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Sample records for aaron yeow dfo

  1. What Aaron Taught Me about Fluency

    ERIC Educational Resources Information Center

    Brand, Max

    2006-01-01

    In this article, the author shares the lessons he learned from Aaron, a 12-year old kid who had never been to school, on the importance of crafting systematic fluency lessons. The following are strategies that worked for them: (1) Demonstrate what fluency sounds and feels like; (2) Read aloud to the students at least three times a day from a…

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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).

  7. 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

  8. 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.

  9. 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

    ... the Federal Register on January 25, 2010 (75 FR 3932). Pursuant to 29 CFR 90.18(c) reconsideration may... warehousing services of jewelry during the relevant period. Samuel Aaron, Inc., did not import these...

  10. 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

  11. Culture in salutogenesis: the scholarship of Aaron Antonovsky.

    PubMed

    Benz, Carina; Bull, Torill; Mittelmark, Maurice; Vaandrager, Lenneke

    2014-12-01

    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. 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…

  13. 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…

  14. Aaron Douglas and Hale Woodruff: African American Art Education, Gallery Work, and Expanded Pedagogy

    ERIC Educational Resources Information Center

    Bey, Sharif

    2011-01-01

    This analysis of archival materials discovered at Fisk and Atlanta Universities examines the teaching careers of Aaron Douglas and Hale Woodruff, two African American artists who came to prominence during the New Negro Movement in the 1920s and taught at historically Black universities in the 1930s and 1940s. These artists had a profound influence…

  15. You Gotta Have a Gimmick: Aaron Coutu--Greenville Public Library, RI

    ERIC Educational Resources Information Center

    Library Journal, 2004

    2004-01-01

    This brief article describes the impact Aaron Coutu has had on the teens at the Greenville Public Library in Rhode Island. Coutu has gotten on the good side of many of the teens in the library since he is willing to undergo various personal humiliations, like shaving his head if they read 150 books (they read 196) or dyeing his hair green if they…

  16. 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…

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. The superoxide dismutase (SOD)-mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock

    SciTech Connect

    de Garavilla, L.; Chermak, T.; Valentine, H.L.; Hanson, R.C. )

    1990-02-26

    The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by complete autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.

  3. Aluminum-related osteomalacia: clinical and histological improvement following treatment with desferrioxamine (DFO).

    PubMed

    Rapoport, J; Chaimovitz, C; Abulfil, A; Mostovlavsky, M; Gazit, D; Bab, I

    1987-12-01

    Aluminum-related osteomalacia has been a topic of major interest for some time. Patients on dialysis who are affected exhibit reduced parathyroid function and osteomalacia associated with high levels of aluminum in the extracellular fluid and tissues. In bone, aluminum is found in the interface between mineralized and nonmineralized osteoid. In the present study we attempted treatment of the aluminum-related bone disease with DFO, a potent chelating agent. A thyroparathyroidectomized patient on hemodialysis with proven osteomalacia and aluminum deposits in bone received DFO 3 times/week for 1 year. Consequently, there was a marked improvement in his skeletal status, both clinically and histologically. This was associated with aluminum deposits within the mineralized component of bone as well as elevated parathyroid function measured in blood and bone. These findings suggest that calcification may occur despite the presence of aluminum in the mineralizing front. The main beneficial effect of DFO could be relief of the inhibitory action of aluminum on parathyroid cells and osteoblasts. PMID:3440748

  4. 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.

  5. Effect of desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) on rat cytomegalovirus replication in vitro and in vivo.

    PubMed

    Kloover, J S; Scholz, M; Cinatl, J; Lautenschlager, I; Grauls, G E; Bruggeman, C A

    1999-11-01

    Cytomegalovirus (CMV) infection is a major problem in the immunosuppressed patient. It is thought that besides direct CMV induced cell lysis, immunological damage is part of CMV pathogenesis. New antiviral drugs, which combine immunomodulating and antiviral qualities, could be beneficial. Recently, it has been described that desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) exhibit both properties. In this report the antiviral effects of both compounds against rat CMV (RCMV) are described in vitro and in vivo using a generalised and local infection model. In vitro, both compounds exhibited a significant antiviral effect, DTPA being more potent than DFO. However, in the generalised infection model no effect was seen on mortality, morbidity or presence of virus in internal organs. In rats infected subcutaneously in the hind paw, no effect was seen locally on paw thickness, presence of viral antigens and inflammatory response. In addition, these rats suffered from a generalised infection of low magnitude at 15 days post infection, although both DFO and DTPA were able to lower the level of viral replication. In conclusion, our data indicate that despite in vitro activity, in vivo usage of DFO or DTPA for acute CMV infection is not warranted.

  6. Effect of microbial siderophore DFO-B on Cd accumulation by Thlaspi caerulescens hyperaccumulator in the presence of zeolite.

    PubMed

    Karimzadeh, Lotfollah; Heilmeier, Hermann; Merkel, Broder J

    2012-07-01

    Hyperaccumulators are grown in contaminated soil and water in order that contaminants are taken up and accumulated. Transport of metals from soil to plant is initially dependent on the solubility and mobility of metals in soil solution which is controlled by soil and metal properties and plant physiology. Complexation with organic and inorganic ligands may increase mobility and availability of metals for plants. In this work the influence of desferrioxamine-B (DFO-B), which naturally is produced in the rhizosphere, and zeolite on Cd accumulation in root and shoot of Thlaspi caerulescens (Cd hyperaccumulator) was investigated. Plants were grown in pots with clean quartz sand, amended with 1% zeolite; treatment solutions included 0, 10, and 100 μM Cd and 70 μM DFO-B. Addition of zeolite to the quartz sand significantly reduced Cd concentration in plant tissues and translocation from root to shoot. On contrary, DFO-B considerably enhanced Cd sorption by roots and translocation to aerial part of plants. Treating the plants with zeolite and DFO-B together at 10 μM Cd resulted in reduction of the bioaccumulation factor but enhancement of Cd translocation from root to shoot at the rate of 13%. In contrast, at 100 μM Cd in the solution both bioaccumulation and translocation factors decreased. Total metal accumulation as a key factor for evaluating the efficiency of phytoremediation was highly influenced by treatments. Presence of zeolite in pots significantly decreased total Cd accumulation by plants, whereas, DFO-B clearly enhanced it. PMID:22572166

  7. 89Zr-DFO-J591 for immunoPET imaging of prostate-specific membrane antigen (PSMA) expression in vivo

    PubMed Central

    Holland, Jason P.; Divilov, Vadim; Bander, Neil H.; Smith-Jones, Peter M.; Larson, Steven M.; Lewis, Jason S.

    2010-01-01

    Zirconium-89 (t1/2 = 3.27 days) is a positron emitting radionuclide which displays excellent potential for use in the design and synthesis of radioimmunoconjugates for immunoPET. In these studies we report the preparation of 89Zr-DFO-J591, a novel 89Zr -labeled monoclonal antibody (mAb) construct for targeted immunoPET imaging and quantification of prostate-specific membrane antigen (PSMA) expression in vivo. Methods The in vivo behavior of [89Zr]Zr-chloride, [89Zr]Zr-oxalate and [89Zr]Zr-DFO was investigated by using PET imaging. High level computational studies using density functional theory (DFT) calculations have been used to investigate the electronic structure of [89Zr]Zr-DFO and probe the nature of the complex in aqueous conditions. J591 was functionalized with the hexadentate, tris-hydroxamate ligand desferrioxamine B (DFO) and radiolabeled with [89Zr]Zr-oxalate at room temperature. ImmunoPET imaging experiments in male, athymic nu/nu mice bearing sub-cutaneous LNCaP (PSMA positive) or PC-3 (PSMA negative) tumors were conducted. The change in 89Zr-DFO-J591 tissue uptake in response to high- and low-specific-activity formulations in the two tumor models was measured by using acute biodistribution studies and immunoPET. Results Basic characterization of three important reagents, [89Zr]Zr-chloride and [89Zr]Zr-oxalate, as well as the complex, [89Zr]Zr-DFO, demonstrated that the nature of the 89Zr species has a dramatic effect on the biodistribution and pharmacokinetics. DFT calculations provide a rationale for the observed high in vivo stability of 89Zr-DFO-labeled mAbs and suggest that in aqueous conditions, [89Zr]Zr-DFO forms a thermodynamically stable, 8-coordinate complex by coordination of two water molecules. 89Zr-DFO-J591 was produced in high radiochemical yield (>77%) with radiochemical purity >99% and a specific-activity of 181.7±1.1 MBq/mg (4.91±0.03 mCi/mg). In vitro assays demonstrated that 89Zr-DFO-J591 had an initial immunoreactive fraction of

  8. ["The future must look to the past"* : Prof. Dr. Abraham Aaron Buschke (1868-1943) and Wilhelm Ludwig Löwenstein (1895-1959)].

    PubMed

    Dräger, D L; Protzel, C; Hakenberg, O W

    2015-11-01

    Like many other areas of medicine, dermatology with its comparatively high proportion of Jewish physicians was also not spared from the National Socialist appointment policy with dismissals, laws on "appreciation of the people", research influenced by National Socialist policies, and persecution of Jewish physicians. Prof. Abraham Aaron Buschke and Dr. Wilhelm Ludwig Lowenstein, who were the first to describe the Buschke-Lowenstein tumor, also suffered this destiny. In March 1933, Professor Buschke was dismissed from the position of directing physician at the Virchow Hospital in Berlin and in 1934 his teaching license was revoked. Despite affidavits of his "loyalty to the regime", Dr. Lowenstein fared the same treatment.

  9. ["The future must look to the past"* : Prof. Dr. Abraham Aaron Buschke (1868-1943) and Wilhelm Ludwig Löwenstein (1895-1959)].

    PubMed

    Dräger, D L; Protzel, C; Hakenberg, O W

    2015-11-01

    Like many other areas of medicine, dermatology with its comparatively high proportion of Jewish physicians was also not spared from the National Socialist appointment policy with dismissals, laws on "appreciation of the people", research influenced by National Socialist policies, and persecution of Jewish physicians. Prof. Abraham Aaron Buschke and Dr. Wilhelm Ludwig Lowenstein, who were the first to describe the Buschke-Lowenstein tumor, also suffered this destiny. In March 1933, Professor Buschke was dismissed from the position of directing physician at the Virchow Hospital in Berlin and in 1934 his teaching license was revoked. Despite affidavits of his "loyalty to the regime", Dr. Lowenstein fared the same treatment. PMID:26450094

  10. '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. PMID:25114145

  11. '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.

  12. ‘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

  13. Measuring the Pharmacodynamic Effects of a Novel Hsp90 Inhibitor on HER2/neu Expression in Mice Using 89Zr-DFO-Trastuzumab

    PubMed Central

    Holland, Jason P.; Caldas-Lopes, Eloisi; Divilov, Vadim; Longo, Valerie A.; Taldone, Tony; Zatorska, Danuta; Chiosis, Gabriela; Lewis, Jason S.

    2010-01-01

    Background The positron-emitting radionuclide 89Zr (t1/2 = 3.17 days) was used to prepare 89Zr-radiolabeled trastuzumab for use as a radiotracer for characterizing HER2/neu-positive breast tumors. In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted. Methodology/Principal Findings Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with [89Zr]Zr-oxalate at room temperature using modified literature methods. ImmunoPET and biodistribution experiments in female, athymic nu/nu mice bearing sub-cutaneous BT-474 (HER2/neu positive) and/or MDA-MB-468 (HER2/neu negative) tumor xenografts were conducted. The change in 89Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. 89Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.3±2.1 MBq/mg (2.82±0.05 mCi/mg of mAb). In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87±0.07. In vivo biodistribution experiments revealed high specific BT-474 uptake after 24, 48 and 72 h (64.68±13.06%ID/g; 71.71±10.35%ID/g and 85.18±11.10%ID/g, respectively) with retention of activity for over 120 h. Pre-treatment with PU-H71 was followed by biodistribution studies and immunoPET of 89Zr-DFO-trastuzumab. Expression levels of HER2/neu were modulated during the first 24 and 48 h post-administration (29.75±4.43%ID/g and 41.42±3.64%ID/g, respectively). By 72 h radiotracer uptake (73.64±12.17%ID/g) and Western blot analysis demonstrated that HER2/neu expression recovered to baseline levels. Conclusions/Significance The results indicate that 89Zr-DFO-trastuzumab provides quantitative and highly-specific delineation of HER2/neu positive tumors, and has

  14. 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:

  15. 77 FR 51752 - Medbow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie, Wyoming 82070. Comments may also be sent via email to..., 2468 Jackson Street, Laramie, Wyoming. Please call ahead to 307-745- 2300 to facilitate entry into the building to view comments. FOR FURTHER INFORMATION CONTACT: Aaron Voos, RAC Coordinator, 2468...

  16. 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…

  17. 75 FR 32740 - Action Affecting Export Privileges; Aaron Robert Henderson and Valhalla Tactical Supply

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... 1950 (50 U.S.C. 783(b)), or section 38 of the Arms Export Control Act (22 U.S.C. 2778).'' 15 CFR 766.25... (74 FR 41325, August 14, 2009)), has continued the Regulations in effect under the International... ordering, buying, receiving, using, selling, delivering, storing, disposing of, forwarding,...

  18. 76 FR 66969 - Aaron Gloskowski, D.O.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    .... David W. Wang, 72 FR 54297, 54298 (2007); Sheran Arden Yeates, 71 FR 39130, 39131 (2006); Dominick A. Ricci, 58 FR 51104, 51105 (1993); Bobby Watts, 53 FR 11919, 11920 (1988). See also 21 U.S.C. 824(a)(3... considered in the disjunctive. Robert A. Leslie, 68 FR 15227, 15230 (2003). I may rely on any one or...

  19. In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator.

    PubMed

    Hamilton, Jasmine L; Imran Ul-Haq, Muhammad; Abbina, Srinivas; Kalathottukaren, Manu Thomas; Lai, Benjamin F L; Hatef, Azadeh; Unniappan, Suraj; Kizhakkedathu, Jayachandran N

    2016-09-01

    Desferrioxamine (DFO) is currently in clinical use to remove iron from transfusion-dependent patients with β-thalassemia major, sickle-cell anemia and the myelodysplastic syndromes. However, its short half-life, burdensome, subcutaneous mode of administration and propensity to cause neurotoxicity at high doses greatly hinder its use. Thus, developing an optimized version of DFO with extended half-life, and reduced toxicity is a major goal. Using high molecular weight (MW), non-toxic, hyperbranched polyglycerol with high functionality, we demonstrate that the efficacy of DFO can be tuned with considerable reduction in toxicity. Using zebrafish embryos and mice, we tested toxicity, iron removal efficacy with low dosing and the biodistribution of ultra-long circulating DFO (ULC-DFO) conjugates. There was no significant difference in the mortality and development of zebrafish embryos upon exposure to ULC-DFO. Similarly, body weights and serum lactate dehydrogenase levels in mice treated with ULC-DFO remained within the normal range throughout the tolerance study. Moreover, ULC-DFO is significantly more effective than low MW DFO in promoting iron removal both from organs and via urine in iron overloaded mice despite using a moderate, once-weekly dosing schedule. This is probably due to the extended circulation half-life of ULC-DFO. The MW of ULC-DFO influences the accumulation and biodistribution, with highest MW (637 KDa) associated with up to 12% accumulation in the liver. In contrast, ULC-DFO with MWs of 75 KDa and lower were associated with relatively low organ accumulation, indicating that biodistribution of ULC-DFO can be tuned. Since ULC-DFO has improved iron removal properties, longer plasma retention time and possesses excellent biocompatibility, it represents a polymer conjugate with high clinical utility in comparison to DFO for the treatment of transfusion dependent iron overload. More importantly, ULC-DFO is anticipated to reduce the requirement for

  20. 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.

  1. Desferrioxamine Inhibits Protein Tyrosine Nitration: Mechanisms and Implications

    PubMed Central

    Adgent, Margaret A.; Squadrito, Giuseppe L.; Ballinger, Carol A.; Krzywanski, David M.; Lancaster, Jack R.; Postlethwait, Edward M.

    2012-01-01

    Tissues are exposed to exogenous and endogenous nitrogen dioxide (•NO2), which is the terminal agent in protein tyrosine nitration. Besides iron chelation, the hydroxamic acid (HA) desferrioxamine (DFO) shows multiple functionalities including nitration inhibition. To investigate mechanisms whereby DFO affects 3-nitrotyrosine (3-NT) formation, we utilized gas phase •NO2 exposures, to limit introduction of other reactive species, and a lung surface model wherein red cell membranes (RCM) were immobilized under a defined aqueous film. When RCM were exposed to •NO2 covered by +/− DFO: (i) DFO inhibited 3-NT formation more effectively than other HA and non-HA chelators; (ii) 3-NT inhibition occurred at very low [DFO] for prolonged times; and (iii) 3-NT formation was iron independent but inhibition required DFO present. DFO poorly reacted with •NO2 compared to ascorbate, assessed via •NO2 reactive absorption and aqueous phase oxidation rates, yet limited 3-NT formation at far lower concentrations. DFO also inhibited nitration under aqueous bulk phase conditions, and inhibited 3-NT generated by active myeloperoxidase “bound” to RCM. Per the above and kinetic analyses suggesting preferential DFO versus •NO2 reaction within membranes, we conclude that DFO inhibits 3-NT formation predominantly by facile repair of the tyrosyl radical intermediate, which prevents •NO2 addition, and thus nitration, and potentially influences biochemical functionalities. PMID:22705369

  2. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23924612

  4. Two cell cycle blocks caused by iron chelation of neuroblastoma cells: separating cell cycle events associated with each block

    PubMed Central

    Siriwardana, Gamini; Seligman, Paul A.

    2013-01-01

    Abstract Studies have presented evidence that besides the well described S phase block, treatment of cancer cell lines with the iron chelator deferrioxamine (DFO) also results in an earlier block in G1 phase. In this article, measurements of cell cycle regulatory proteins define this block at a very specific point in G1. DFO treatment results in markedly decreased cyclin A protein levels. Cyclin E levels that accumulate in early to mid‐G1 are increased in cells treated with DFO as compared to the resting cells. The DFO S phase block is shown after cells are arrested at G1/S by (aphidicolin) then released into DFO. The same S phase block occurs with DFO treatment of a neuroblastoma cell line relatively resistant to the G1 DFO block. These experiments clearly differentiate the S phase DFO block from the earlier block pinpointed to a point in mid‐G1, before G1/S when cyclin E protein increases but before increased cyclin A synthesis. Apoptosis was observed in cells inhibited by DFO at both cell cycle arrest points. PMID:24744856

  5. Two cell cycle blocks caused by iron chelation of neuroblastoma cells: separating cell cycle events associated with each block.

    PubMed

    Siriwardana, Gamini; Seligman, Paul A

    2013-12-01

    Studies have presented evidence that besides the well described S phase block, treatment of cancer cell lines with the iron chelator deferrioxamine (DFO) also results in an earlier block in G1 phase. In this article, measurements of cell cycle regulatory proteins define this block at a very specific point in G1. DFO treatment results in markedly decreased cyclin A protein levels. Cyclin E levels that accumulate in early to mid-G1 are increased in cells treated with DFO as compared to the resting cells. The DFO S phase block is shown after cells are arrested at G1/S by (aphidicolin) then released into DFO. The same S phase block occurs with DFO treatment of a neuroblastoma cell line relatively resistant to the G1 DFO block. These experiments clearly differentiate the S phase DFO block from the earlier block pinpointed to a point in mid-G1, before G1/S when cyclin E protein increases but before increased cyclin A synthesis. Apoptosis was observed in cells inhibited by DFO at both cell cycle arrest points.

  6. Alterations of the [59Fe]ferric citrate biodistribution in hyperferremic mice after the administration of pyrophosphate and desferrioxamine.

    PubMed

    Sawas-Dimopoulou, C; Soulpi, C

    1983-02-01

    One of the most efficient anions in enhancing the ability of desferrioxamine (DFO) to remove iron from transferrin in vitro has been shown to be pyrophosphate (PYP). To evaluate the in vivo effect of PYP in hyperferremic mice, the biodistribution of [59Fe]ferric citrate was studied after the i.p. administration of: 1) only saline in the control animals; 2) an aqueous solution of tetrasodium diphosphate (PYP; 40 gm/2 g of b.wt.); 3) desferral (DFO; 12 mg/20 g of b.wt.); and 4) PYP + DFO at the respective dosages shown above. The radioactivity in each organ, blood, urine and feces was measured and referred to as percentage of the injected dose. PYP administered alone acted as a weaker chelator of iron than DFO. The combined administration of DFO and PYP contributed more than DFO or PYP separately, to the increase of urinary excretion of 59Fe and to the significant decrease of the radioiron concentration in liver (.01 less than P less than .05). The above induced changes are not, however, the additive result of the separate effect of DFO and PYP. That observation would suggest that DFO + PYP combined in a unique treatment, interact with iron through a common reaction pathway and that PYP plays in vivo a synergistic role in that interaction. The kind of iron with which DFO + PYP interacts is then suggested to be the transferrin-bound iron located in extracellular spaces of tissues.

