Li, Jing Li, Yves Chabal, and Wilma K. Olson. and most recently at the University of Texas at Dallas.% ootnotetextNour Nijem and Yves Chabal. I will expand on our recent review article,ootnotetextD. C. Langreth et al., J. Phys. Cond. Mat. (in press). which hopefully will be published before the present talk, and include applications by other groups not listed below. If possible, I will also review results from a more recent collaboration to study nucleosomal DNA and beyond.

  15. [The Jung model of active style of schema].

    PubMed

    Ogłodek, Ewa; Araszkiewicz, Aleksander

    2011-12-01

    Yung was of an opinion that the borderline personality as a pathology results from the experiences of a frightened and violence-experiencing child who is left to their own devices in the hostile world. In that situation, the child, longing for safety, simultaneously experiences fear of abuse, hurt and rejection and remains distrustful. In order to understand the dramatic changes in the individual's behaviour, in case of the borderline personality disorders, Yung developed the concept, presented by Aaron Beck at the therapeutic workshops in the 1980s. Beck's concept was based upon the assumption that some pathological states expressed strong emotional states, experienced in childhood on the basis of regression. Yung presented them in the form of conceptualization in the categories of the active styles of schema. Apart from the states of regression, he also differentiated less regressive styles of schema. The style of schema should be interpreted as a pattern of experiencing, thinking and behaviour, based upon a determined set of schema, and characterized by independence from other styles.

  16. Sense of coherence and physical health. The emotional sense of coherence (SOC-E) was found to be the best-known predictor of physical health.

    PubMed

    Flensborg-Madsen, Trine; Ventegodt, Søren; Merrick, Joav

    2006-06-22

    In this study, we created a measure for emotionality named the emotional sense of coherence (SOC-E). We found that SOC-E was significantly associated with physical health (r = 0.266; p < 0.05), while it was not significantly associated with psychological health (r = 0.006; NS). Based on a correlation matrix, we constructed a new scale, the SOC-E II, which was even better associated with physical health (r = 0.362) and also associated with psychological health (r = 0.259; p < 0.01). Our results showed that SOC-E and SOC-E II were better predictors of physical health than the SOC scales developed by Aaron Antonovsky (1923-1994) (SOC-29 and SOC-13). We conclude that emotional coherence is important for physical health, but it is not important in the same way for psychological health. In a previous study, we found that a mental operationalization of Antonovsky's sense of coherence was highly associated with psychological health and not associated with physical health. Based on these two studies, we conclude that physical health is primarily associated with emotions, while psychological health is primarily associated with mentality.

  17. Sense of coherence and physical health. A "Copenhagen interpretation" of Antonovsky's SOC concept.

    PubMed

    Endler, P Christian; Haug, Thomas M; Spranger, Heinz

    2008-04-20

    According to Antonovsky's (Aaron Antonovsky, 1923-1994) sense of coherence (SOC) model, persons with a high SOC have the ability to benefit from their general defense mechanisms in order to overcome stressful situations. In a health-disease continuum, this leads to the development towards health. However, Antonovsky's global hypothesis that the strength of the SOC may influence the physical health status of a person could not be proven. Flensborg-Madsen et al. from Copenhagen were able to provide a new access regarding SOC and health. They investigated the mixture of emotional aspects and mental constructions as a possible cause for fairly low correlation between SOC and physical health. Thus, in an empirical way, they described "emotional coherence" in relation to physical health, while "mental coherence" was linked to psychological health. These authors introduced the idea of applying a shortened version of the original 29-item SOC questionnaire, but have not yet developed or tested the shortened questionnaire. Backed by their important findings, it appears to be promising to consider the use of the SOC questionnaire as standardized by Antonovsky, but cleared of the items regarding "predictability", i.e., Flensborg-Madsen et al. suggested that the items on "predictability" be excluded from the SOC scale when a correlation to physical health is to be investigated. Further investigations in this area of research will be of high impact, not only for health sciences, but also for medical practice.