  7. Alterations of the (/sup 59/Fe)ferric citrate biodistribution in hyperferremic mice after the administration of pyrophosphate and desferrioxamine

    SciTech Connect

    Sawas-Dimopoulou, C.; Soulpi, C.

    1983-02-01

    One of the most efficient anions in enhancing the ability of desferrioxamine (DFO) to remove iron from transferrin in vitro has been shown to be pyrophosphate (PYP). To evaluate the in vivo effect of PYP in hyperferremic mice, the biodistribution of (/sup 59/Fe)ferric citrate was studied after the i.p. administration of: 1) only saline in the control animals; 2) an aqueous solution of tetrasodium diphosphate (PYP; 40 gm/2 g of b.wt.); 3) desferral (DFO; 12 mg/20 g of b.wt.); and 4) PYP + DFO at the respective dosages shown above. The radioactivity in each organ, blood, urine and feces was measured and referred to as percentage of the injected dose. PYP administered alone acted as a weaker chelator of iron than DFO. The combined administration of DFO and PYP contributed more than DFO or PYP separately, to the increase of urinary excretion of /sup 59/Fe and to the significant decrease of the radioiron concentration in liver (.01 less than P less than .05). The above induced changes are not, however, the additive result of the separate effect of DFO and PYP. That observation would suggest that DFO + PYP combined in a unique treatment, interact with iron through a common reaction pathway and that PYP plays in vivo a synergistic role in that interaction. The kind of iron with which DFO + PYP interacts is then suggested to be the transferrin-bound iron located in extracellular spaces of tissues.

  8. The mechanism of antiproliferative effect of desferrioxamine on human hepatoma cell lines.

    PubMed

    Kim, D Y; Kim, W H; Kang, J K; Park, S; Kwon, O H

    1994-03-01

    We investigated the effect of desferrioxamine (DFO), an iron chelator, on the DNA synthesis and the cell cycle of cultured hepatoma cells. Using Hep 3B cells as the hepatoma cell lines, DNA synthesis was measured by [3H] thymidine incorporation, and the cell cycle analysis was performed by flow cytometry including bivariate DNA/BrdU analysis. [3H] thymidine uptake was decreased by DFO in a dose dependent manner. The proportion of S phase cells increased and that of G0/G1 phase cells decreased after the addition of DFO in the culture media in a dose dependent manner up to 20 micrograms/ml of DFO. The S phase duration of the exponentially proliferating Hep 3B cells was 9.9 hours when cultured without DFO, but it was markedly prolonged (54.1 hours) after the addition of 20 micrograms/ml of DFO. After removal of DFO from the culture media following 24 hours of incubation with 20 micrograms/ml of DFO, a sequential increase from early through mid and late-S to G2/M phase was observed. In conclusion, the antiproliferative effect of DFO on cultured human hepatoma cell lines was caused by the inhibition of DNA synthesis which was related to a block in the early-mid S interface or mid S phase of the cell cycle. PMID:8009898

  9. 76 FR 11494 - List of Recipients of Indian Health Scholarships Under the Indian Health Scholarship Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ..., Southwestern Oklahoma State University, Choctaw Nation of Oklahoma Debolt, Nicholas D., University of Oklahoma...., Southwestern Community College, Eastern Band of Cherokee Indians of North Carolina Sparks, Aaron D.,...

  10. 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.

  11. 77 FR 68746 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... will improve organizational effectiveness by providing comprehensive content management and enterprise... (February 20, 1996, 61 FR 6427). Dated: November 13, 2012. Aaron Siegel, Alternate OSD Federal...

  12. Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells.

    PubMed

    Link, Gabriela; Ponka, Prem; Konijn, Abraham M; Breuer, William; Cabantchik, Z Ioav; Hershko, Chaim

    2003-05-15

    Although iron chelation therapy with deferoxamine (DFO) results in improved life expectancy of patients with thalassemia, compliance with parenteral DFO treatment is unsatisfactory, underlining the need for alternative drugs and innovative ways of drug administration. We examined the chelating potential of pyridoxal isonicotinoyl hydrazone (PIH) analogs, alone or in combination with DFO, using hypertransfused rats with labeled hepatocellular iron stores and cultured iron-loaded rat heart cells. Our in vivo studies using 2 representative PIH analogs, 108-o and 109-o, have shown that PIH analogs given orally are 2.6 to 2.8 times more effective in mobilizing hepatocellular iron in rats, on a weight-per-weight basis, than parenteral DFO administered intraperitoneally. The combined effect of DFO and 108-o on hepatocellular iron excretion was additive, and response at a dose range of 25 to 200 mg/kg was linear. In vitro studies in heart cells showed that DFO was more effective in heart cell iron mobilization than all PIH analogs studied. Response to joint chelation with DFO and PIH analogs was similar to an increase in the equivalent molar dose of DFO alone, rather than the sum of the separate effects of the PIH analog and DFO. This finding was most likely the result of iron transfer from PIH analogs to DFO, a conclusion supported directly by iron-shuttle experiments using fluorescent DFO. These findings provide a rationale for the combined, simultaneous use of iron-chelating drugs and may have useful, practical implications for designing novel strategies of iron chelation therapy.

  13. 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.

  14. Gamma and pulse radiolysis investigation of the reaction of desferrioxamine with superoxide anions.

    PubMed

    Sabourault, D; Ribiere, C; Nordmann, R; Houee-Levin, C; Ferradini, C

    1989-12-01

    The kinetic scheme of the reaction of desferrioxamine (DFO) with O2-. was studied using pulse and gamma-radiolysis. The rate constant k(O2-. + DFO) is equal to 1.3 +/- 0.1 x 10(6) dm3 mol-1s-1 at pH 7.4. Studying the competition between DFO and ferricytochrome-c for O2-. generated by gamma-radiolysis, we observed that the nitroxide free radical resulting from the reaction of O2-. with DFO and the product(s) resulting from the decay of this nitroxide radical act inversely towards the cytochrome-c-Fe3+/cytochrome-c-Fe2+ redox couple. This explains the discrepancy between our value of k(O2-. + DFO) and the one measured previously using ferricytochrome-c for the detection of O2-. The reported results show that DFO acts as a powerful O2-. scavenger, and that the products resulting from the reaction of DFO with O2-. can initiate oxidative and/or reductive reactions that should be taken into account in interpreting the effects of DFO in vitro and in vivo. PMID:2574220

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. Alterations of the (/sup 59/Fe)ferric citrate biodistribution in hyperferremic mice after the administration of pyrophosphate and desferrioxamine

    SciTech Connect

    Sawas-Dimopoulou, C.; Soulpi, C.

    1983-02-01

    One of the most efficient anions in enhancing the ability of desferrioxamine (DFO) to remove iron from transferrin in vitro has been shown to be pyrophosphate (PYP). To evaluate the in vivo effect of PYP in hyperferremic mice, the biodistribution of (/sup 59/Fe)ferric citrate was studied after the i.p. administration of: 1) only saline in the control animals; 2) an aqueous solution of tetrasodium diphosphate; 3) desferral; and 4) PYP + DFO. The radioactivity in each organ, blood, urine and feces was measured and referred to as percentage of the injected dose. PYP administered alone acted as a weaker chelator of iron than DFO. The combined administration of DFO and PYP contributed more than DFO or PYP separately, to the increase of urinary excretion of 59Fe and to the significant decrease of the radioiron concentration in liver. The above induced changes are not, however, the additive result of the separate effect of DFO and PYP. That observation would suggest that DFO + PYP combined in a unique treatment, interact with iron through a common reaction pathway and that PYP plays in vivo a synergistic role in that interaction. The kind of iron with which DFO + PYP interacts is then suggested to be the transferrin-bound iron located in extracellular spaces of tissues.

  1. 76 FR 12211 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ...: one hard copy with original signature or one electronic copy via e-mail. An agenda will be posted on... contact Susan Lender, DFO, (the Contact Person listed below) by phone or e-mail for the teleconference... Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail) by March 14, 2011,...

  2. 76 FR 4988 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... following formats: One hard copy with original signature or one electronic copy via e-mail. An agenda will... contact Susan Lender, DFO, (the Contact Person listed below) by phone or e-mail for the teleconference... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail)...

  3. 78 FR 28619 - Boston Harbor Islands Advisory Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-15

    ...: Bruce Jacobson, DFO, Boston Harbor Islands National Recreation Area, 15 State Street, Suite 1100, Boston, MA 02109; telephone (617) 223-8669; email Bruce_Jacobson@nps.gov . SUPPLEMENTARY INFORMATION: This... Official (DFO) for the Boston Harbor Islands Advisory Council, Bruce Jacobson, by mail at State...

  4. Deferoxamine mesylate enhances virulence of community-associated methicillin resistant Staphylococcus aureus.

    PubMed

    Arifin, Andrew J; Hannauer, Mélissa; Welch, Ian; Heinrichs, David E

    2014-11-01

    Staphylococcus aureus is a leading cause of bacterial infections. Strains of community-associated methicillin-resistant S. aureus (CA-MRSA), such as USA300, display enhanced virulence and fitness. Patients suffering from iron overload diseases often undergo iron chelation therapy with deferoxamine mesylate (DFO). Here, we show that USA300 uses this drug to acquire iron. We further demonstrate that mice administered DFO I.P., versus those not administered DFO, had significantly higher bacterial burden in livers and kidneys after I.V. challenge with USA300, associated with increased abscess formation and tissue destruction. The virulence of USA300 mutants defective for DFO uptake was not affected by DFO treatment.

  5. 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

    ... 64198-0001: 1. Aaron W. Anderson, Topeka, Kansas; Angela Anderson Swift, Overland Park, Kansas; Emery... trusts: Aaron W. Anderson Trust; Angela Anderson Swift Trust; Emery Kent Fager Trust; John Fontron Fager... Ellen Anderson Trust; Andrew Timothy Swift Trust; Sarah Ann Swift Trust; Samuel James Swift...

  6. 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…

  7. 75 FR 32932 - Combined Notice of Filings No. 1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    .... Applicants: Nexen Marketing, J. Aaron & Company. Description: Joint Petition for Temporary Waivers of... of Nexen Marketing U.S.A. Inc. and J. Aaron & Company. Filed Date: 05/21/2010. Accession Number... . To facilitate electronic service, persons with Internet access who will eFile a document and/or...

  8. 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.

  9. Chelation of thallium by combining deferasirox and desferrioxamine in rats.

    PubMed

    Saljooghi, Amir Shokooh; Babaie, Maryam; Mendi, Fatemeh Delavar; Zahmati, Maliheh; Saljooghi, Zoheir Shokouh

    2016-01-01

    The hypothesis that two known chelators deferasirox (4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing thallium from the body was tested in a new acute rat model. 7-week-old male Wistar rats received chelators: deferasirox (orally), DFO (intraperitoneal; i.p.), or deferasirox + DFO as 75 or 150 mg/kg dose half an hour after a single i.p. administration of 8 mg thallium/kg body weight in the form of chloride. Serum thallium concentration, urinary thallium, and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level, while DFO was more effective than deferasirox in enhancing urinary thallium excretion, deferasirox was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the DFO effect on thallium and DFO did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of thallium chelators. Urinary values were more useful because of the high variability of serum results.

  10. Deferoxamine alleviates liver fibrosis induced by CCl4 in rats.

    PubMed

    Mohammed, Aya; Abd Al Haleem, Ekram N; El-Bakly, Wesam M; El-Demerdash, Ebtehal

    2016-08-01

    Several chronic liver diseases can lead to the occurrence of hepatic fibrosis through the accumulation of iron, which causes induction of oxidative stress and consequently activation of fibrogenesis. The present study was designed to investigate the potential antifibrotic and anti-oxidant effects of deferoxamine (DFO), a well-known iron chelator in an experimental rat model of liver injury using carbon tetrachloride (CCl4 ). First, the potential effective dose of DFO was screened against CCl4 -induced acute hepatotoxicity. Then, rats were co-treated with DFO (300 mg/kg, i.p.) for 6 weeks starting from the third week of CCl4 induction of chronic hepatotoxicity. Liver function was assessed in addition to histopathological examination. Furthermore, oxidative stress and fibrosis markers were assessed. It was found that treatment of animals with DFO significantly counteracted the changes in liver function; histopathological lesions and hepatic iron deposition that were induced by CCl4 . DFO also significantly counteracted the CCl4 -induced lipid peroxidation increase and reduction in antioxidant activities of superoxide dismutase and glutathione peroxidase enzymes. In addition, DFO ameliorated significantly liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cells (HSCs) activation marker; alpha smooth muscle actin and transforming growth factor-beta (TGF-β). Together, these findings indicate that DFO possesses a potent antifibrotic effect due to its antioxidant properties that counteracted oxidative stress and lipid peroxidation and restored antioxidant enzymes activities as well as reducing HSCs activation and fibrogenesis.

  11. Functional and Structural Abnormalities in Deferoxamine Retinopathy: A Review of the Literature

    PubMed Central

    Di Nicola, Maura; Barteselli, Giulio; Dell'Arti, Laura; Ratiglia, Roberto; Viola, Francesco

    2015-01-01

    Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease. PMID:26167477

  12. 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. PMID:25620068

  13. 75 FR 1831 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP1000...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... October 14, 2009 (74 FR 58268-58269). Detailed ACRS meeting agendas and meeting transcripts are available... Federal Official (DFO), Mr. Peter Wen, (Telephone 301-415-2832, E-mail: Peter.Wen@nrc.gov ) five...

  14. 75 FR 28824 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Plant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-24

    ... published in the Federal Register on October 14, 2009 (74 FR 58268-58269). Detailed meeting agendas and... website cited above or by contacting the identified DFO. Moreover, in view of the possibility that...

  15. Latent fingermark development on a range of porous substrates using ninhydrin analogs--a comparison with ninhydrin and 1,8-diazofluoren.

    PubMed

    Berdejo, Stephanie; Rowe, Mark; Bond, John W

    2012-03-01

    Three relatively new reagents for developing latent fingermarks on porous substrates, 1,2-indandione (IND), 5-methylthioninhydrin (5-MTN), and lawsone, are compared with the more widely used ninhydrin and 1,8-diazofluoren (DFO). Developed latent fingermark visualization on 10 different substrates comprising colored papers, cardboard, and cellophane rather than conventional printer and writing/notepad paper is assessed using latent fingermark deposits from 48 donors. Results show improved fluorescent fingermark visualization using IND compared with DFO on a range of colored cardboards and thick white paper, thus extending the range of substrates known to yield improved visualization with IND. Adding zinc chloride to IND failed to yield any further improvement in fluorescent fingermark visualization. 5-MTN (with and without zinc chloride posttreatment) showed no improvement in visualization compared with ninhydrin and DFO although visible fingermarks were developed. Lawsone produced fluorescent visible fingermarks only with white substrates, which were inferior to those produced with DFO.

  16. 78 FR 58526 - Strategic Environmental Research and Development Program, Scientific Advisory Board; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... of the Secretary Strategic Environmental Research and Development Program, Scientific Advisory Board... Environmental Research and Development Program, Scientific Advisory Board (SAB). DATES: Tuesday, October 15... Designated Federal Officer (DFO) for the Strategic Environmental Research and Development Program,...

  17. 75 FR 13595 - Workforce Investment Act; Native American Employment and Training Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... Employment and Training Administration Workforce Investment Act; Native American Employment and Training... of the next meeting of the Native American Employment and Training Council (Council), as constituted... INFORMATION CONTACT: Mrs. Campbell, DFO, Indian and Native American Program, Employment and...

  18. 77 FR 22003 - Workforce Investment Act; Native American Employment and Training Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... Employment and Training Administration Workforce Investment Act; Native American Employment and Training... given of the next meeting of the Native American Employment and Training Council (Council), as..., DFO, Division of Indian and Native American Programs, Employment and Training Administration,...

  19. 78 FR 40144 - Governmentwide Travel Advisory Committee (GTAC); Upcoming Public Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ... ADMINISTRATION Governmentwide Travel Advisory Committee (GTAC); Upcoming Public Advisory Committee Meeting AGENCY... Governmentwide Travel Advisory Committee (GTAC) (the Committee), is a Federal Advisory Committee established in..., Designated Federal Officer (DFO), Governmentwide Travel Advisory Committee (GTAC), Office of...

  20. 77 FR 35102 - Commercial Space Transportation Advisory Committee; Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or email) by... formats: one hard copy with original signature or one electronic copy via email. An agenda will be...

  1. 78 FR 35259 - National Climate Assessment and Development Advisory Committee (NCADAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ..., Room 2E39, 300 E Street SW., Washington, DC 20546. Please check the Web site http://www.globalchange.... Individuals or groups planning to make a verbal presentation should contact the NCADAC DFO (...

  2. Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

    PubMed Central

    Zhang, Junye; Cui, Lei; Xu, Minhua; Zheng, Yuanli

    2014-01-01

    Objectives One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice. Methods DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations. Results The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR. Conclusions Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and

  3. Desferrioxamine enhances AIDS-associated Kaposi's sarcoma tumor development in a xenograft model.

    PubMed

    Simonart, Thierry; Boelaert, Johan R; Andrei, Graciela; van den Oord, Joost J; Degraef, Chantale; Hermans, Philippe; Noel, Jean-Christophe; Van Vooren, Jean-Paul; Heenen, Michel; De Clercq, Erik; Snoeck, Robert

    2002-07-10

    Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, we have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS). We have also shown that the iron chelator desferrioxamine (DFO) has a potent anti-KS activity in vitro, suggesting that it may represent a potential therapeutic approach for the treatment of KS. The present study was designed to investigate the effect of DFO on the growth of human KS xenografts in immunodeficient mice. Unexpectedly, we found that mice treated with DFO (400 mg/kg, 3 times weekly) (n = 30) exhibited a marked enhancement of tumor growth compared with control mice (n = 33) (230 +/- 134 mm(2) versus 143 +/- 70 mm p < 0.01). No enhancement of tumor growth was seen in mice treated with iron-saturated DFO. At least 2 findings suggest that this paradoxic pro-KS activity occurred independently of mice iron stores. First, treatment with DFO had only a marginal effect on ferritin and hematocrit levels. Second, induction of effective iron depletion by an iron-poor diet (6.7 mg iron/kg diet) (n = 23) did not have a deleterious effect on the growth of the KS xenografts. The lesions obtained from the DFO-treated animals exhibited a significantly decreased apoptotic index (p < 0.05), indicating that some antiapoptotic mechanism induced by DFO may be operating in vivo to favour tumor growth. In conclusion, our data show that DFO has a stimulatory effect on KS growth in immunodeficient mice, suggesting that this drug is not indicated in patients with KS.

  4. Exploring the "iron shuttle" hypothesis in chelation therapy: effects of combined deferoxamine and deferiprone treatment in hypertransfused rats with labeled iron stores and in iron-loaded rat heart cells in culture.

    PubMed

    Link, G; Konijn, A M; Breuer, W; Cabantchik, Z I; Hershko, C

    2001-08-01

    Although iron chelation therapy results in a significant improvement in well-being and life expectancy of thalassemic patients with transfusional iron overload, failure to achieve these goals in a substantial proportion of patients underlines the need for improved methods of treatment. In the present studies we used selective radioactive iron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to compare the source of iron chelated in vivo by deferoxamine (DFO) or by deferiprone (L1) and its mode of excretion, to examine the ability of DFO and L1 to remove iron directly from iron-loaded myocardial cells, and to examine the mechanism of their combined interaction through a possible additive or synergistic effect. Our results indicate that L1 given orally is 1.6 to 1.9 times more effective in rats, on a weight-per-weight basis, than parenteral DFO in promoting the excretion of storage iron from parenchymal iron stores but shows no advantage over DFO in promoting RE iron excretion. Simultaneous administration of DFO and L1 results in an increase in chelating effect that is additive but not synergistic. The magnitude of this additive effect is identical to an increase in the equivalent (weight or molar) dose of DFO alone rather than the sum of the separate effects of L1 and DFO. This finding is most probably the result of a transfer of chelated iron from L1 to DFO. These observations may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.

  5. 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.

  6. Interaction of Pseudomonas fluorescens with Eu(III) and Ce(IV) - Desferrioxamine Complexes

    NASA Astrophysics Data System (ADS)

    Yoshida, T.; Ozaki, T.; Ohnuki, T.; Francis, A.

    2002-12-01

    Naturally occurring chelating agents-, such as siderophores, are able to form complexes with actinides and enhance their solubility and mobility in the environment. Adsorption and/or biodegradation of chelated actinides by microorganisms are important processes which regulate their mobility in the natural environment. In this study, association of Eu(III), Ce(IV), and Fe(III) - desferrioxamine B (DFO) complexes with aerobic bacterium, Pseudomonas fluorescens (ATCC 55241), was investigated-, Eu(III) and Ce(IV) were used as analogues to trivalent and tetravalent actinides, respectively. When 20 μM of 1:1 Eu(III) - and Ce(IV) - DFO complexes were incubated with P. fluorescens in 0.1 M Tris-HCl buffer (pH = 7.3), the metals were removed from solution, with no change in DFO in solution. With decreasing metal/DFO molar ratio from 1 to 0.01, the accumulation of Eu(III) and Ce(IV) by P. fluorescens decreased. Kinetics study showed that accumulation of Eu(III) reached the maximum within 30 minutes, and then it decreased slightly with time. On the other hand, Ce(IV) accumulation proceeded in a parabolic process where the kinetics was slower than that of Eu(III) accumulation. In comparison to Eu(III) and Ce(IV), the removal of Fe(III) added as a DFO complex by P. fluorescens was not observed. The formation constants (log K) of Eu(III) - DFO and Fe(III) - DFO are reported to be 15 and 30.6, respectively. These results suggest that Eu(III) - DFO complex was dissociated in the presence of bacteria cells and was readily biosorbed.

  7. 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. PMID:16124306

  8. A Simple Small Size and Low Cost Sensor Based on Surface Plasmon Resonance for Selective Detection of Fe(III)

    PubMed Central

    Cennamo, Nunzio; Alberti, Giancarla; Pesavento, Maria; D'Agostino, Girolamo; Quattrini, Federico; Biesuz, Raffaela; Zeni, Luigi

    2014-01-01

    A simple, small size, and low cost sensor based on a Deferoxamine Self Assembled Monolayer (DFO-SAM) and Surface Plasmon Resonance (SPR) transduction, in connection with a Plastic Optical Fiber (POF), has been developed for the selective detection of Fe(III). DFO-SAM sensors based on appropriate electrochemical techniques can be frequently found in the scientific literature. In this work, we present the first example of a DFO-SAM sensor based on SPR in an optical fiber. The SPR sensing platform was realized by removing the cladding of a plastic optical fiber along half the circumference, spin coating a buffer of Microposit S1813 photoresist on the exposed core, and finally sputtering a thin gold film. The hydroxamate siderophore deferoxamine (DFO), having high binding affinity for Fe(III), is then used in its immobilized form, as self-assembled monolayer on the gold layer surface of the POF sensor. The results showed that the DFO-SAM-POF-sensor was able to sense the formation of the Fe(III)/DFO complex in the range of concentrations between 1 μm and 50 μm with a linearity range from 0 to 30 μm of Fe(III). The selectivity of the sensor was also proved by interference tests. PMID:24608007

  9. Role of deferoxamine on enzymatic stress markers in an animal model of Alzheimer's disease after chronic aluminum exposure.

    PubMed

    Esparza, José L; Garcia, Tania; Gómez, Mercedes; Nogués, M Rosa; Giralt, Montserrat; Domingo, José L

    2011-06-01

    The effect of the chelator deferoxamine (DFO) on the activity of enzymatic stress markers was assessed in amyloid beta peptide (AβPP) transgenic mice, an animal model of Alzheimer's disease, after oral aluminum (Al) exposure for 6 months. AβPP transgenic (Tg2576) and C57BL6/SJL wild-type mice of 5 months of age were fed a diet supplemented with Al lactate (1 mg of Al/g food). Four groups of Tg2576 and wild-type animals were used: control, Al only, DFO only, and Al plus DFO. Mice in the DFO-treated groups received also subcutaneous injections of 0.20 mmol/kg/d of this chelating agent twice a week until the end of the study at 11 months of age. The hippocampus, cerebellum, and cortex were removed and processed to examine a number of oxidative stress markers. Furthermore, the expression of Cu-Zn superoxide dismutase, glutathione reductase, and catalase was evaluated by quantitative reverse transcriptase polymerase chain reaction analysis. Aluminum levels in the hippocampus of Tg2576 mice were higher than those found in cerebellum and cortex, while the main oxidative effects were evidenced in the presence of DFO only. Oral Al exposure of AβPP transgenic mice would have some potential to promote pro-oxidant events, while DFO administration would not help in preventing these deleterious effects.

  10. Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity.

    PubMed

    Tian, Meng; Chen, Xi; Gu, Zhipeng; Li, Hao; Ma, Lu; Qi, Xin; Tan, Hong; You, Chao

    2016-06-25

    Deferoxamine is commonly used for iron-overload related diseases, its drawbacks such as instability and toxicity, however, significantly limited its utility in clinic. To address these issues, oxidation-responsive alginate-deferoxamine (Alg-DFO) conjugates were synthesized and their structure was characterized. The metabolism studies shown the conjugation of alginate significantly increased the stability of the DFO, with half-life more than 10 times longer than that of the free DFO. Moreover, the conjugates could not only quickly respond to oxidative stimuli and degradation, suggesting their potential to be cleared from the body by responding to iron-overload associated oxidative environment to avoid its accumulation and safety concern, but also protect iron binding capacity of the attached DFO from oxidation. The degradation mechanism for oxidative-response was proposed. In addition, the conjugates shown lower cytotoxicity compared to the free DFO. Taken together, the Alg-DFO conjugates synthesized in this work has promise for treating iron-overload related conditions. PMID:27083844

  11. Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity.

    PubMed

    Voest, E E; Neijt, J P; Keunen, J E; Dekker, A W; van Asbeck, B S; Nortier, J W; Ros, F E; Marx, J J

    1993-01-01

    A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study. PMID:8431969

  12. Local Injection of Deferoxamine Improves Neovascularization in Ischemic Diabetic Random Flap by Increasing HIF-1α and VEGF Expression

    PubMed Central

    Zhang, Yun; Xiong, Zhuyou; Li, Guangzao; Cui, Lei

    2014-01-01

    Background Although the systemic administration of deferoxamine (DFO) is protective in experimental models of normal ischemic flap and diabetic wound, its effect on diabetic flap ischemia using a local injection remains unknown. Objective To explore the feasibility of local injection of DFO to improve the survival of ischemic random skin flaps in streptozotocin (STZ)-induced diabetic mice. Methods Ischemic random skin flaps were made in 125 mice. Animals were divided into the DFO-treated (n = 20), PBS-treated (n = 16) and untreated (n = 16) groups. Surviving area, vessel density, and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were evaluated on the seventh day after local injection. Results The viability of DFO-treated flap was significantly enhanced, with increased regional blood perfusion and capillary density compared with those in the two control groups. Fluorescence-activated cell sorting (FACS) analysis demonstrated a marked increase in systemic Flk-1+/CD11b− endothelial progenitor cells (EPCs) in DFO-treated mice. Furthermore, the expression of VEGF and HIF-1α was increased not only in diabetic flap tissue, but also in dermal fibroblasts cultured under hyperglycemic and hypoxic conditions. Conclusions Local injection of DFO could exert preventive effects against skin flap necrosis in STZ-induced diabetic mice by elevating the expression of HIF-1α and VEGF, increased EPC mobilization, which all contributed to promote ischemic diabetic flap survival. PMID:24963878

  13. 75 FR 3904 - Change in Bank Control Notices; Acquisition of Shares of Bank or Bank Holding Companies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... Denney, Assistant Vice President) 1 Memorial Drive, Kansas City, Missouri 64198-0001: 1. Verlyn Joseph Herman, Jr., and Aaron Joseph Herman, both of Norton, Kansas; as members of a family group acting...

  14. 77 FR 21975 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ...,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 9, 2012. Aaron Siegel, Alternate... in the performance of their duties. Passwords and User IDs are used to control access to the...

  15. 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

  16. 77 FR 38782 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-29

    ..., cell telephone phone, email address, bank or credit union name, city, state, and zip code, ABA routing..., 1996, 61 FR 6427). Dated: June 26, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison...

  17. 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...

  18. 77 FR 13574 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: March 2, 2012. Aaron Siegel, Alternate OSD Federal.... Robin Patterson, Department of the Navy, DNS-36, 2000 Navy Pentagon, Washington, DC 20350-2000 or...

  19. 78 FR 45913 - Privacy Act of 1974; Systems of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: July 25, 2013. Aaron Siegel... Patron File Control System (August 19, 2009, 74 FR 41869) Changes: * * * * * System Location: Delete... and Civil Liberties Office Web site at...

  20. Tricky correlations

    NASA Astrophysics Data System (ADS)

    Wesson, John

    2016-05-01

    In reply to Aaron Iftikhar's article “Is physics just for the rich?” (Forum, March p27), which discussed disparities in the numbers of physics students from some geographic areas and socioeconomic groups.

  1. 76 FR 55057 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). ] Dated: August 29, 2011. Aaron Siegel, Alternate OSD...; 10 U.S.C. 4302, Enlisted Members of Army: Schools; 10 U.S.C. 1606, Educational Assistance for...

  2. 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.

  3. 76 FR 65184 - Federal Advisory Committee; Defense Health Board (DHB) Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-20

    ..., Falls Church, Virginia 22041-3206, (703) 681-8448, Ext. 1215, Fax: (703) 681-3317, Christine.bader@tma... at (703) 681- 8448 ext. 1280 by November 1, 2011. Dated: October 17, 2011. Aaron Siegel,...

  4. 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.

  5. 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)

  6. 76 FR 35195 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ..., (February 20, 1996, 61 FR 6427). Dated: June 8, 2011. Aaron Siegel, Alternate OSD Federal Register Liaison.... To the U.S. Citizenship and Immigration Services for use in making alien admission and...

  7. Medical Issues: Breathing

    MedlinePlus

    ... invasive ventilation. For long-term invasive ventilation, a tracheostomy tube is usually required. During a surgical procedure, ... soon as possible after diagnosis. Helpful Links Aaron's Tracheostomy webpage Acute Respiratory Illness Care Guidelines A Young ...

  8. 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

  9. 76 FR 58788 - Privacy Act of 1974; Systems of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-22

    ... property is required. This system also serves as a transportation management information system for Navy... (February 20, 2996, 61 FR 6427). Dated: September 19, 2011. Aaron Siegel, Alternate OSD Federal...

  10. 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...

  11. 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...

  12. 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. PMID:26978686

  13. 77 FR 4798 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-31

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: January 26, 2012. Aaron Siegel, Alternate OSD...) Networking Collaborative. System location: Alumni Relations, NWC Press and Events Department, Naval...

  14. 77 FR 40861 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-11

    ... (February 20, 1996, 61 FR 6427). Dated: July 5, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison...); and the opinions and evaluation of a 12-question performance questionnaire, represented by ``yes''...

  15. 78 FR 3407 - Information Collection; Submission for OMB Review, Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-16

    ... supporting documentation, may be obtained by calling CNCS, Aaron Olszewski, at (202) 606-6709 or email to... Service; and (2) Electronically by email to: smar@omb.eop.gov . SUPPLEMENTARY INFORMATION: The OMB...

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

    PubMed Central

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

    2015-01-01

    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. PMID:25294892

  17. DHA-enriched fish oil targets B cell lipid microdomains and enhances ex vivo and in vivo B cell function

    PubMed Central

    Gurzell, Eric A.; Teague, Heather; Harris, Mitchel; Clinthorne, Jonathan; Shaikh, Saame Raza; Fenton, Jenifer I.

    2013-01-01

    DHA is a n-3 LCPUFA in fish oil that generally suppresses T lymphocyte function. However, the effect of fish oil on B cell function remains relatively understudied. Given the important role of B cells in gut immunity and increasing human fish oil supplementation, we sought to determine whether DFO leads to enhanced B cell activation in the SMAD−/− colitis-prone mouse model, similar to that observed with C57BL/6 mice. This study tested the hypothesis that DHA from fish oil is incorporated into the B cell membrane to alter lipid microdomain clustering and enhance B cell function. Purified, splenic B cells from DFO-fed mice displayed increased DHA levels and diminished GM1 microdomain clustering. DFO enhanced LPS-induced B cell secretion of IL-6 and TNF-α and increased CD40 expression ex vivo compared with CON. Despite increased MHCII expression in the unstimulated ex vivo B cells from DFO-fed mice, we observed no difference in ex vivo OVA-FITC uptake in B cells from DFO or CON mice. In vivo, DFO increased lymphoid tissue B cell populations and surface markers of activation compared with CON. Finally, we investigated whether these ex vivo and in vivo observations were consistent with systemic changes. Indeed, DFO-fed mice had significantly higher plasma IL-5, IL-13, and IL-9 (Th2-biasing cytokines) and cecal IgA compared with CON. These results support the hypothesis and an emerging concept that fish oil enhances B cell function in vivo. PMID:23180828

  18. 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

  19. PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules

    PubMed Central

    GAROUSI, JAVAD; ANDERSSON, KEN G.; MITRAN, BOGDAN; PICHL, MARIE-LOUISE; STÅHL, STEFAN; ORLOVA, ANNA; LÖFBLOM, JOHN; TOLMACHEV, VLADIMIR

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide 89Zr. The 89Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160±60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, 89Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6±0.5% ID/g and tumour-to-blood ratio of 3.7±0.6 at 24 h after injection. 89Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody 89Zr-DFO-cetuximab at 48 h after injection. EGFR-expressing tumours were clearly visualized by microPET using 89Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 89Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo. PMID:26847636

  20. PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules.

    PubMed

    Garousi, Javad; Andersson, Ken G; Mitran, Bogdan; Pichl, Marie-Louise; Ståhl, Stefan; Orlova, Anna; Löfblom, John; Tolmachev, Vladimir

    2016-04-01

    Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide (89)Zr. The (89)Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160 ± 60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, (89)Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6 ± 0.5% ID/g and tumour-to-blood ratio of 3.7 ± 0.6 at 24 h after injection. (89)Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody (89)Zr-DFO-cetuximab at 48 h after injection. EGFR‑expressing tumours were clearly visualized by microPET using (89)Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 8(9)Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo. PMID:26847636

  1. Improvement of rat islet viability during transplantation: validation of pharmacological approach to induce VEGF overexpression.

    PubMed

    Langlois, A; Bietiger, W; Seyfritz, E; Maillard, E; Vivot, K; Peronet, C; Meyer, N; Kessler, L; Jeandidier, N; Pinget, M; Sigrist, S

    2011-01-01

    Delayed and insufficient revascularization during islet transplantation deprives islets of oxygen and nutrients, resulting in graft failure. Vascular endothelial growth factor (VEGF) could play a critical role in islet revascularization. We aimed to develop pharmacological strategies for VEGF overexpression in pancreatic islets using the iron chelator deferoxamine (DFO), thus avoiding obstacles or safety risks associated with gene therapy. Rat pancreatic islets were infected in vivo using an adenovirus (ADE) encoding human VEGF gene (4.10(8) pfu/pancreas) or were incubated in the presence of DFO (10 μmol/L). In vitro viability, functionality, and the secretion of VEGF were evaluated in islets 1 and 3 days after treatment. Infected islets or islets incubated with DFO were transplanted into the liver of syngenic diabetic rats and the graft efficiency was estimated in vivo by measuring body weight, glycemia, C-peptide secretion, and animal survival over a period of 2 months. DFO induced transient VEGF overexpression over 3 days, whereas infection with ADE resulted in prolonged VEGF overexpression lasting 14 days; however, this was toxic and decreased islet viability and functionality. The in vivo study showed a decrease in rat deaths after the transplantation of islets treated with DFO or ADE compared with the sham and control group. ADE treatment improved body weight and C-peptide levels. Gene therapy and DFO improved metabolic control in diabetic rats after transplantation, but this effect was limited in the presence of DFO. The pharmacological approach is an interesting strategy for improving graft efficiency during transplantation, but this approach needs to be improved with drugs that are more specific. PMID:21294962

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

    PubMed

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

    2014-05-21

    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 Olefinic=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.

  3. Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

    PubMed Central

    2015-01-01

    Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents. PMID:24814511

  4. 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. PMID:24501001

  5. 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

  6. 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

  7. Adenoviral infection or deferoxamine? Two approaches to overexpress VEGF in beta-cell lines.

    PubMed

    Langlois, Allan; Bietiger, William; Sencier, Marie-Christine; Maillard, Elisa; Pinget, Michel; Kessler, Laurence; Sigrist, Severine

    2009-07-01

    Rapid and adequate revascularization of transplanted islets is important for their survival and function during transplantation. Vascular endothelial growth factor (VEGF) could play a critical role with respect to islet revascularization. The aim of this study was to compare two strategies that are used to overexpress VEGF in beta-cells: (1) gene therapy through adenoviral infection and (2) a pharmacological approach using deferoxamine (DFO). beta-Cell lines from rat insulinoma (RINm5F) were either infected using an adenovirus encoding the gene of human VEGF 165 or incubated with DFO. One day after treatment, the viability of RINm5F cells was preserved with 10 micromol/L of DFO (103.95 +/- 5.66% toward control; n = 4). In addition, adenoviral infection maintained the viability of cells for all the concentrations used. In both treatments, overexpression of VEGF was in a comparable level. Finally, the ratio of Bax/Bcl-2 indicated that the apoptosis increased in infected beta-cells whereas treatment with DFO seems to be antiapoptotic. Our results suggest that the use of DFO could be a realistic approach to improve the vascularization of islets during transplantation. PMID:19527112

  8. 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.

  9. Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea.

    PubMed

    Vichinsky, Elliott; Torres, Marcela; Minniti, Caterina P; Barrette, Stephane; Habr, Dany; Zhang, Yiyun; Files, Beatrice

    2013-12-01

    We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long-term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea. Deferasirox (n = 135) and DFO (n = 68) had comparable safety profiles over 24 weeks. Adverse events (AEs) secondary to drug administration were reported in 26.7% of patients in the deferasirox cohort and 28.6% in the DFO cohort. Gastrointestinal disorders were more common with deferasirox, including diarrhea (10.4% versus 3.6%) and nausea (5.2% versus 3.6%). The most common AE in the DFO group was injection-site pain irritation, which occurred in 7% of patients. Acute renal failure occurred in one patient on deferasirox who was continued on medication despite progressive impairment of renal function parameters. Serum ferritin levels were reduced in both treatment groups. Patients continuing on deferasirox for up to 2 years demonstrated an absolute median serum ferritin decrease of -614 ng/mL (n = 96). Increasing deferasirox dose was associated with improved response and a continued manageable safety profile. Concomitant hydroxyurea administration (n = 28) did not appear to influence the efficacy, safety (including liver and kidney function), and pharmacokinetic parameters of deferasirox.

  10. 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.

  11. Combined chelation therapy with deferoxamine and deferiprone in β-thalassemia major: compliance and opinions of young thalassemic patients.

    PubMed

    Hatzipantelis, Emmanuel S; Karasmanis, Konstantinos; Perifanis, Vassilios; Vlachaki, Efthimia; Tziomalos, Konstantinos; Economou, Marina

    2014-01-01

    Treatment of β-thalassemia major (β-TM) includes regular blood transfusions and iron chelation with subcutaneous injection of deferoxamine (DFO). During the last decade, a new chelation agent, deferiprone (L1), was introduced. The purpose of our study was to determine the level of awareness/education regarding chelation therapy, the degree of compliance to this therapy and their views of L1 in patients with β-TM. A relevant questionnaire was administered to 36 patients (12-26 years old) who were on combination chelation therapy with both DFO and L1. The majority of patients was well aware/educated about chelation therapy (76.6%), was compliant with this therapy (74.4%) and had a positive view towards oral chelation (86.0%). In conclusion, most patients with β-TM who were on combination chelation therapy with DFO and L1 were satisfied with this treatment and this results in high compliance rates.

  12. 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.

  13. Dephosphorylation reactions of mono-, di-, and triesters of 2,4-dinitrophenyl phosphate with deferoxamine and benzohydroxamic acid.