  18. Sense of coherence and physical health. A cross-sectional study using a new scale (SOC II).

    PubMed

    Flensborg-Madsen, Trine; Ventegodt, Søren; Merrick, Joav

    2006-10-09

    In this study, we constructed a new sense of coherence scale (SOC II), where we eliminated the notion of predictability (that life is meant to be predictable), which was present in the original SOC scale developed by Aaron Antonovsky (1923-1994) (SOC-29 and SOC-13). Our hypothesis was that SOC II would show a higher degree of association with physical health than the original SOC scale. In order to test this idea, we used a cross-sectional study including 4,648 Danes and used the three different health measures: self-evaluated physical health, physical symptoms, and self-evaluated psychological health. We found that SOC II was positively associated with all three health measures with the correlation coefficients 0.338, 0.282, and 0.578, respectively. Furthermore, we found dose response tendencies for all three health measures across groups of SOC, since health improved with a higher SOC. By means of regression analysis, we found that SOC was significantly associated with all three health measures after stratifying for demographic variables, life style variables, life form variables, and attitude variables, respectively. We conclude from this study that the SOC II scale we developed seems better associated with physical health than found with the original SOC scale. We also postulate that the concept of predictability was irrelevant, or even disturbing, and should not be included in the SOC scale.

  19. Sense of coherence (SOC) among psychotherapists in Austria, differentiated according to number of individually completed training therapy sessions.

    PubMed

    Binder, Heinz P; Mesenholl-Strehler, Elke; Pass, Paul; Endler, P Christian

    2006-10-02

    The sense of coherence (according Aaron Antonovsky, 1923-1994, when a person's sense that his/her own life and the world are sufficiently comprehensible, manageable, and meaningful) of Austrian psychotherapists was assessed and compared with a standard sample, as well as with the sense of coherence (SOC) of members of other professions. In addition, the question as to whether psychotherapists who had completed more extensive individual training therapy/self-awareness sessions had a higher SOC than do those with fewer, was addressed. Forty psychotherapists who worked in private practices and various psychosocial health care institutions in Styria, Austria took part in the study. The investigation was conducted in the form of a questionnaire assessment. The evaluation showed that the overall SOC value of the professional group in question was significantly higher than that of the standard sample (162.3 vs. 145.7), as well as other samples (physicians: SOC = 153.8; teachers: SOC = 156.1; physiotherapists SOC = 158.1). Concerning whether psychotherapists who had completed more individual training therapy/self-awareness sessions had higher SOC values than did those with fewer, we found no difference in regard to the overall SOC score or SOC scores for individual components. The SOC of psychotherapists did not seem to depend on the number of additional training therapy/self-awareness sessions.

  20. [The Bilbao declaration: international meeting on the law concerning the human genome project].

    PubMed

    1994-06-01

    The Bilbao statement was the result of a work meeting, held the day before the closing session by a group of representative experts, formed by general chairmen and meeting organizers. The compelled and necessary consent gave rise to the document that was read and communicated to the world's public opinion during the closing act on may 26, 1993. Notwithstanding, the working group considered that the divulged version was provisory and committed to continue the task of re-elaborating the statement. The aim was to complete and improve it, taking the greatest advantage of the important meeting achievements. The document that is next reproduced is the definitive integral version of the Bilbao Statement. The expert group that takes the responsibility of this Statement is Jean Dausset, Nobel Prize of Medicine (1980); Carleton Gajdusek, Nobel Prize of Medicine (1976); Santiago Grisolía president of UNESCO committee for the Genome Project; Michael Kirby, President of the Court of Appeal of the Supreme Court of New South Wales, Australia; Aaron Klug, member of the Constitutional Council, Paris, France; Rafael Mendizábal, Judge of the Constitutional Court, Madrid, Spain; Juan Bautista Pardo, President of the Superior Court of Justice of the Basque Country and Carlos María Romeo Casabona, Director of the Chair of Law and Human Genome of the University of Deusto (Bilbao).