    PubMed

    Medeiros, Michelle; Orth, Elisa S; Manfredi, Alex M; Pavez, Paulina; Micke, Gustavo A; Kirby, Anthony J; Nome, Faruk

    2012-12-01

    This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides. PMID:23167539

  14. Aluminum speciation studies in biological fluids. Part 5. A quantitative investigation of A1(III) complex equilibria with desferrioxamine, 2,3-dihydroxybenzoic acid, Tiron, CP20 (L1), and CP94 under physiological conditions, and computer-aided assessment of the aluminum-mobilizing capacities of these ligands in vivo.

    PubMed

    Desroches, S; Biron, F; Berthon, G

    1999-05-30

    While the involvement of environmental aluminum toxicity in the advent of senile dementias is still debated, acute aluminum toxicity of iatrogenic origin is well documented. So far, the only treatment available against it has been desferrioxamine (DFO), which induces major side effects. New drugs are thus highly desirable, and possible DFO substitutes have already been considered through various techniques. An important test for such new drugs is to assess their A1-mobilizing capacity in vivo. This can be done by computer-aided speciation provided formation constants for the corresponding A1(III) complexes are known beforehand. The present work reports an investigation of A1(III) complex equilibria with five sequestering ligands including DFO, and predicts the respective capacities of these to mobilize aluminum in vivo under normal and inflammatory conditions.

  15. Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

    PubMed Central

    2011-01-01

    Background Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. Methods HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. Results 39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested. No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Conclusions Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric. PMID:21992770

  16. Chelation of bismuth by combining desferrioxamine and deferiprone in rats.

    PubMed

    Tubafard, S; Fatemi, S J

    2008-05-01

    Consumption and production of bismuth compounds are increasing, however, a little information on the toxic effect and also the effective method in removal of bismuth compounds are available. The present research aimed to characterize the potential efficiency of two chelators after bismuth administration for 55A days following two dose levels of 20 and 40A mg/kg body weight daily to male rats. However, we found abnormalities after bismuth administration in clinical signs, such as body weight, kidneys and liver damages, a black line on gums and skin reactions. Furthermore, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing bismuth from the body was considered. Along this line, two known chelators deferiprone (1, 2-dimethy1-3-hydroxypyride-4-one, L(1)) and desferrioxamine (DFO) were chosen and tested in the acute rat model. Chelators were given orally (L(1)) or intraperitoneally (DFO) as a single or combined therapy for the period of a week. Doses of L(1) and DFO were 110A mg/kg body weight in experiments. Bismuth and iron concentrations in various tissues were determined by graphite furnace and flame atomic absorption spectrometry, respectively. The combined chelation therapy results show that DFO and L(1) are able to remove bismuth ions from the body, whereas iron concentration returned to the normal level and symptoms are also decreased. DFO was more effective than L1 in reducing bismuth concentration in tissues. The efficiency of DFOA +A L(1) is more than DFO or L(1) in removing bismuth from organs. Our results are indicative that the design procedure might be useful for preliminary in-vivo testing of the efficiency of chelating agents. Results of combined chelators' treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for efficiency of chelating agents in bismuth toxicity.

  17. Studies the alterations of biochemical and mineral contents in bone tissue of mus musculus due to aluminum toxicity and the protective action of desferrioxamine and deferiprone by FTIR, ICP-OES, SEM and XRD techniques

    NASA Astrophysics Data System (ADS)

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

    The present study has attempt to analyze the changes in the biochemical and mineral contents of aluminum intoxicated bone and determine the protective action of desferrioxamine (DFO) and deferiprone (DFP) by using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP-OES), and scanning electron microscopy (SEM) techniques for four groups of animals such as control (Group I), aluminum intoxicated (Group II), Al + DFP (Group III) and Al + DFO + DFP (Group IV) treated groups respectively. The FTIR spectra of the aluminum intoxicated bone showed significant alteration in the biochemical constituents. The bands ratio at I1400/I877 significantly decreased from control to aluminum, but enhanced it by Al + DFP to Al + DFO + DFP treated bone tissue for treatments of 16 weeks. This result suggests that DFO and DFP are the carbonate inhibitor, recovered from chronic growth of bone diseases and pathologies. The alteration of proteins profile indicated by Amide I and Amide II, where peak area values decreased from control to aluminum respectively, but enhanced by treated with DFP (p.o.) and DFO + DFP (i.p.) respectively. The XRD analysis showed a decrease in crystallinity due to aluminum toxicity. Further, the Ca, Mg, and P contents of the aluminum exposed bone were less than those of the control group, and enhanced by treatments with DFO and DFP. The concentrations of trace elements were found by ICP-OES. Therefore, present study suggests that due to aluminum toxicity severe loss of bone minerals, decrease in the biochemical constituents and changes in the surface morphology.

  18. Hydroxamate-based iron chelators: combinatorial syntheses of desferrioxamine B analogues and evaluation of binding affinities.

    PubMed

    Poreddy, Amruta R; Schall, Otto F; Osiek, Todd A; Wheatley, James R; Beusen, Denise D; Marshall, Garland R; Slomczynska, Urszula

    2004-01-01

    This article describes the solid-phase combinatorial methods developed for the synthesis of polyhydroxamate-based siderophores. This strategy was applied to generate several libraries of structural DFO (1a) analogues that include DFO variants, non-amide analogues, C-terminal modified analogues, reverse-amide analogues, and hybrid analogues. To assess the relative iron-binding affinities of these compounds, a high-throughput spectrophotometric screening method based on competition with 8-hydroxyquinoline-5-sulfonic acid was developed. Some of the promising candidates containing various terminal functional groups were identified and prepared on large scale to enable future studies in animal models for iron-overload diseases.

  19. 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.

  20. 78 FR 37597 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Power...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    .../or written comments should notify the Designated Federal Official (DFO), Peter Wen (Telephone 301-415-2832 or Email: Peter.Wen@nrc.gov ) five days prior to the meeting, if possible, so that appropriate... were published in the Federal Register on October 18, 2012, (77 FR 64146- 64147). Detailed...

  1. 77 FR 52372 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on Plant License...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... Official (DFO), Peter Wen (Telephone 301-415-2832 or Email: Peter.Wen@nrc.gov ) five days prior to the..., (76 FR 64126- 64127). Detailed meeting agendas and meeting transcripts are available on the NRC Web..., MD. After registering with security, please contact Mr. Theron Brown (Telephone 240-888-9835) to...

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    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... comments should notify the Designated Federal Official (DFO), Peter Wen (Telephone 301-415-2832 or E-mail: Peter.Wen@nrc.gov ) five days prior to the meeting, if possible, so that appropriate arrangements can be... published in the Federal Register on October 21, 2010, (75 FR 65038- 65039). Detailed meeting agendas...

  3. 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

    2015-01-01

    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.

  4. 78 FR 65008 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Evolutionary...

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    ...) will hold a meeting on November 6, 2013, Room T-2B1, 11545 Rockville Pike, Rockville, Maryland. The..., presenters should provide the DFO with a CD containing each presentation at least thirty minutes before the... published in the Federal Register on October 18, 2012 (77 FR 64146- 64147). Detailed meeting agendas...

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    ...; Notice of Meeting The ACRS Subcommittee on AP1000 will hold a meeting on December 1, 2010, Room T-2B1... timeframe, presenters should provide the DFO with a CD containing each presentation at least thirty minutes... were published in the Federal Register on October 21, 2010 (75 FR 65038- 65039). Detailed...

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    ... & PRA The ACRS Subcommittee on Reliability & PRA will hold a meeting on April 24, 2013, Room T-2B1..., presenters should provide the DFO with a CD containing each presentation at least thirty minutes before the... published in the Federal Register on October 18, 2012, (77 FR 64146- 64147). Detailed meeting agendas...

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    ... take place on Thursday, July 26, 2012, from 11 a.m. to 12:30 p.m. EST. This meeting may close early if all business is finished. Oral comments may be made at the July 26 meeting, but requests to make oral... meet via telephone conference, on July 26, 2012. The Public may participate by contacting the DFO...

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    ... (g) MODU Crane regulations (h) Fire Suppression Systems/CO 2 NPRM FR Feb. 24, 2010 (5) STCW... Commander P.W. Clark, Designated Federal Officer (DFO), Commandant (CG- 5222), U.S. Coast Guard, 2100 Second...-2010-0127, at http://www.regulations.gov . FOR FURTHER INFORMATION CONTACT: Commander P.W....

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    ... published in the Federal Register on October 18, 2012, (77 FR 64146- 64147). Detailed meeting agendas and... comments should notify the Designated Federal Official (DFO), Peter Wen (Telephone 301-415-2832 or Email: Peter.Wen@nrc.gov ) five days prior to the meeting, if possible, so that appropriate arrangements can...

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    ... ACRS meetings were published in the Federal Register on October 14, 2009 (74 FR 58268- 58269). Detailed... oral statements and/or written comments should notify the Designated Federal Official (DFO), Peter Wen (Telephone 301-415-2832 or E-mail ( Peter.Wen@nrc.gov ) five days prior to the meeting, if possible, so...

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    ..., 2012, 77 FR 23277, is cancelled. Instead, members of the Committee will meet on May 8, 2012, solely to share information and discuss preparations for the Wekiva Wild and Scenic River Plan Dedication Ceremony... INFORMATION CONTACT: Jaime Doubek-Racine, DFO, Wekiva Wild and Scenic River, RTCA Program, Florida...

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    ... Warrant Officer David Chapman, Assistant to the DFO of Lower Mississippi River Waterway Safety Advisory... (RNA); Gulf Intracoastal Waterway, Inner Harbor Navigation Canal, Harvey Canal, Algiers Canal, New Orleans, LA published in the Federal Register, Vol. 75, page 32275 (75 FR 32275), on June 8, 2010,...

  7. 75 FR 32229 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on ABWR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-07

    ... Subcommittee on Advanced Boiling Water Reactor (ABWR) will hold a meeting on June 23-24, 2010, Room T-2B3... arrangements can be made. Thirty-five hard copies of each presentation or handout should be provided to the DFO... were published in the Federal Register on October 14, 2009 (74 FR 58268-58269). Detailed...

  8. 76 FR 78281 - Medicare Program; First Semi-Annual Meeting of the Advisory Panel on Hospital Outpatient Payment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... cell phones, are subject to physical inspection. The public may enter the building 30 to 45 minutes..., address, phone, and email addresses for all presenters and a contact person that can answer any questions... Officier (DFO): Paula Smith, 7500 Security Boulevard, Mail Stop C4-05-17, Woodlawn, MD 21244-1850....

  9. 78 FR 22918 - Advisory Committee on Reactor Safeguards (RS); Meeting of the Acrs Subcommittees on Reliability...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... COMMISSION Advisory Committee on Reactor Safeguards (RS); Meeting of the Acrs Subcommittees on Reliability and PRA; Revision to Notice of Meetings The ACRS Subcommittee on Reliability and PRA originally... (DFO), John Lai (Telephone 301-415-5197 or Email: John.Lai@nrc.gov ) between 8:15 a.m. and 5:00...

  10. 76 FR 65183 - National Oceanic and Atmospheric Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-20

    ... science and information pertaining to current and future impacts of climate. Time and Date: The meeting... submitted verbal or written statements. In general, each individual or group making a verbal presentation... presentation. Written comments should be received in the NCADAC DFO's Office by November 10, 2011 to...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 75 FR 36715 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Planning and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... and/or written comments should notify the Designated Federal Official (DFO), Jorge Cruz-Ayala (Telephone 301-415-0269 or E-mail ( Jorge.Cruz-Ayala@nrc.gov ) five days prior to the meeting, if possible... ACRS meetings were published in the Federal Register on October 14, 2009, (74 FR 58268-58269)....

  18. 75 FR 25199 - Medbow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-07

    ... at Forest Supervisor's Office, 2468 Jackson Street, Laramie, Wyoming. Written comments should be sent to Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie, Wyoming 82070. Comments may also be sent via e... may inspect comments received at the Forest Supervisor's Office, 2468 Jackson Street, Laramie,...

  19. 76 FR 12016 - MedBow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ... sent to Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie, Wyoming 82070. Comments may also be sent via... public may inspect comments received at the Forest Supervisor's Office, 2468 Jackson Street, Laramie... those sessions. Dated: February 25, 2011. Phil Cruz, Forest Supervisor. BILLING CODE 3410-11-P...

  20. 75 FR 39201 - MedBow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-08

    ... Springs, Colorado. Written comments should be sent to Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie... Office, 2468 Jackson Street, Laramie, Wyoming. FOR FURTHER INFORMATION CONTACT: Diann Ritschard, RAC... have the opportunity to address the Comittee at those sessions. Dated: July 1, 2010. Phil Cruz,...

  1. 75 FR 52304 - MedBow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-25

    ... Service Office, 5556 State Highway 130, Saratoga, Wyoming. Written comments should be sent to Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie, Wyoming 82070. Comments may also be sent via e-mail to pcruz@fs... comments received at the Forest Supervisor's Office, 2468 Jackson Street, Laramie, Wyoming. FOR...

  2. 76 FR 41195 - Medbow-Routt Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... will be held at Forest Supervisor's Office, 2468 Jackson Street, Laramie, Wyoming. Written comments should be sent to Phil Cruz, RAC DFO, 2468 Jackson Street, Laramie, Wyoming 82070. Comments may also be... public may inspect comments received at the Forest Supervisor's Office, 2468 Jackson Street,...

  3. Longitudinal analysis of heart and liver iron in thalassemia major patients according to chelation treatment.

    PubMed

    Danjou, F; Origa, R; Anni, F; Saba, L; Cossa, S; Podda, G; Galanello, R

    2013-10-01

    Iron chelators and nuclear magnetic resonance imaging (MRI) techniques for assessing iron loading in liver and heart have greatly improved survival of thalassemic patients suffering iron overload-associated cardiomyopathy. However, the correlation between liver iron concentration and myocardial siderosis is ambiguous. Using an objective metric of time delay, scientists have demonstrated a lag in the loading and unloading of cardiac iron with respect to that of the liver. In the present study, we further tested this hypothesis with different chelation treatments. We analyzed the effect of three chelating treatment approaches on liver and cardiac iron content in 24 highly compliant patients who underwent 3 or more MRIs under each chelation treatment. Of the 84 MRIs considered, 32 were performed on deferoxamine (DFO - 8 patients), 24 on deferiprone (DFP - 7 patients), and 28 on combined therapy (DFO+DFP - 9 patients). In patients treated with DFO, changes in cardiac iron significantly lagged changes in liver iron but the opposite pattern was observed in patients treated with DFP (p=0.005), while combined therapy showed a pattern in-between DFO and DFP. We conclude that the temporality of changes of cardiac and liver iron is chelator-dependent, so that chelation therapy can be tailored to balance iron elimination from the liver and the heart.

  4. 75 FR 67958 - Blue Ribbon Commission on America's Nuclear Future

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Ribbon Commission on America's Nuclear Future AGENCY: Office of Nuclear Energy, Department of Energy... CommissionDFO@nuclear.energy.gov . Additional information will be available at http://www.brc.gov... cycle policies that have been established by other leading nuclear energy nations. The Commission...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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 ....

  12. 75 FR 44306 - Fifth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ..., Approve/ Review Meeting 4 Summary, RTCA Paper No. 099-10/SC223-009). Welcome from NASA Glenn Research Center Management: Dr. Gary Seng. Special Committee Leadership. Designated Federal Official (DFO): Mr...: The meeting will be held at the NASA Glenn Research Center, 21000 Brookpark Road, Cleveland, OH...

  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. 77 FR 36273 - Notification of a Joint Public Meeting of the Chartered Science Advisory Board and Chartered...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ... AGENCY Notification of a Joint Public Meeting of the Chartered Science Advisory Board and Chartered Board.... SUMMARY: The Environmental Protection Agency (EPA) Science Advisory Board (SAB) Staff Office announces a... concerning the meeting may contact Dr. Angela Nugent, Designated Federal Officer (DFO), EPA Science...

  15. 75 FR 47281 - Federal Advisory Committee; Military Leadership Diversity Commission (MLDC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ... Federal Advisory Committee; Military Leadership Diversity Commission (MLDC) AGENCY: Office of the Under... that the Military Leadership Diversity Commission (MLDC) will meet August 23-25, 2010, in Richmond, VA... p.m. DFO opens the meeting. Presentation of recommendations for diversity leadership and...

  16. 75 FR 8310 - Federal Advisory Committee; Military Leadership Diversity Commission (MLDC); Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... of the Secretary Federal Advisory Committee; Military Leadership Diversity Commission (MLDC....150, the Department of Defense announces that the Military Leadership Diversity Commission (MLDC) will... leadership and training Open Discussion on career development: branching and assignments 12 p.m. DFO...

  17. 75 FR 24927 - Federal Advisory Committee; Military Leadership Diversity Commission (MLDC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ... of the Secretary Federal Advisory Committee; Military Leadership Diversity Commission (MLDC) AGENCY..., the Department of Defense announces that the Military Leadership Diversity Commission (MLDC) will meet... organizations responsible for diversity leadership and training 11:45 a.m. DFO recesses the meeting 1...

  18. 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

  19. 75 FR 8374 - Medicare Program; Meeting of the Practicing Physicians Advisory Council, March 8, 2010; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... CONTACT: Kelly Buchanan, DFO, (410) 786-6132, or e-mail PPAC_hhs@cms.hhs.gov . News media representatives... INFORMATION: I. Background In FR Doc. 2010-1333 of January 22, 2010 (75 FR 3743), there were a number of... section III. of this notice. III. Correction of Errors In FR Doc. 2010-1333 of January 22, 2010 (75...

  20. 78 FR 42944 - Notification of a Public Meeting of the Great Lakes Advisory Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-18

    ... AGENCY Notification of a Public Meeting of the Great Lakes Advisory Board AGENCY: Environmental... public meeting and teleconference of the Great Lakes Advisory Board (GLAB). The meeting will be held on... Cestaric, Designated Federal Officer (DFO) for the Great Lakes Advisory Board by telephone at (312)...

  1. 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

    ... AGENCY Meeting of the Local Government Advisory Committee and Small Community Advisory Subcommittee AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The U.S. EPA's Local Government...., Chicago, Illinois. FOR FURTHER INFORMATION CONTACT: Paula Zampieri, DFO for the Local Government...

  2. 76 FR 22394 - Meeting of the Local Government Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ... AGENCY Meeting of the Local Government Advisory Committee AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The U.S. EPA's Local Government Advisory Committee (LGAC) will meet May 18-19... FURTHER INFORMATION CONTACT: Paula Zampieri, DFO for the Local Government Advisory Committee (LGAC)...

  3. Development of fingermark on the surface of fired cartridge casing using amino acid sensitive reagents: Change of viewpoint.

    PubMed

    Hong, Sungwook; Han, Aleum

    2016-09-01

    Four amino acid sensitive fingermark enhancement reagents (ninhydrin, 5-methylthioninhydrin (5-MTN), 1,8-diazafloren-9-one (DFO), 1,2-indandione (1,2-IND) were used for the development of fingermark on the surface of brass. The reagents were used for the detection of a trace amount of metallic ion on the surface of cartridge casings to develop latent fingermarks. Ninhydrin-l-alanine (NIN-ALA), 5-MTN-l-alanine (MTN-ALA), DFO-l-alanine (DFO-ALA), 1,2-IND-l-alanine (IND-ALA) complexes were prepared and applied to the fired cartridge casings, for the further enhancement of fingermarks developed by corrosion on the surface of brass. Of the four complexes, NIN-ALA and MTN-ALA complexes induced color changes to enhance fingermarks on fired cartridge casings, but photoluminescence was not observed. About 31% of cartridge casings treated with MTN-ALA showed enhanced fingermarks. DFO-ALA and IND-ALA did not show any enhancement of fingermarks. PMID:27235594

  4. 78 FR 48151 - Defense Health Board; Notice of Federal Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ... statement until the next open meeting. The DFO will review all timely submissions with the DHB President and... of 1972 (5 U.S.C., Appendix, as amended), the Government in the Sunshine Act of 1976 (5 U.S.C. 552b... and deliberate pending and new issues before the Board. Agenda Pursuant to 5 U.S.C. 552b, as...

  5. 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...

  6. 75 FR 38866 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ...: One hard copy with original signature or one electronic copy via e-mail. An agenda will be posted on... listed below) by phone or e-mail for the teleconference call in number. The proposed agenda for this... contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail) by July 15,...

  7. 76 FR 621 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-05

    ... contact Susan Lender, DFO, (the Contact Person listed below) by phone or e-mail for the teleconference... (mail or e-mail) by January 14, 2011, so that the information can be made available to COMSTAC members... should be supplied in the following formats: one hard copy with original signature or one electronic...

  8. 76 FR 4743 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ... following formats: One hard copy with original signature or one electronic copy via e-mail. An agenda will... listed below) by phone or e-mail for the teleconference call in number. The proposed agenda for this... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail)...

  9. 76 FR 41323 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... formats: One hard copy with original signature or one electronic copy via e-mail. An agenda will be posted...-mail for the teleconference call in number. The proposed agenda for this teleconference is the single... contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail) by August 4,...

  10. 75 FR 51332 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... following formats: One hard copy with original signature or one electronic copy via e-mail. An agenda will... listed below) by phone or e-mail for the teleconference call-in number. The proposed agenda for this... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail)...

  11. 75 FR 52058 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... following formats: one hard copy with original signature or one electronic copy via e-mail. An agenda will... listed below) by phone or e-mail for the teleconference call in number. The proposed agenda for this... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail)...

  12. 76 FR 15041 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... formats: One hard copy with original signature or one electronic copy via e-mail. An agenda will be posted... listed below) by phone or e-mail for the teleconference call in number. The proposed agenda for this... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or e-mail)...

  13. 76 FR 18586 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Reliability...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... reliability analysis (HRA) models as well as fire HRA guidelines in NUREG-1921, Fire Human Reliability... comments should notify the Designated Federal Official (DFO), John Lai (Telephone 301-415-5197 or E-mail... published in the Federal Register on October 21, 2010, (75 FR 65038-65039). Detailed meeting agendas...

  14. 75 FR 66401 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on U.S...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-28

    ... ACRS meetings were published in the Federal Register on October 14, 2009 (74 FR 58268-58269). Detailed... and/or written comments should notify the Designated Federal Official (DFO), Neil Coleman (Telephone 301-415-7656 or E-mail: Neil.Coleman@nrc.gov ) five days prior to the meeting, if possible, so...

  15. 78 FR 9730 - Boston Harbor Islands Advisory Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... Jacobson, DFO, Boston Harbor Islands National Recreation Area, 408 Atlantic Avenue, Suite 228, Boston, MA 02110; telephone (617) 223-8669; email Bruce_Jacobson@nps.gov . SUPPLEMENTARY INFORMATION: This meeting... Official for the Boston Harbor Islands Advisory Council, Bruce Jacobson, by mail at 408 Atlantic...

  16. 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

  17. 76 FR 3919 - National Offshore Safety Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ..., originally scheduled for Wednesday, January 12, 2011, from 11 a.m. to 12:30 p.m. EST, was cancelled due to... teleconference meeting will take place on Wednesday, February 9, 2011, from 11 a.m. to 12:30 p.m. EST. This... EST. FOR FURTHER INFORMATION CONTACT: Commander P.W. Clark, Designated Federal Officer (DFO) of...

  18. 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...

  19. 75 FR 33616 - Science Advisory Board Staff Office; Notification of a Public Meeting of the Science Advisory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-14

    ... AGENCY Science Advisory Board Staff Office; Notification of a Public Meeting of the Science Advisory...: Notice. SUMMARY: The EPA Science Advisory Board (SAB) Staff Office announces a public meeting of the SAB... Federal Officer (DFO), EPA Science Advisory Board (1400F), 1200 Pennsylvania Avenue, NW., Washington,...

  20. 75 FR 28824 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on APWR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-24

    ... subject meeting shall be as follows: Monday, June 7, 2010, 8:30 a.m.-5 p.m. The Subcommittee will review... Designated Federal Official (DFO), Mr. Neil Coleman (Telephone 301-415-7656 or e-mail Neil.Coleman@NRC.gov... Register on October 14, 2009 (74 FR 58268-58269). Detailed meeting agendas and meeting transcripts...

  1. 78 FR 8202 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on US-APWR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... and/or written comments should notify the Designated Federal Official (DFO), Girija Shukla (Telephone... ACRS meetings were published in the Federal Register on October 18, 2012, (77 FR 64146- 64147.../reading-rm/doc-collections/acrs . Information regarding topics to be discussed, changes to the...

  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. 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. Tripodal tris(hydroxypyridinone) ligands for immunoconjugate PET imaging with 89Zr4+: comparison with desferrioxamine-B† †Electronic supplementary information (ESI) available: 1H and 13C NMR data, reverse phase HPLC and size exclusion HPLC chromatograms, phosphoimages of ITLC plates, ex vivo biodistribution data. See DOI: 10.1039/c4dt02978j Click here for additional data file.

    PubMed Central

    Meszaros, Levente K.; Paterson, Brett M.; Berry, David J.; Cooper, Maggie S.; Ma, Yongmin; Hider, Robert C.; Blower, Philip J.

    2015-01-01

    Due to its long half-life (78 h) and decay properties (77% electron capture, 23% β+, E max = 897 keV, E av = 397 keV, Eγ = 909 keV, Iγ = 100%) 89Zr is an appealing radionuclide for immunoPET imaging with whole IgG antibodies. Derivatives of the siderophore desferrioxamine-B (H3DFO) are the most widely used bifunctional chelators for coordination of 89Zr4+ because the radiolabeling of the resulting immunoconjugates is rapid under mild conditions. 89Zr-DFO complexes are reportedly stable in vitro but there is evidence that 89Zr4+ is released in vivo, and subsequently taken up by the skeleton. We have evaluated a novel tripodal tris(hydroxypyridinone) chelator, H3CP256 and its bifunctional maleimide derivative, H3YM103, for coordination of Zr4+ and compared the NMR spectra, and the 89Zr4+ radiolabeling, antibody conjugation, serum stability and in vivo distribution of radiolabelled immunoconjugates with those of H3DFO and its analogues. H3CP256 coordinates 89Zr4+ at carrier-free concentrations forming [89Zr(CP256)]+. Both H3DFO and H3CP256 were efficiently radiolabelled using [89Zr(C2O4)4]4– at ambient temperature in quantitative yield at pH 6–7 at millimolar concentrations of chelator. Competition experiments demonstrate that 89Zr4+ dissociates from [89Zr(DFO)]+ in the presence of one equivalent of H3CP256 (relative to H3DFO) at pH 6–7, resulting largely in [89Zr(CP256)]+. To assess the stability of H3DFO and H3YM103 immunoconjugates radiolabelled with 89Zr, maleimide derivatives of the chelators were conjugated to the monoclonal antibody trastuzumab via reduced cysteine side chains. Both immunoconjugates were labelled with 89Zr4+ in >98% yield at high specific activities and the labeled immunoconjugates were stable in serum with respect to dissociation of the radiometal. In vivo studies in mice indicate that 89Zr4+ dissociates from YM103-trastuzumab with significant amounts of activity becoming associated with bones and joints (25.88 ± 0.58% ID g–1 7

  5. 77 FR 56625 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... individual and information migrated from the agency Human Resources Data Base.'' * * * * * BILLING CODE 5001..., 1996, 61 FR 6427). Dated: September 10, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. LDIA 06-0004 System name: Recall Rosters (April 16, 2010, 75 FR...

  6. 77 FR 2515 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... System (MARS) Member Records (April 12, 1999, 64 FR 17636). * * * * * Changes: Delete entry and replace... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: January 12, 2012. Aaron Siegel, Alternate OSD... individual name, MARS call sign, amateur call sign, mailing address, Federal Communications license...

  7. 78 FR 37800 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ..., Departmental Regulations; SECNAVINST 5300.26D, Department of the Navy (DON) Policy on Sexual Harassment... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 19, 2013. Aaron Siegel, Alternate OSD Federal... Information System (May 9, 2003, 68 FR 24959). Changes: * * * * * System name: Delete entry and replace...

  8. 77 FR 16019 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... (February 20, 1996, 61 FR 6427). Dated: March 13, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison... matters of civil disturbance, disaster relief, and civil defense and emergency action; records concern... conditions. Also covers records on nuclear accidents and incidents. Legal Services: Judiciary boards...

  9. 76 FR 54743 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-02

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: August 29, 2011. Aaron Siegel, Alternate OSD Federal... participation and support in matters of civil disturbance, disaster relief, and civil defense and emergency... practices and conditions. Also covers records on nuclear accidents and incidents. Legal Services:...

  10. "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…

  11. 77 FR 21973 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... assurance protocols. The user can also restrict access to his personal data by selecting which type of... change, including any personal identifiers or contact information. FOR FURTHER INFORMATION CONTACT: Ms..., 1996, 61 FR 6427). Dated: April 9, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison...

  12. 77 FR 34357 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... (February 20, 1996, 61 FR 6427). Dated: June 5, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison..., 2008, 73 FR 12711) Changes: * * * * * System location: Delete entry and replace with ``Primary location... the facilities themselves, access to paper and computer printouts are controlled by...

  13. 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…

  14. 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…

  15. 77 FR 21974 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 9, 2012. Aaron Siegel... Intelligence Virtual University (JIVU II) (March 24, 2008, 73 FR 15496) Changes: * * * * * System locations... on a need- to-know basis in the performance of their duties. Passwords and User IDs are used...

  16. 78 FR 47308 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: July 31, 2013. Aaron Siegel, Alternate OSD Federal..., 2010, 75 FR 26201) Changes * * * * * Categories of individuals covered by the system: Delete entry and... basis in the performance of their duties. Passwords and User IDs are used to control access to...

  17. 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…

  18. 78 FR 14284 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... containing employee data; name, Social Security Number (SSN), time and attendance, and work schedule; and...,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: February 28, 2013. Aaron Siegel... Management Information System (DMIS) (November 9, 2005, 70 FR 67995). Changes: * * * * * System...

  19. 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…

  20. 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…

  1. 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…

  2. Adventure Learning: Situating Learning in an Authentic Context

    ERIC Educational Resources Information Center

    Doering, Aaron

    2007-01-01

    In this paper, Aaron Doering describes an adventure learning project that connected students to explorers and researchers participating in a trans-Arctic dogsled expedition. Adventure learning (AL) uses a hybrid online educational environment to provide students with opportunities to explore real-world issues through authentic learning…

  3. 78 FR 73509 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... Reserve Component Soldiers and Units, and Air Force, Navy and Marine Corps requesting and scheduling ``Army unit'' required training before entering into CENTCOM's theater of operation. DATES: This proposed... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: December 2, 2013. Aaron Siegel, Alternate...

  4. 78 FR 74122 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: December 5, 2013. Aaron Siegel, Alternate OSD...'s Records (December 30, 2008, 73 FR 79849). Changes: * * * * * Categories of individuals covered by... inquiries to AF A4LE, Pentagon, Washington, DC 20330-1040. For verification purposes, individual...

  5. 77 FR 25991 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... system: Resident and distance learning course and personnel data to include individual's name, scheduling... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 27, 2012. Aaron Siegel, Alternate OSD...- paced training and education. GuardU provides a learning content management and delivery platform...

  6. 78 FR 73515 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... address, home/ work or mobile phone numbers, home/work email address, record number, military grade/rate..., Washington, DC 20350-2000, or by phone at (202) 685-6545. SUPPLEMENTARY INFORMATION: The Department of the..., 1996, 61 FR 6427). ] Dated: December 3, 2013. Aaron Siegel, Alternate OSD Federal Register...

  7. 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 as a Model for Closely Watching…

  8. 78 FR 73512 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ..., 1996, 61 FR 6427). Dated: December 3, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. N05880-2 System Name: Admiralty Claims Files (May 9, 2003, 68 FR 24959... asserted for and against the Department of the Navy involving death, personal injury, property damage,...

  9. 78 FR 34354 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 3, 2013. Aaron Siegel, Alternate OSD Federal... Systems (September 21, 2006, 71 FR 55173). Changes: * * * * * System location: Delete entry and replace... information. FOR FURTHER INFORMATION CONTACT: Ms. Robin Patterson, Head, PA/FOIA Office (DNS-36),...

  10. 78 FR 37801 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 19, 2013. Aaron Siegel, Alternate OSD Federal... System (ODIS) (July 26, 2010, 75 FR 43500). Changes: * * * * * Categories of records in the system... information. FOR FURTHER INFORMATION CONTACT: Ms. Robin Patterson, Head, PA/FOIA Office (DNS-36),...

  11. 77 FR 27745 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: May 8, 2012. Aaron Siegel, Alternate OSD Federal...) Records (December 12, 2008, 73 FR 75692). Changes: * * * * * Categories of individuals covered by the.... Robin Patterson, Department of the Navy, DNS-36, 2000 Navy Pentagon, Washington, DC 20350-2000 or...

  12. 78 FR 44102 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: July 18, 2013. Aaron Siegel, Alternate OSD Federal... Transportation Benefit Program (March 7, 2012, 77 FR 13574) Changes: * * * * * Categories of records in the... (DNS-36), Department of the Navy, 2000 Navy Pentagon, Washington, DC 20350-2000, or by phone at...

  13. 76 FR 82283 - Privacy Act of 1974; Systems of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ...,' dated December 12, 2000, 65 FR 239. Dated: December 27, 2011. Aaron Siegel, Alternate OSD Federal..., 2010, 75 FR 2514). Changes: * * * * * Categories of individuals covered by the system: Delete entry and... (NSA) is proposing to alter a system of records in its inventory of records systems subject to...

  14. 77 FR 56628 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: September 10, 2012. Aaron Siegel.... Kris Grein, National Security Agency/Central Security Service (NSA/CSS), Freedom of Information Act and... Government who wrote to NSA on behalf of the constituent and who use it to respond to the constituent....

  15. 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,…

  16. 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…

  17. 76 FR 28964 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... (February 20, 1996, 61 FR 6427). Dated: May 15, 2011. Aaron Siegel, Alternate OSD Federal Register Liaison... terminals and rooms, guards, personnel screening, or visitor registers. eMarine Family Readiness (FR) Web...Marine Family Readiness (FR) Web site--The eMarine system is a protected network that will employ...

  18. 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…

  19. 76 FR 35197 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... Maintaining Records About Individuals,'' February 20, 1996, 61 FR 6427. Dated: June 7, 2011. Aaron Siegel... Correspondence Course Program (ACCP) (July 25, 2008, 73 FR 43420). Changes: System Name: Delete entry and replace... Department of the Army Privacy Act of 1974; System of Records AGENCY: Department of the Army, DoD....

  20. 78 FR 5792 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: January 23, 2013. Aaron Siegel, Alternate OSD... Reporting System (MRRS) (May 5, 2006, 71 FR 26481). Changes: * * * * * System Location: Delete entry and replace with ``Space and Naval Warfare Systems Center New Orleans (SSC NOLA), 2251 Lakeshore Drive,...

  1. 78 FR 44931 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-25

    .... (February 20, 1996, 61 FR 6427). Dated: July 19, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison...: Space and Naval Warfare Systems Center, 53560 Hull Street, San Diego, CA 92152-5001. Categories of... disposing of records in the system: Storage: Electronic storage media. Retrievability: Data is retrieved...

  2. 77 FR 25993 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ...,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 27, 2012. Aaron Siegel, Alternate... Civilian Portfolio (HRCP). System location: Space and Naval Warfare Command, SPAWAR, 1325 10th Street SE... the system: Storage: Electronic storage media. Retrievability: Name, Social Security Number...

  3. 76 FR 51002 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: August 12, 2011. Aaron Siegel, Alternate OSD Federal... with visual dysfunction related to traumatic brain injury, with an eye injury and a visual acuity in..., outpatient visit dates, and information on where eye or traumatic brain injury occurred. Authority...

  4. 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 Brazilian Communities…

  5. 78 FR 45513 - Privacy Act of 1974; Computer Matching Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ... FR 25818. The matching agreement, as required by 5 U.S.C. 552a(r) of the Privacy Act of 1974, and an... Individuals'', dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: July 24, 2013. Aaron Siegel... Base'', November 23, 2011, 76 FR 72391. 3. HHS will be disclosing, as applicable, to DMDC personal...

  6. 76 FR 77811 - Privacy Act of 1974; Notice of a Computer Matching Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... Federal Register at 54 FR 25818 on June 19, 1989. The matching agreement, as required by 5 U.S.C. 552a(r... Records about Individuals,' dated February 8, 1996 (61 FR 6435). ] Dated: December 9, 2011. Aaron Siegel... Rehabilitation and Employment Records--VA'' (58 VA 21/22/28), published at 74 FR 29275 (June 19, 2009), and...

  7. 76 FR 50460 - Privacy Act of 1974; Notice of a Computer Matching Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... Resources'' at 61 Federal Register (FR) 6435, February 20, 1996, and OMB guidelines pertaining to computer... Federal Register at 54 FR 25818 on June 19, 1989. The matching agreement, as required by 5 U.S.C. 552a(r... Individuals,' dated February 8, 1996 (61 FR 6435). Dated: August 9, 2011. Aaron Siegel, Alternate OSD...

  8. 78 FR 35609 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: June 10, 2013. Aaron Siegel, Alternate OSD Federal... Management System (PRIMS) (August 13, 2007, 72 FR 45235). Changes: * * * * * System location: Delete entry..., abdomen, waist, hips, percent body fat), Physical Readiness Test data, Fitness Enhancement Program...

  9. 77 FR 56632 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... About Individuals,'' dated February 8, 1996, (February 20, 1996, 61 FR 6427). Dated: September 10, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. F036 AF PC A System Name: Effectiveness/Performance Reporting Records (February 10, 2009, 74 FR 6591)....

  10. 77 FR 271 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: December 29, 2011. Aaron Siegel, Alternate OSD... (December 4, 2009, 74 FR 63734). Changes: * * * * * System location(s): Delete entry and replace with... address, date and place of birth; height; weight; hair and eye color; citizenship; grade/rank;...

  11. 77 FR 32601 - Revised Non-Foreign Overseas Per Diem Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... Bulletin Number 282. This bulletin lists revisions in the per diem rates prescribed for U.S. Government... 282 is being published in the Federal Register to assure that travelers are paid per diem at the most... Civilian Bulletin 282 are updated rates for Puerto Rico. Dated: May 29, 2012. Aaron Siegel, Alternate...

  12. 78 FR 22854 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... submitted on April 1, 2013, to the House Committee on Oversight and Government Reform, the Senate Committee... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 1, 2013. Aaron Siegel... News Releases (June 24, 2011; 76 FR 37082). Changes: * * * * * System location: Delete entry...

  13. 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…

  14. 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…

  15. 76 FR 46767 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ..., 1996, 61 FR 6427). Dated: July 29, 2011. Aaron Siegel, Alternate OSD Federal Register Liaison Officer... Department of the Army Privacy Act of 1974; System of Records AGENCY: Department of the Army, DoD. ACTION: Notice to Add a System of Records. SUMMARY: The Department of the Army proposes to add a system...

  16. 76 FR 61680 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). ] Dated: September 29, 2011. Aaron... Department of the Army Privacy Act of 1974; System of Records AGENCY: Department of the Army, Department of Defense (DoD). ACTION: Notice to add a system of records. SUMMARY: The Department of the Army proposes...

  17. 78 FR 26623 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: May 2, 2013. Aaron Siegel, Alternate OSD Federal... Department of the Army Privacy Act of 1974; System of Records AGENCY: Department of the Army, DoD. ACTION: Notice to add a new System of Records. SUMMARY: The Department of the Army proposes to add a new...

  18. 78 FR 34352 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: June 3, 2013. Aaron Siegel, Alternate OSD Federal Register... clearance and current status, passport information, language capability, self-rating/level of expertise and... reference. System manager(s) and address: Training Specialist, Curriculum Department, Defense Institute...

  19. 78 FR 61345 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... Management System Office, 4800 Mark Center Drive, East Tower, 2nd Floor, Suite 02G09, Alexandria, VA 22350..., and the Office of Management and Budget (OMB) pursuant to paragraph 4c of Appendix I to OMB Circular... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: September 30, 2013. Aaron Siegel, Alternate...

  20. 77 FR 37002 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-20

    ..., 1996, 61 FR 6427). Dated: June 15, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer..., 74 FR 66298). Changes: * * * * * System location: Delete entry and replace with ``Primary location... dependents age 18 and older; DoD Civilians; DoD Contractors; other government civilians; U.S. Civilians;...

  1. 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…

  2. 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…

  3. 78 FR 34994 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ...://www.regulations.gov . Follow the instructions for submitting comments. Mail: Federal Docket Management... ineligible dependents. Affected Public: Individuals or households Annual Burden Hours: 17,474 Number of..., waste, and abuse of dependent benefits. Dated: June 4, 2013. Aaron Siegel, Alternate OSD...

  4. 76 FR 27369 - Sunshine Act Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... soon as possible to allow time to make arrangements. Dated: May 9, 2011. Aaron Bishop, Executive... DISABILITY Sunshine Act Meetings TIME AND DATES: The board meeting will be held on Thursday, May 19, 2011, 1... (202) 272-2022; or may also be e-mailed to ncd@ncd.gov at any time. PORTIONS OPEN TO THE PUBLIC:...

  5. 78 FR 50043 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-16

    .... Dated: August 13, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of... Area Air Defense Command, Control, and Intelligence (FAAD C2I) Systems, 75 AN/VRC-92E SINCGARS Radios... SENTINEL Radars, 7 AN/YSQ-184D Forward Area Air Defense Command, Control, and Intelligence (FAAD...

  6. 76 FR 35191 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ..., medical/psychological information, financial, employment, training records, test results and education... (February 20, 1996, 61 FR 6427). Dated: June 9, 2011. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. LDIA 0660 Security Files (July 24, 2006, 71 FR 41784) * * * * *...

  7. 78 FR 31528 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... (February 20, 1996, 61 FR 6427). Dated: May 7, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. Z0035-01 System Name: Financial Transaction Data (December 28, 2007, 72 FR...; and commissary patron profile information; social media (e.g. Facebook, Twitter, Flickr,...

  8. 78 FR 35610 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 10, 2013. Aaron Siegel, Alternate OSD Federal... Tracking System (April 2, 2008, 73 FR 17961) Changes: * * * * * ] Categories of records in the system... formulate response letters may contain name, Social Security Number (SSN), business or company name,...

  9. 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,…

  10. Theory Illuminates (and Conceals): A Response to the Critique by Samantha Caughlan

    ERIC Educational Resources Information Center

    Schutz, Aaron

    2005-01-01

    In a response (in this issue of "Educational Researcher," p14-16) to this author's previous essay, "Rethinking Domination and Resistance: Challenging Postmodernism" ("Educational Researcher," Jan-Feb 2004), Samantha Caughlan argues that Aaron Schutz was incorrect in his description of the workings of oppression. In this article, Schutz responds to…

  11. 77 FR 69807 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... (February 20, 1996, 61 FR 6427). Dated: November 15, 2012. Aaron Siegel, Alternate OSD Federal Register... System (DEERS), (August 3, 2011, 76 FR 46757). Changes: * * * * * System name: Delete entry and replace... may be eligible for expedited naturalization (Pub. L. 108-136, Section 1701, and E.O. 13269,...

  12. Research in Sociology of Education and Socialization. Volume 10.

    ERIC Educational Resources Information Center

    Pallas, Aaron M., Ed.

    This volume is a mixture of research reviews, theoretical syntheses, and empirical analyses addressing issues in the sociology of education. Following an introduction by Aaron M. Pallas, the book is divided into eight chapters: (1) "The Sociology of Education: Its Development in the United States" (Robert Dreeben); (2) "In Comparative Isolation:…

  13. 76 FR 52320 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-22

    ..., 1996 (February 20, 1996, 61 FR 6427). Dated: August 15, 2011. Aaron Siegel, Alternate OSD Federal... certificates of medical necessity; Medicare and Medicaid coverage data; and data on enrollment in various.... chapter 55, Medical and Dental Care; 32 CFR 199.17, TRICARE Program; 45 CFR part 160, Health and...

  14. 77 FR 40863 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-11

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: July 5, 2012. Aaron Siegel... contesting contents and appealing initial agency determinations are published in 32 CFR part 326 or may be.... 553(b)(1), (2), and (3), and published in 32 CFR part 326. For additional information contact...

  15. 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…

  16. 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).

  17. 78 FR 73507 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: December 2, 2013. Aaron Siegel, Alternate OSD... Practices Records (October 27, 2011, 76 FR 66696). Changes: System name: Delete entry and replace with... arbitrations, negotiability, and representation issues. DATES: This proposed action will be effective...

  18. 78 FR 73512 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: December 3, 2013. Aaron Siegel, Alternate OSD... Flag Officers (March 7, 2007, 72 FR 10189). Changes: * * * * * Categories of records in the system... officers for the purpose of providing briefings and outreach materials, and facilitating...

  19. 76 FR 49753 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ..., dexterity, cognitive, and/or communications impairments in the form of an accessible work environment. The..., dexterity, cognitive, and/or communications impairments in the form of an accessible work environment. The... (February 20, 1996, 61 FR 6427). Dated: August 5, 2011. Aaron Siegel, Alternate OSD Federal Register...

  20. 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…

  1. 77 FR 31591 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: May 23, 2012. Aaron Siegel... General Records (December 2, 2008, 73 FR 73252). * * * * * Categories of records in the system: Delete... Office, Office of Warfighting Integration and Chief Information officer, ATTN: SAF/CIO A6, 1800 Air...

  2. 78 FR 14282 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: February 28, 2013. Aaron Siegel... Access Management System (TEAMS) (April 29, 2004, 69 FR 23497). Changes: * * * * * Categories of records... electronic storage media.'' * * * * * Safeguards: Delete entry and replace with ``Electronic records...

  3. 77 FR 19266 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ... (February 20, 1996, 61 FR 6427). Dated: March 26, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. DWHS E03 System name: Security Review Index File (October 7, 2009, 74 FR..., personal phone numbers (home/ cell), personal/home email address, home mailing address of...

  4. 78 FR 70543 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ...://www.regulations.gov as they are received without change, including any personal identifiers or contact...,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: November 21, 2013. Aaron Siegel... requester may also visit one of the system managers listed on the WHCA intranet. As proof of identity...

  5. 78 FR 14297 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ..., 2008, 73 FR 17331). Changes: * * * * * System location: Delete entry and replace with ``Office of...://www.regulations.gov as they are received without change, including any personal identifiers or contact..., 1996 (February 20, 1996, 61 FR 6427). Dated: February 28, 2013. Aaron Siegel, Alternate OSD...

  6. 78 FR 14278 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ..., 2008; 73 FR 40304). Changes: * * * * * System name: Delete entry and replace with ``Debarment and... without change, including any personal identifiers or contact information. FOR FURTHER INFORMATION CONTACT..., 1996 (February 20, 1996, 61 FR 6427). Dated: February 28, 2013. Aaron Siegel, Alternate OSD...

  7. 78 FR 69393 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... Geospatial-Intelligence Agency Enterprise Workforce System (May 24, 2013, 78 FR 31526) Changes... on the Internet at http://www.regulations.gov as they are received without change, including any...,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: November 12, 2013. Aaron...

  8. 77 FR 56822 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ... Responsibility/Ethics File (July 30, 1999, 64 FR 41401). Changes: Delete entry and replace with ``N05800-2... Internet at http://www.regulations.gov as they are received without change, including any personal... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: September 11, 2012. Aaron...

  9. 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,…

  10. 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…

  11. International Education as an Agent of Democratization

    ERIC Educational Resources Information Center

    Comp, David

    2004-01-01

    This paper is guided by Aaron Benavot's (1999) question "What are the specific mechanisms and processes linking higher education and increasing levels of democracy in the recent period?" Benavot suggests that one research approach should focus on "students studying abroad, particularly those in North American or Western European universities,…

  12. 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 depression.…

  13. 78 FR 32635 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: May 23, 2013. Aaron Siegel... terrorism (``known or suspected terrorists''), individuals who were officially detained during military operations, but not as Enemy Prisoners of War, and who have been identified to pose an actual or...

  14. 78 FR 35607 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 10, 2013. Aaron Siegel, Alternate OSD Federal... and Tracking System (April 2, 2008, 73 FR 17959) Changes: * * * * * System location: Delete entry and... of response letter; or case file number.'' * * * * * Retention and disposal: Delete entry and...

  15. 78 FR 17384 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ...: Notice to alter a System of Records. SUMMARY: The Defense Logistics Agency proposes to alter a system of..., Defense Logistics Agency, ATTN: DGA, 8725 John J. Kingman Road, Suite 1644, Fort Belvoir, VA 22060-6221... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). ] Dated: March 18, 2013. Aaron...

  16. 77 FR 22290 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 9, 2012. Aaron Siegel... Support System (September 6, 2007, 72 FR 51215) Changes: * * * * * System name: Delete entry and replace... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Intelligence Agency,...

  17. 77 FR 39488 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... Individuals, ``dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: June 28, 2012. Aaron Siegel... Visas (October 13, 2009, 74 FR 52462). Changes: * * * * * System Location: Delete entry and replace with... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Intelligence Agency,...

  18. 77 FR 57076 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-17

    ..., 1996, 61 FR 6427). Dated: September 11, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. LDIA 0209 Litigation and Disposition Documentation (June 5, 2006, 71 FR... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Intelligence Agency,...

  19. 77 FR 21976 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: April 9, 2012. Aaron Siegel... (March 18, 2010, 75 FR 13089) Changes: * * * * * System name: Delete entry and replace with ``DIA... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Intelligence Agency,...

  20. 78 FR 5787 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ..., 1996, 61 FR 6427). Dated: January 7, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. LDIA 0450 System name: Drug-Free Workplace Files (September 9, 2009, 74 FR 46418... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Intelligence Agency,...

  1. Conversation with Copland

    ERIC Educational Resources Information Center

    Music Educators Journal, 1973

    1973-01-01

    Records a conversation between American composer Aaron Copland and Malcolm E. Besson, editor of Music Educators Journal. Mr. Copland discusses teaching, American music, and notes the greater number of composers writing today, and the livelier atmosphere of college music departments. (DS)

  2. 78 FR 17386 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... Individuals,'' dated February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: March 18, 2013. Aaron Siegel... (April 12, 2011; 76 FR 20341). Changes: * * * * * System location: Delete entry and replace with ``Public... of the Secretary Privacy Act of 1974; System of Records AGENCY: Defense Logistics Agency, DoD....

  3. 77 FR 40865 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-11

    ... 8, 1996 (February 20, 1996, 61 FR 6427). Dated: July 5, 2012. Aaron Siegel, Alternate OSD Federal..., military rank, and address; other names used, other ID number, citizenship, gender, race/ethnicity, birth... address, mother's middle name, family member information including name, relationship to sponsor,...

  4. 77 FR 29619 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... February 8, 1996 (February 20, 1996, 61 FR 6427). Dated: May 15, 2012. Aaron Siegel, Alternate OSD Federal... personnel. Categories of records in the system: Name, Social Security Number (SSN), gender, race/ethnicity... (citizenship, gender, date of birth, address, phone number, email address), medical information,...

  5. 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…

  6. 77 FR 26260 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-03

    ... available for public viewing on the Internet at http://www.regulations.gov as they are received without... (February 20, 1996, 61 FR 6427). Dated: April 30, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison... (February 3, 2010, 75 FR 5579). Changes: * * * * * System name: Add ``Enterprise'' after ``Agency''....

  7. 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.

  8. The Past, Present, and Future of Literacy Education: Comments from a Panel of Distinguished Educators, Part II.

    ERIC Educational Resources Information Center

    Aaron, Ira E.; And Others

    1990-01-01

    Presents a panel discussion of five eminent educators (Ira Aaron, Jeanne Chall, Dolores Durkin, Kenneth Goodman, and Dorothy Strickland) on a variety of issues in literacy education, including the politics of literacy education and the challenges facing literacy educators in years to come. (MG)

  9. Removal of Fe3+ and Zn2+ from plasma metalloproteins by iron chelating therapeutics depicted with SEC-ICP-AES.

    PubMed

    Sooriyaarachchi, Melani; Gailer, Jürgen

    2010-08-28

    The iron chelation therapy drugs desferrioxamine B (DFO) and deferiprone (DFP) are used to treat iron overload patients, but not much is known about their adverse effects on other essential metals in vivo. After the addition of a clinically relevant dose of DFP or an equimolar dose of DFO to human plasma in vitro, the mixtures were analyzed by size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES). Simultaneous detection of the emission lines of copper, iron and zinc allowed the visualization of changes that these drugs exerted at the metalloprotein level. After the addition of DFP, a <10 kDa novel Fe-peak was detected and identified as (DFP)(3)Fe, whereas DFO resulted in the elution of a much smaller amount of Fe in this elution range. In fact, DFP was approximately 8-times more efficient than DFO regarding the removal of Fe from plasma proteins. The addition of both iron chelators also resulted in the elution of a <10 kDa novel Zn-peak. DFP abstracted twice as much Zn from plasma proteins compared to DFO. The identification of one of these peaks as (DFP)(2)Zn establishes a feasible biomolecular basis for the etiology of Zn-deficiency in patients that undergo long-term treatment with these drugs. Our results demonstrate that the analysis of plasma by SEC-ICP-AES can simultaneously provide insight into the efficacy of chelation therapy drugs and their adverse health effects at the metalloprotein level. Thus, SEC-ICP-AES emerges as a useful analytical tool to visualize health-relevant bioinorganic chemistry-related reactions of medicinal drugs in blood plasma in vitro.

  10. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents II: the mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone.

    PubMed

    Richardson, D R; Milnes, K

    1997-04-15

    We have recently screened 36 analogues of the lipophilic iron (Fe) chelator, pyridoxal isonicotinoyl hydrazone (PIH), for their antiproliferative effect (Richardson et al, Blood 86:4295, 1995). Of these compounds, 1 chelator derived from salicylaldehyde benzoyl hydrazone (206) and 4 ligands derived from 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone (308, 309, 311, and 315) showed pronounced antiproliferative activity, being far more effective than desferrioxamine (DFO). The present study was designed to investigate in detail the mechanism of action of these PIH analogues in a variety of neoplastic cell lines. This investigation showed that the analogues were far more active than DFO at inhibiting cellular proliferation and 3H-thymidine, 3H-leucine, and 3H-uridine incorporation. Additional experiments showed that, in contrast to DFO, the 5 analogues were potent at preventing 59Fe uptake from transferrin (Tf) and increasing 59Fe release from cells at concentrations as low as 10 micromol/L. Examination of the distribution of 59Fe in neoplastic cells using native polyacrylamide gel electrophoresis (PAGE)/59Fe-autoradiography showed that most of the 59Fe taken up from Tf was incorporated into ferritin, although 3 other previously unrecognized components (bands A, B, and C) were also identified. Band C comigrated with 59Fe-citrate and was chelated on incubation of neuroblastoma cells with DFO, PIH, or the PIH analogues, with this compartment being the main intracellular target of these ligands. Further work showed that the effects of the chelators at inducing characteristics consistent with apoptosis or necrosis were cell line-specific, and while DFO increased the percentage of cells in the G0/G1 phases in all cell types, the effect of analogue 311 on the cell cycle was variable depending on the cell line. This study provides further evidence for the potential use of these Fe chelators as anticancer agents.

  11. In vitro inhibition of human cytomegalovirus replication by calcium trinatrium diethylenetriaminepentaacetic acid.

    PubMed

    Cinatl, J; Hoffmann, F; Cinatl, J; Weber, B; Scholz, M; Rabenau, H; Stieneker, F; Kabickova, H; Blasko, M; Doerr, H W

    1996-06-01

    Desferrioxamine (DFO) has been shown to inhibit human cytomegalovirus (CMV) replication in vitro. In the present study, we compared antiviral effects of DFO in human foreskin fibroblast (HFF) cells against several CMV strains with those of other chelators that interact with iron and other ions from different pools. DFO, a hydrophilic chelator, that may chelate both intracellular and extracellular ions inhibited production of CMV late antigen at 50% effective concentrations (EC50S) ranging from 6.2 to 8.9 microM. EC50S for calcium trinatrium diethylenetriaminepentaacetic acid (CaDTPA) ranged from 6.1 to 9.9 microM. EC50S for 2,2'-bipyridine (BPD), a hydrophobic chelator, which diffuses into cell membranes ranged from 65 to 72 microM. Concentrations which inhibited BrdU incorporation into cellular DNA by 50% (IC50S) ranged from 8.2 to 12.0 microM (DFO), from 65 to 89 microM (BPD), and from 139 to 249 microM (CaDTPA). CaDTPA was the only chelator which completely inhibited production of infectious virus in HFF and vascular endothelial cells at concentrations which had no significant effects on cellular DNA synthesis and growth. Addition of stoichiometric amounts of Fe3+ in the culture medium of HFF cells completely eliminated antiviral effects of DFO while antiviral effects of CaDTPA and BPD were only moderately affected. Fe2+ and Cu2+ were stronger inhibitors of CaDTPA than Fe3+; however, Mn2+ and Zn2+ completely suppressed antiviral effects of CaDTPA. The results show that CaDTPA is a novel nontoxic inhibitor of CMV replication. The antiviral activity of CaDTPA is suppressed by metal ions with a decreasing potency order of Mn2+/Zn2+ > Fe2+ > Cu2+ > Fe3+.

  12. 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.

  13. 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

  14. Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET

    NASA Astrophysics Data System (ADS)

    Miller, Larissa; Winter, Gordon; Baur, Benjamin; Witulla, Barbara; Solbach, Christoph; Reske, Sven; Lindén, Mika

    2014-04-01

    Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have recently attracted a lot of interest as both imaging agents and carriers for drugs in vitro and in vivo. Here we present results related to the synthesis of PET imageable MSNs carrying the long-lived 89Zr isotope (half-life of 78.4 hours). Here, 89Zr4+ was immobilized through covalent attachment of the complexing agent p-isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the presence of the high DFO content on the MSNs, quantitative 89Zr4+ labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed 89Zr4+. The stability of the 89Zr-labeled MSNs against leaching of 89Zr4+ was verified for 24 hours. The high signal strength of the 89Zr-DFO-MSNs was evidenced by successful PET imaging using a mouse model at particle loadings one order of magnitude lower than those previously applied in PET-MSN studies. The biodistribution followed the same trends as previously observed for MSNs of different sizes and surface functionalities. Taken together, our results suggest that 89Zr-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have

  15. Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas

    PubMed Central

    Oteo, M.; Romero, E.; Cámara, J. A.; de Martino, A.; Arroyo, A. G.; Morcillo, M. Á.; Squatrito, M.; Martinez-Torrecuadrada, J. L.; Mulero, F.

    2016-01-01

    Background A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models. Methods An anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments. Results 89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models. Conclusion A new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In

  16. Pharmacological Suppression of CNS Scarring by Deferoxamine Reduces Lesion Volume and Increases Regeneration in an In Vitro Model for Astroglial-Fibrotic Scarring and in Rat Spinal Cord Injury In Vivo

    PubMed Central

    Krafft, Stefanie; Estrada, Veronica; Brazda, Nicole; Ziegler, Brigida; Faissner, Andreas; Müller, Hans Werner

    2015-01-01

    Lesion-induced scarring is a major impediment for regeneration of injured axons in the central nervous system (CNS). The collagen-rich glial-fibrous scar contains numerous axon growth inhibitory factors forming a regeneration-barrier for axons. We demonstrated previously that the combination of the iron chelator 2,2’-bipyridine-5,5’-decarboxylic acid (BPY-DCA) and 8-Br-cyclic AMP (cAMP) inhibits scar formation and collagen deposition, leading to enhanced axon regeneration and partial functional recovery after spinal cord injury. While BPY-DCA is not a clinical drug, the clinically approved iron chelator deferoxamine mesylate (DFO) may be a suitable alternative for anti-scarring treatment (AST). In order to prove the scar-suppressing efficacy of DFO we modified a recently published in vitro model for CNS scarring. The model comprises a co-culture system of cerebral astrocytes and meningeal fibroblasts, which form scar-like clusters when stimulated with transforming growth factor-β (TGF-β). We studied the mechanisms of TGF-β-induced CNS scarring and compared the efficiency of different putative pharmacological scar-reducing treatments, including BPY-DCA, DFO and cAMP as well as combinations thereof. We observed modulation of TGF-β-induced scarring at the level of fibroblast proliferation and contraction as well as specific changes in the expression of extracellular matrix molecules and axon growth inhibitory proteins. The individual and combinatorial pharmacological treatments had distinct effects on the cellular and molecular aspects of in vitro scarring. DFO could be identified as a putative anti-scarring treatment for CNS trauma. We subsequently validated this by local application of DFO to a dorsal hemisection in the rat thoracic spinal cord. DFO treatment led to significant reduction of scarring, slightly increased regeneration of corticospinal tract as well as ascending CGRP-positive axons and moderately improved locomotion. We conclude that the in

  17. Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease.

    PubMed

    Percy, Maire E; Kruck, Theo P A; Pogue, Aileen I; Lukiw, Walter J

    2011-11-01

    In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD.

  18. Latent Fingerprint Development on Thermal Paper Using Traditional Ninhydrin and 1,2-indanedione.

    PubMed

    Chen, Chun-Chieh; Yu, Yung-Chien; Lee, Henry C; Giang, Yun-Seng; Wang, Sheng-Meng

    2016-01-01

    Thermal paper poses a significant challenge to latent print development as it tends to change color when traditional fingerprint development formulations are applied to it. In this study, the optimal components of ninhydrin, 1,2-indanedione, 1,8-diazafluoren-9-one (DFO), and 5-methylthioninhydrin (5-MTN) for yielding clear fingerprints on thermal paper were determined by systematically adjusting the relative amounts of the reagents, polar solvents, and the nonpolar diluent petroleum ether, followed by validation on text-printed thermal paper. Specifically, 3.0% ethyl acetate as the polar solvent in petroleum ether was found to be the optimal combination; the optimal dilution ratios of ninhydrin, DFO, and 5-MTN original solutions with petroleum ether were 1 to 2, 11, and 7, respectively. The optimal concentration of 1,2-indanedione in petroleum ether was 0.125 g/L, with a string of 0.5% ethyl acetate in petroleum ether. PMID:26248596

  19. 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)

  20. Iron release and oxidant damage in human myoblasts by divicine.

    PubMed

    Ninfali, P; Perini, M P; Bresolin, N; Aluigi, G; Cambiaggi, C; Ferrali, M; Pompella, A

    2000-01-01

    Divicine is an aglycone derived from vicine, a glucosidic compound contained in fava beans (Vicia faba major or broad beans). In this study, we investigated the effect of divicine on cultured human myoblasts from normal subjects, in order to see if the drug may induce signs of oxidant stress in these cells. Myoblasts incubated 24 hours in the presence of 1 mM divicine, showed an increase of carbonyl groups and 4-hydroxynonenal (4-HNE) bound to cell proteins, as well as a significant release of iron and lactate dehydrogenase in the culture medium. Desferrioxamine (DFO), an iron chelator, significantly prevented protein oxidation and formation 4-HNE adducts. Our results can be interpreted as indicating that divicine autooxidizes both at extracellular level and into myoblasts thus inducing the release of free iron, which initiates oxidation of cellular proteins and lipids. DFO protects the cells by subtracting the free iron both at intracellular and extracellular level. PMID:10794072

  1. 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.

  2. Aluminium-related osteodystrophy and desferrioxamine treatment: role of phosphorus.

    PubMed

    Jorgetti, V; Soeiro, N M; Mendes, V; Pereira, R C; Crivellari, M E; Coutris, G; Borelli, A; Leite, M O; Nussenzweig, I; Marcondes, M

    1994-01-01

    We investigated (1) the prevalence of aluminium overload among 96 patients with symptomatic bone disease haemodialysed from 1987 to 1989 in the Sao Paulo area, Brazil; (2) the effect of 6 months desferrioxamine (DFO) treatment (1-2g/week). All patients underwent a first bone biopsy. Aluminium overload (extent of stainable bone aluminium more than 20% trabecular surface) was observed in 74 of 96 patients. Forty overloaded patients were divided into patients with high bone formation rate (BFR) (group 1; n = 17) and patients with low BFR (group 2; n = 23), and had a second biopsy after DFO therapy. In both groups aluminium surface was reduced after treatment (P < 0.001), osteoblast surface (P < 0.02-P < 0.01) and plasma parathyroid hormone (iPTH) (P < 0.01) increased. In group 1 BFR remained high. In group 2 BFR remained low in 16 patients (2a) and increased in seven (P < 0.02) (2b). In group 2a plasma phosphorus was below that in group 2b patients, before (P < 0.03) and after (P < 0.01) DFO. The histological features of group 2a patients resembled hypophosphataemic osteomalacia, those of group 2b patients aluminium osteodystrophy. These data show a high prevalence of aluminium overload in Brazilian patients. Low-dose DFO therapy was safe, decreased bone pain, prevented fractures, and reduced stainable bone aluminium. Bone lesions only partially improved, suggesting that low phosphorus intake and/or plasma calcitriol concentrations may have prevented improvement of bone formation and mineralization.

  3. 76 FR 68439 - Meeting of the Small Communities Advisory Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ..., 2011, at 3 p.m. to 4:30 p.m. (E.T.) at the U.S. EPA East Building, 1201 Constitution Avenue NW... to attend. The Subcommittee will hear comments from the public between 3:30 p.m. and 4 p.m. (E.T.) on....frances@epa.gov or contact Frances Eargle the Designated Federal Officer (DFO) at the number listed...

  4. 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.

  5. 76 FR 37121 - Medicare Program; Second Semi-Annual Meeting of the Advisory Panel on Ambulatory Payment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Boulevard, Baltimore, Maryland 21244-1850. FOR FURTHER INFORMATION CONTACT: Paula Smith, Designated Federal Officer (DFO), CMS, CMM, HAPG, DOC, 7500 Security Boulevard, Mail Stop C4-05-17, Baltimore, MD 21244-1850..., Sc.D., F.A.C.H.E.* David Halsey, M.D. Brian D. Kavanagh, M.D., M.P.H. Judith T. Kelly, B.S.H.A.,...

  6. 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. PMID:19527781

  7. 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

  8. Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases

    PubMed Central

    Tsai, Shih-Hung; Huang, Po-Hsun; Hsu, Yu-Juei; Peng, Yi-Jen; Lee, Chien-Hsing; Wang, Jen-Chun; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1α and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1α can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1α inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1α is pivotal for the development of AAA. Our study provides a rationale for using HIF-1α inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. PMID:27363580

  9. Intermediate-term evaluation of a pratical chelation protocol based on stratification of thalassemic patients by serum ferritin and magnetic resonance imaging cardiac t2*.

    PubMed

    Ha, Shau-Yin; Mok, Amanda Sio-Peng; Chu, Winnie Chiu-Wing; Rasalkar, Darshana Dattatray; Cheuk, Daniel Ka-Leung; Chiang, Alan Kwok-Shing; Ho, Marco Hok-Kung; Chan, Godfrey Chi-Fung

    2011-01-01

    A standardized chelation protocol was applied by stratifying transfusion-dependent thalassemic patients into three groups, namely well chelated group (A), inadequately chelated group without (B) or with (C) risk of cardiac complications based on serum ferritin (SF) levels and magnetic resonance imaging (MRI) cardiac T2* measurements. Group A patients were advised to continue with deferoxamine (DFO) (Regimen Ic). Group B patients were given options of either intensification of DFO alone (Regimen Ii), deferiprone (L1) alone (Regimen II) or combined therapy with L1 and DFO (Regimen III). Group C patients were advised to take either Regimen Ii or Regimen III. The 1-year result showed that the combined therapy (Regimen III) significantly reduced SF level, cardiac and liver iron in the groups of inadequately chelated patients. The same set of outcome parameters was repeated at 2.5 years of treatment so as to evaluate the intermediate-term effects of this risk stratified chelation protocol. The number of patients with cardiac T2* <20 ms decreased from 34 (60%) at baseline to 17 (30%) of the whole cohort of 57 patients at the end of the study. There were further improvements in SF, cardiac and liver T2* in Group C patients. Significant improvement in left ventricular ejection fraction (LVEF) was demonstrated after 2.5 years of the combined therapy group in which the change was not initially apparent after the first year of assessment.

  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. Iron depletion results in Src kinase inhibition with associated cell cycle arrest in neuroblastoma cells

    PubMed Central

    Siriwardana, Gamini; Seligman, Paul A

    2015-01-01

    Iron is required for cellular proliferation. Recently, using systematic time studies of neuroblastoma cell growth, we better defined the G1 arrest caused by iron chelation to a point in mid-G1, where cyclin E protein is present, but the cyclin E/CDK2 complex kinase activity is inhibited. In this study, we again used the neuroblastoma SKNSH cells lines to pinpoint the mechanism responsible for this G1 block. Initial studies showed in the presence of DFO, these cells have high levels of p27 and after reversal of iron chelation p27 is degraded allowing for CDK2 kinase activity. The initial activation of CDK2 kinase allows cells to exit G1 and enter S phase. Furthermore, we found that inhibition of p27 degradation by DFO is directly associated with inhibition of Src kinase activity measured by lack of phosphorylation of Src at the 416 residue. Activation of Src kinase occurs very early after reversal from the DFO G1 block and is temporally associated with initiation of cellular proliferation associated with entry into S phase. For the first time therefore we show that iron chelation inhibits Src kinase activity and this activity is a requirement for cellular proliferation. PMID:25825542

  12. Iron depletion results in Src kinase inhibition with associated cell cycle arrest in neuroblastoma cells.

    PubMed

    Siriwardana, Gamini; Seligman, Paul A

    2015-03-01

    Iron is required for cellular proliferation. Recently, using systematic time studies of neuroblastoma cell growth, we better defined the G1 arrest caused by iron chelation to a point in mid-G1, where cyclin E protein is present, but the cyclin E/CDK2 complex kinase activity is inhibited. In this study, we again used the neuroblastoma SKNSH cells lines to pinpoint the mechanism responsible for this G1 block. Initial studies showed in the presence of DFO, these cells have high levels of p27 and after reversal of iron chelation p27 is degraded allowing for CDK2 kinase activity. The initial activation of CDK2 kinase allows cells to exit G1 and enter S phase. Furthermore, we found that inhibition of p27 degradation by DFO is directly associated with inhibition of Src kinase activity measured by lack of phosphorylation of Src at the 416 residue. Activation of Src kinase occurs very early after reversal from the DFO G1 block and is temporally associated with initiation of cellular proliferation associated with entry into S phase. For the first time therefore we show that iron chelation inhibits Src kinase activity and this activity is a requirement for cellular proliferation.

  13. 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

  14. 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.

  15. Storage iron exchange in the rat as affected by deferoxamine

    SciTech Connect

    Kim, B.K.; Huebers, H.; Pippard, M.J.; Finch, C.A.

    1985-04-01

    The initial tissue localization and redistribution of radioactive iron injected intravenously into the rat as ferritin, chondroitin sulfate, and nonviable red cells was determined. Ferritin iron, initially localized in the hepatocyte, showed minimal redistribution over 24 hours in the normal animal. This may be compared with the active release of iron from the reticuloendothelial cell after the intravenous injection of nonviable red cells and chondroitin sulfate iron. All forms of iron were actively mobilized in iron-deficient animals. The effect of chelation of iron by deferoxamine (DFO) on the redistribution pattern over 4 to 6 hours was determined in iron-deficient, normal, iron-loaded, and phenylhydrazine-treated rats to evaluate the effect of iron stores and erythropoiesis. Use of DFO resulted in extensive chelation of radioactive iron within the hepatocyte and greatly reduced the amount of hepatocyte iron available for erythropoiesis. Very little chelation of reticuloendothelial cell-processed iron occurred, and there was little decrease in its utilization for red cell production. Total urinary chelate iron was independent of erythropoiesis but varied in parallel with the iron load of the animal. These studies suggest that DFO does not act on the reticuloendothelial cell but does have at least two sites of action, both of which relate to total storage iron. One involves hepatocyte stores with excretion into the intestinal tract. The other, possibly located at the hepatocyte membrane, results in urinary iron excretion.

  16. Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases.

    PubMed

    Tsai, Shih-Hung; Huang, Po-Hsun; Hsu, Yu-Juei; Peng, Yi-Jen; Lee, Chien-Hsing; Wang, Jen-Chun; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1α and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1α can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1α inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1α is pivotal for the development of AAA. Our study provides a rationale for using HIF-1α inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. PMID:27363580

  17. 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

  18. Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma.

    PubMed

    Srichairatanakool, S; Thephinlap, C; Phisalaphong, C; Porter, J B; Fucharoen, S

    2007-09-01

    Non-transferrin-bound iron (NTBI) is detectable in plasma of beta-thalassemia patients with transfusional iron overload. This form of iron may cause oxidative tissue damage and increased iron uptake, into several vital organs. Removal of NTBI species is incomplete and transient using standard intermittent desferrioxamine (DFO) or deferiprone (DFP) monotherapy. Combinations of these or other chelators may improve the protection time from NTBI and increase removal of harmful NTBI species. Curcuminoids from Curcuma longa L. is a naturally occurring phytochemical which shows a wide range of pharmacological properties including anti-oxidative, anti-inflammatory, anti-cancer and iron-chelating activities. In this study, the curcuminoids was investigated for NTBI chelation in thalassemic plasma in vitro and for the potential to improve NTBI removal when used with other chelators. Curcumin bound Fe(3+) to form a Fe(3+)-curcumin complex with a predominant absorption at 500 nm. The chemical binding of curcumin was dose- and time-dependent and more specific for Fe(3+) than Fe(2+). Using a HPLC-based NTBI assay without an aluminium blocking step, curcumin shuttled the iron from Fe(3+)-NTA complex, giving underestimated NTBI values. At equivalent concentrations DFO, DFP and curcumin decreased plasma NTBI with the order of DFP>DFO>curcumin. None of these chelators removed NTBI completely, but curcumin appeared to increase the rate of NTBI removal when added to DFP. It is proposed that the beta-diketo moiety of curcumin participates in the NTBI chelation.

  19. 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. PMID:23329319

  20. Novel Bifunctional Cyclic Chelator for (89)Zr Labeling-Radiolabeling and Targeting Properties of RGD Conjugates.

    PubMed

    Zhai, Chuangyan; Summer, Dominik; Rangger, Christine; Franssen, Gerben M; Laverman, Peter; Haas, Hubertus; Petrik, Milos; Haubner, Roland; Decristoforo, Clemens

    2015-06-01

    Within the last years (89)Zr 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 (89)Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [(89)Zr]FSC-RGD conjugates or [(89)Zr]triacetylfusarinine C (TAFC). Quantitative (89)Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [(89)Zr]DFO, [(89)Zr]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 [(89)Zr]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 (89)Zr-based PET imaging agents.

  1. 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

  2. Why there was a useful plausible analogy between geodesic domes and spherical viruses.

    PubMed

    Morgan, Gregory J

    2006-01-01

    In 1962, Donald Caspar and Aaron Klug published their classic theory of virus structure. They developed their theory with an explicit analogy between spherical viruses and Buckminster Fuller's geodesic domes. In this paper, I use the spherical virus-geodesic dome case to develop an account of analogy and deductive analogical inference based on the notion of an isomorphism. I also consider under what conditions there is a good reason to claim an experimentally untested analogy is plausible. PMID:17702504

  3. 75 FR 41483 - Environmental Impacts Statements; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ...-575-6060. Revision to FR Notice Published 04/16/2010: Extending Comment Period from 7/15/2010 to 8/30... to FR Notice Published 05/07/2010: Extending Comment Period from 6/21/2010 to 12/17/2010. EIS No.../09/2010, Contact: Aaron Snyder, 651-290-5489. Revision to FR Notice Published 06/11/2010:...

  4. Historical review: viruses, crystals and geodesic domes.

    PubMed

    Morgan, Gregory J

    2003-02-01

    In the mid 1950s, Francis Crick and James Watson attempted to explain the structure of spherical viruses. They hypothesized that spherical viruses consist of 60 identical equivalently situated subunits. Such an arrangement has icosahedral symmetry. Subsequent biophysical and electron micrographic data suggested that many viruses had >60 subunits. Drawing inspiration from architecture, Donald Caspar and Aaron Klug discovered a solution to the problem - they proposed that spherical viruses were structured like miniature geodesic domes.

  5. 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.

  6. Spin observables in the NN --> NΔ transition

    NASA Astrophysics Data System (ADS)

    Auger, J. P.; Lazard, C.; Lombard, R. J.; Silbar, R. R.

    1985-09-01

    The 16 independent amplitudes making up the NN → NΔ scattering matrix are written in forms suitable for calculating observables, particularly, spin observables. Some of these observables are calculated, using amplitudes of the unitary Aaron-Amado-Young three-body model with iterated pion-exchange forces and displayed as functions of the production angle, the incident energy and the invariant mass of Δ. Comparisons with simpler models are also given.

  7. JSC Officials in MCC Bldg 30 monitor STS-26 Discovery, OV-103, activity

    NASA Technical Reports Server (NTRS)

    1988-01-01

    JSC Officials, laughing, listen to crewmembers' commentary onboard Discovery, Orbiter Vehicle (OV) 103, during STS-26. In the Flight Control Room (FCR) of JSC's Mission Control Center (MCC) Bldg 30 and seated at the Mission Operations Directorate (MOD) console, MOD Director Eugene F. Kranz (foreground), wearing red, white and blue vest, smiles along with JSC Director Aaron Cohen and Flight Crew Operations Deputy Director Henry W. Hartsfield, Jr. (far right).

  8. 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…

  9. Intergenerational redistribution in a small open economy with endogenous fertility.

    PubMed

    Kolmar, M

    1997-08-01

    The literature comparing fully funded (FF) and pay-as-you-go (PAYG) financed public pension systems in small, open economies stresses the importance of the Aaron condition as an empirical measure to decide which system can be expected to lead to a higher long-run welfare. A country with a PAYG system has a higher level of utility than a country with a FF system if the growth rate of total wage income exceeds the interest rate. Endogenizing population growth makes one determinant of the growth rate of wage incomes endogenous. The author demonstrates why the Aaron condition ceases to be a good indicator in this case. For PAYG-financed pension systems, claims can be calculated according to individual contributions or the number of children in a family. Analysis determined that for both structural determinants there is no interior solution of the problem of intergenerational utility maximization. Pure systems are therefore always welfare maximizing. Moreover, children-related pension claims induce a fiscal externality which tends to be positive. The determination of the optimal contribution rate shows that the Aaron condition is generally a misleading indicator for the comparison of FF and PAYG-financed pension systems.

  10. comparison of effects of different long-term iron-chelation regimens on myocardial and hepatic iron concentrations assessed with T2* magnetic resonance imaging in patients with beta-thalassemia major.

    PubMed

    Perifanis, Vassilios; Christoforidis, Athanasios; Vlachaki, Efthimia; Tsatra, Ioanna; Spanos, George; Athanassiou-Metaxa, Miranda

    2007-12-01

    The aim of this study was to compare the effect of different long-term chelation regimens on heart and liver iron stores with the use of T2* magnetic resonance imaging (MRI) in patients with transfusion-dependent beta-thalassemia major. Sixty-four patients (28 men, 36 women; mean age, 26.49 +/- 5.8 years) were enrolled in the study. The 3 groups were based on the chelation therapy received. The first group (19 patients) received deferiprone (DFP) (75 mg/kg per day orally), the second group (23 patients) received deferoxamine (DFO) (30-50 mg/kg per day subcutaneously at least 5 times/week), and the third group (22 patients) received a combination of DFO (30-50 mg/kg per day, 2-3 days/week) and DFP (75 mg/kg per day, 7 days/week). MRI scans were acquired with an imager equipped with a 1.5 T magnet, and the data included myocardial and hepatic iron measurements obtained by means of T2*, and ventricular volumes and ejection fractions obtained with standard cardiovascular MRI techniques. The results revealed that the DFP and the combined groups had significantly less myocardial iron than the DFO group (mean myocardial T2*, 35.77 +/- 18.3 milliseconds and 38.05 +/- 15.3 milliseconds versus 23.77 +/- 13 milliseconds [P = .02, and P = .001], respectively). On the contrary, the DFP group had a significantly higher hepatic iron content than the DFO and combined groups (mean hepatic T2*, 3.29 +/- 2.5 milliseconds versus 8.16 +/- 8.4 milliseconds and 11.3 +/- 10.9 milliseconds [P = .014, and P = .003], respectively). No correlation was observed between myocardial T2* and hepatic T2* values (r = -0.043; P = .37). Myocardial T2* values were inversely correlated with age (r = -0.249; P = .024) and positively correlated with both left and right ventricular ejection fractions (r = 0.33 [P = .004], and r = 0.279 [P = .014], respectively). Finally, liver T2* was strongly and inversely correlated with serum ferritin concentration (r = -0.465; P = .001). In conclusion, combined

  11. 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.

  12. 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

  13. Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine

    PubMed Central

    Hassan, Mohamed Abdel Malik; Tolba, Omar Atef

    2016-01-01

    Introduction Iron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major. Methods This prospective randomized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015. Their ages were ≥ 6 years, and they had serum ferritin above 1500 μg/L and were on irregular DFO therapy. Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session. They were randomized to receive DFX (single oral daily dose of 20–40 mg/kg/day) or DFO (20–50 mg/kg/day via subcutaneous infusion over 8–10 hours, 5 days a week). Iron overload was determined by serum ferritin level. The primary endpoint was decrease of serum ferritin level below 1500 μg/L. The secondary endpoint was drug safety. Results Both drugs significantly reduced serum ferritin (p < 0.001). At the end of follow-up, there were no significant differences between the two groups in serum ferritin levels (p = 0.673) and in percent reduction of ferritin (p = 0.315). There were no significant differences between the two groups in the total amount of blood transfusion (p = 0.166) and average iron intake (p = 0.227). There were no mortalities or any serious adverse effects, neutropenia, arthropathy, or pulmonary toxicity. Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO (p = 0.254 and 0.095, respectively). Conclusion With appropriate dosing and compliance with drugs, both DFX and DFO are generally well tolerated, safe, and effective in reducing serum ferritin levels in iron-overloaded, regularly-transfused thalassemia major patients. Therefore, oral DFX is recommended for more convenience and adherence to the treatment regimen. PMID:27382454

  14. Standardized methods for the production of high specific-activity zirconium-89.

    PubMed

    Holland, Jason P; Sheh, Yiauchung; Lewis, Jason S

    2009-10-01

    Zirconium-89 is an attractive metallo-radionuclide for use in immuno-PET due to favorable decay characteristics. Standardized methods for the routine production and isolation of high-purity and high-specific-activity (89)Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52+/-0.11 mCi/muA.h at a proton beam energy of 15 MeV and current of 15 muA using a solid, commercially available (89)Y-foil target (0.1 mm, 100% natural abundance). (89)Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [(89)Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of (89)Zr was found to be in the range 5.28-13.43 mCi/microg (470-1195 Ci/mmol) of zirconium. New methods for the facile production of [(89)Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min at room temperature, and in vitro stability measurements confirmed that [(89)Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal positron emission tomography (PET) imaging studies have demonstrated that free (89)Zr(IV) ions administered as [(89)Zr]Zr-chloride accumulate in the liver, whilst [(89)Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immuno-PET imaging of (89)Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of (89)Zr in both basic science and clinical investigations.

  15. 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

    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.

  16. Uses and limitations of serum ferritin, magnetic resonance imaging T2 and T2* in the diagnosis of iron overload and in the ferrikinetics of normalization of the iron stores in thalassemia using the International Committee on Chelation deferiprone/deferoxamine combination protocol.

    PubMed

    Kolnagou, Anita; Yazman, Dilek; Economides, Charalambos; Eracleous, Eleni; Kontoghiorghes, George J

    2009-01-01

    Excess cardiac iron deposition leads to congestive cardiac failure and accounts for more than 70% of deaths in thalassemia major patients. In three separate studies involving 145 thalassemia patients, serum ferritin and magnetic resonance imaging (MRI) relaxation times T2 and T2* have been compared for assessing iron load levels during chelation treatment. In two studies, variable levels of cardiac iron load have been detected by T2 and T2* in patients treated with deferoxamine (DFO), which, however, were unrelated to serum ferritin. In most cases, similar range levels from normal to severe cardiac iron load could be identified by both the T2 and T2* methods. However, in a few cases there were substantial differences in the levels detected between the two methods. In the third study, the ferrikinetics of the normalization of the iron stores during the International Committee on Chelation (ICOC) deferiprone (L1)/DFO combination protocol was followed up using T2 and T2* and serum ferritin. Iron deposits were found not to be proportionally distributed between the liver and the heart or uniformly distributed within each organ. Iron mobilization in each patient varied and iron deposits in each organ were cleared at different rates. Despite some limitations, the application of the MRI relaxation times T2 and T2* offers the best diagnostic methods for iron overload estimations in most organs and especially the heart. These MRI methods and serum ferritin could also be used for the ferrikinetics of iron mobilization and removal during chelation therapy and the normalization of the iron stores during the ICOC L1/DFO combination protocol. There is a need to standardize the two MRI relaxation times T2 and T2* methods and identify the factors causing the differences between them.

  17. 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

  18. Combined chelation therapy with deferasirox and deferoxamine in thalassemia.

    PubMed

    Lal, Ashutosh; Porter, John; Sweeters, Nancy; Ng, Vivian; Evans, Patricia; Neumayr, Lynne; Kurio, Gregory; Harmatz, Paul; Vichinsky, Elliott

    2013-02-01

    Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9-38.2mg/g) to 12.0mg/g (range 0.96-26.7 mg/g, p<0.001). Median ferritin decreased by 24% from 2465 ng/mL (range 1110-10,700 ng/mL) to 1875 ng/mL (range 421-5800 ng/mL, p=0.002). All 6 subjects with elevated myocardial iron showed improvement in MRI T2* (p=0.031). The mean±S.E. plasma non-transferrin-bound iron (NTBI) declined from 3.10±0.25μM to 2.15±0.29μM (p=0.028). The administration of DFX during infusion of DFO further lowered NTBI (-0.28±0.08 μM, p=0.004) and labile plasma iron (LPI, -0.03±0.01 μM, p=0.006). The simultaneous administration of DFO and DFX rapidly reduced systemic and myocardial iron, and provided an excellent control of the toxic labile plasma iron species without an increase in toxicity.

  19. Lazaroid compounds prevent early but not late stages of oxidant-induced cell injury: potential explanation for the lack of efficacy of lazaroids in clinical trials.

    PubMed

    Huang, H; Patel, P B; Salahudeen, A K

    2001-01-01

    Earlier in vitro studies demonstrated the remarkable potency of the lazaroid compounds to prevent oxidant-induced early cell injury. However, the ability of lazaroid compounds to limit oxidative injury in vivo(including renal ischemia-reperfusion) has been less certain, and the early clinical trials using lazaroids to limit CNS injury or organ injury in the setting of transplantation have not been promising. Lazaroid compounds are potent inhibitors of lipid peroxidation, and their inability to influence other key injury processes, particularly during the late stages of cell injury, might partly explain the limited clinical efficacy. To test this, renal tubular (LLC-PK1) cells were incubated with 250 micromH(2)O(2)for 135 min, in the presence or absence of 2-methyl aminochroman (2-MAC, U-83836E), a lazaroid with potent ability to inhibit lipid peroxidation, or desferrioxamine, (DFO) an iron chelator with broader antioxidant efficacy. Cell injury, lipid peroxidation, DNA damage and ATP depletion were measured in the early (immediately after H(2)O(2)incubation) and late (24 h after H(2)O(2)incubation) stages of cell injury. In the early stage, 2-MAC suppressed H(2)O(2)-induced lipid peroxidation and LDH release, but not the DNA damage, ATP depletion or loss of cell replication. In contrast, DFO suppressed all of the measurements. In the late stages, despite continued suppression of lipid peroxidation, only DFO maintained significant cytoprotection against H(2)O(2), and this was accompanied by reduced DNA damage, higher ATP levels and preservation of cell proliferation. Thus, the inability of the lazaroid compound 2-MAC to sustain cytoprotection in the later stages of cell injury might provide at least a partial explanation for the inefficiency of lazaroids to limit tissue injury in clinical and certain in vivo settings. PMID:11207066

  20. 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.

  1. 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, M.P.

    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 pK{sub a}s 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, pK{sub a} = 5.94, log{beta}{sub 120} = 10.92; acetohydroxamic acid, pK{sub a} = 9.34, log{beta}{sub l20} = 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 log{beta}{sub 110} = 41.7. The solubility limited speciation of {sup 242}Pu 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.

  2. Clinical monitoring and management of complications related to chelation therapy in patients with β-thalassemia.

    PubMed

    Saliba, Antoine N; El Rassi, Fuad; Taher, Ali T

    2016-01-01

    Iron chelating agents - deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX) - are used to treat chronic iron overload in patients with β-thalassemia in an attempt to reduce morbidity and mortality related to siderosis. Each of the approved iron chelating agents has its own advantages over the others and also has its own risks, whether related to over-chelation or not. In this review, we briefly discuss the methods to monitor the efficacy of iron chelation therapy (ICT) and the evidence behind the use of each iron chelating agent. We also portray the risks and complications associated with each iron chelating agent and recommend strategies to manage adverse events.

  3. Self-assembled monolayers for studying enzyme immobilization and ion recognition

    NASA Astrophysics Data System (ADS)

    Kang, Jie

    This thesis explores the use of self-assembled monolayers on gold for studying enzyme immobilization and ion recognition. Chapter 1 serves as a general introduction to biosensing, self-assembled monolayers, protein immobilization, and surface characterization techniques. Chapter 2 through Chapter 5 describe the immobilization of a redox enzyme, glucose oxidase, to a variety of functional self-assembled monolayers by either noncovalent adsorption or covalent attachment. The characteristics of different immobilization methods are investigated, and the activity of the immobilized enzyme is assessed electrochemically. Chapter 2 presents detailed procedures for measuring glucose oxidase activity by an electrochemical technique---cyclic voltammetry. Chapter 3 describes the adsorption of glucose oxidase to hydrophobic and hydrophilic self-assembled monolayers (SAMs). Significant glucose oxidase adsorption to hydrophobic, methyl-terminated SAMs was observed, while long chain, hydrophilic SAMs terminated by hydroxyl and carboxyl groups resist enzyme adsorption. Chapter 4 examines the covalent attachment of glucose oxidase to N-hydroxysuccinimide ester (NHS ester)-terminated self-assembled monolayers. The reactivity of the surface NHS ester group is found to increase as its coverage is lowered. This observation is explained by the steric effect. Chapter 5 reports the electrostatic adsorption of glucose oxidase to self-assembled monolayers of cystamine. The adsorbed enzyme shows superior activity to enzyme immobilized by other means. The rate constants of surface enzyme catalysis are determined and compared with those of the enzyme in solution. Chapter 6 is concerned with iron (III) recognition by a self-assembled monolayer terminated with a siderophore group, desferrioxamine (H3DFO). We first demonstrate that the iron coverage of the ferrioxamine (FeDFO)-terminated SAM can be successfully assayed by cyclic voltammetry. We then present results for iron (III) binding to the H3

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats

    SciTech Connect

    Shah, S.V. )

    1988-03-01

    The authors examined the effect of scavengers of reactive oxygen metabolites on proteinuria in the passive Heymann nephritis model of membranous nephropathy. Passive Heymann nephritis was induced by a single intravenous injection of anti-Fx1A IgG in a dose of 10 mg/100 g body weight. Superoxide dismutase, a scavenger of superoxide or catalase which destroys hydrogen peroxide, did not affect the proteinuria. In contrasts, dimethylthiourea (DMTU), a scavenger of hydroxyl radical, markedly reduced the proteinuria. Experiments with {sup 125}I-labeled anti-Fx1A antibody demonstrated that DMTU did not affect the amount of antibody deposited in the kidney. Semiquantitative estimation of IgG and complement deposition in the kidneys showed no differences between the DMTU-treated and control rats. A second hydroxyl radical scavenger, sodium benzoate also resulted in marked reduction in proteinuria. Because of the participation of iron in biological systems to generate hydroxyl radical, they also examined the effect of deferoxamine (DFO) an iron chelator, on the anti-Fx1A-induced proteinuria. There was a significant reduction in proteinuria in rats treated concurrently with DFO. These results suggest a potential role of the hydroxyl radical in passive Heymann nephritis.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin

    PubMed Central

    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. PMID:27057276

  1. 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.

  2. In vitro antioxidant properties of the iron chelator pyridoxal isonicotinoyl hydrazone and some of its analogs.

    PubMed

    Schulman, H M; Hermes-Lima, M; Wang, E M; Ponka, P

    1995-11-01

    Since there are several problems with desferrioxamine (DFO) therapy, pyridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in iron-overload diseases. Iron chelation could also be helpful for experimental treatment of several other pathologies including rheumatoid arthritis and heart ischemia/reperfusion, due to the generation of oxyradicals and lipid peroxidation mediated by delocalized iron. We demonstrate here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA/ascorbate-mediated formation of hydroxyl-like radicals as tested by the release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay) and the formation of malonaldehyde from 2-deoxyribose damage. PIH could also decrease the rates of Fe(III)-EDTA-mediated oxidation of ascorbate and block the peroxidation of liposomes of rat brain phospholipids induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs-including salicylaldehyde isonicotinoyl hydrazone-and to DFO. We conclude that PIH and its analogs are effective new candidates against iron-mediated oxidative stress for use in experimental medicine. PMID:27405837

  3. Flavonoids induce HIF-1alpha but impair its nuclear accumulation and activity.

    PubMed

    Triantafyllou, Anastasia; Mylonis, Ilias; Simos, George; Bonanou, Sophia; Tsakalof, Andreas

    2008-02-15

    Hypoxia-inducible factor-1alpha (HIF-1alpha) is the regulatory subunit of the transcription factor HIF-1, which is highly involved in the pathology of diseases associated with tissue hypoxia. In this study we investigated the ability of plant flavonoids to induce HIF-1alpha and regulate HIF-1 transcriptional activity in HeLa cells. We demonstrate for the first time that the flavonoids baicalein, luteolin and fisetin, as well as the previously investigated quercetin, induce HIF-1alpha under normal oxygen pressure, whereas kaempferol, taxifolin, and rutin are inactive. We further reveal that the capability of flavonoids to bind efficiently intracellular iron and their lipophilicity are essential for HIF-1alpha induction. Despite the ability of flavonoids to stabilize HIF-1alpha, the transcriptional activity of HIF-1 induced by flavonoids was significantly lower than that observed with the iron chelator and known HIF-1 inducer, desferrioxamine (DFO). Furthermore, when cells in which HIF-1 had been induced by DFO were also treated with flavonoids, the transcriptional activity of HIF-1 was strongly impaired without simultaneous reduction in HIF-1alpha protein levels. Localization of HIF-1alpha by immuno- and direct fluorescence microscopy and in vitro phosphorylation assays suggest that flavonoids inhibit HIF-1 activity by impairing the MAPK-dependent phosphorylation of HIF-1alpha, thereby decreasing its nuclear accumulation.

  4. 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.

  5. 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.

  6. Mathilda (Matty) Bushel Canter (1924-2015).

    PubMed

    Matthews, Janet R

    2015-09-01

    Mathilda (Matty) Bushel Canter, a lifelong contributor to professional psychology, with a remarkable history of service, died in Phoenix, Arizona, on January 30, 2015. Matty was born in Brooklyn, New York, on June 8, 1924, the daughter of Harry and Bertha Bushel. She was preceded in death by her husband and fellow psychologist, Aaron Herman Canter in 1995. She and Aaron had two children, Rachelle (Shelley) and Steven. She is also survived by her brother Arthur Bushel of Baltimore. She made significant contributions to the profession on both a state and national level. Her contributions to the profession led to her being named a fellow of seven divisions of the American Psychological Association (APA; Divisions 12, 29, 31, 35, 42, 44, and 55). In 1984, she became the first female president of the APA Division of Psychotherapy (Division 29). In addition, she produced many articles for the media on the role of psychology in the community. Matty was a strong supporter of the American Psychological Foundation (APF). Matty received numerous awards from APA and its divisions for her contributions. She was a strong supporter of advocacy efforts in psychology and participated in numerous advocacy fundraising events. Her gentle way of handling tough situations earned nothing but respect. Matty mentored so many students and professionals, they are too numerous to note. A true giant of our profession has departed. PMID:26348338

  7. 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.

  8. 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.

  9. Serum and tissue selenium contents related to renal disease and colon cancer as determined by electrothermal atomic absorption spectrometry.

    PubMed

    Marchante-Gayón, J M; Sánchez-Uría, J E; Sanz-Medel, A

    1996-12-01

    Microwave digestion with nitric acid and hydrogen peroxide was applied to the determination of selenium in biological tissues by Electrothermal Atomic Absorption Spectrometry (ETAAS). Validation of this method is presented in terms of adequate recovery of selenium from standard reference materials and the method is applied to carcinogen human colon tissue. Ultramicrofiltration was used to study selenium protein binding and its fractionation and speciation in blood serum. These studies showed that 95% of the total selenium in serum seems to be bonded to high-molecular-weight proteins. Experiments with renal failure patients showed lower selenium levels than in the health population (0.57 +/- 0.23 mM versus 0.81 +/- 0.11 mM). A wider distribution pattern of total serum selenium concentration (from 0.1 to 1 mM) was clearly observed in renal failure patients. However, the ultramicrofiltrable selenium fraction was always constant, even in the presence of desferrioxamine (DFO).

  10. Multidentate terephthalamidate and hydroxypyridonate ligands: towards new orally active chelators.

    PubMed

    Abergel, Rebecca J; Raymond, Kenneth N

    2011-01-01

    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 (59)Fe, (238)Pu, and (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. PMID:21599440

  11. A framework for optimization and quantification of uncertainty and sensitivity for developing carbon capture systems

    DOE PAGES

    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 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Successful treatment of severe iron intoxication with gastrointestinal decontamination, deferoxamine, and hemodialysis.

    PubMed

    Gumber, Manoj R; Kute, Vivek B; Shah, Pankaj R; Vanikar, Aruna V; Patel, Himanshu V; Balwani, Manish R; Ghuge, Pramod P; Trivedi, Hargovind L

    2013-01-01

    Acute iron poisoning is a common and potentially serious problem in the pediatric population. Early recognition and treatment is crucial for a better outcome and to prevent morbidity and mortality. An 18-year-old female, who had accidental ingestion of 50 tablets of ferrous sulfate (100 mg of elemental iron per 335 mg tablet), 100 mg/kg of elemental iron, developed acute gastrointestinal and neurologic signs of toxicity and severe anion gap metabolic acidosis. The patient had received gastrointestinal decontamination, deferoxamine (DFO) infusion, and hemodialysis (HD) resulting in a decrease in serum iron concentration from 2150 to 160 mcg/dL at 24-h post-ingestion and improved mental status. Our cases demonstrate that HD may assist in decreasing serum iron concentration and improving clinical status in patients with massive overdose and life-threatening toxicity. PMID:23635030

  17. Recovery of DNA and fingerprints from touched documents.

    PubMed

    Sewell, Jonathan; Quinones, Ignacio; Ames, Carole; Multaney, Bryan; Curtis, Stuart; Seeboruth, Haj; Moore, Stephen; Daniel, Barbara

    2008-09-01

    This study investigated the various factors affecting DNA profiling from DNA recovered from fingerprints deposited on paper before and after fingerprint enhancement treatments. The DNeasy plant mini kit (QIAGEN) was found to improve DNA recovery from paper by over 150% compared with the QIAamp mini kit. A significant decrease in the amount of DNA recovered was observed following treatment with DFO and/or Ninhydrin. This decrease in yield did not have a comparably significant effect on the quality of the SGM Plus profiles. Furthermore, this study found that whilst certain paper types, such as newspaper, magazine and filter paper allowed for the good recovery of DNA, common office paper and white card, strongly interfered with the recovery of DNA resulting in poor quality profiles. PMID:19083837

  18. Oxidative stress induced by arsenopyrite and the role of desferrioxamine-B as radical scavenger.

    PubMed

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Gomez-Vidales, Virginia; Ramírez-Apán, María Teresa

    2013-02-01

    Arsenopyrite (FeAsS) is one of the earth's primary mineral sources of As, yet its effects on cell damage remain largely unknown. This paper addresses the question whether FeAsS induces lipid peroxidation (LP), a major indicator of oxidative stress. Screening and monitoring of LP was conducted using Thiobarbituric Acid Reactive Substances (TBARSs) assay. The lipid source was supernatant of rat brain homogenates. The formation of TBARS by FeAsS was rapid and took place just after 10 min. Maximum TBARS levels (ca. 14 nmol TBARS per mg of protein) were observed after 1h and remained constant thereafter. Suspension fraction separations showed that dissolved and structural components contributed to LP. The formation of TBARS by soluble As, As(III) or As(V), compared to basal levels. The initiation of LP by FeAsS was consistent with a mechanism initiated by the Fe(3+)/O(2)(-) redox system, and differed initiated by Fe(2+)/O(2). The effectiveness of FeAsS and FeSO(4) as inducer compared, and surpassed that of AAPH. On the other hand, the initiation of LP by FeAsS is consistent with a mechanism initiated by perferryl ion and Fe(3+)/O(2)(-), and differs from the mechanism characteristic of FeSO(4) initiated by the Fe(2+)/O(2) redox system. Proposedly, FeAsS surfaces contain a mixture of Fe(3+) and Fe(2+) that, along with O(2) and O(2)(-), participate in multiple mechanisms of electron transfer. EPR determinations show decreases in DMPO-OH adduct signal in FeAsS suspensions after adding desferrioxamine-B (DFO-B), consistent with the idea that DFO-B serves as a radical scavenger.

  19. Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

    PubMed

    Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

    2016-10-01

    Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. PMID:27474467

  20. 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

  1. 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.

  2. Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.

    PubMed

    Hamilton, Jasmine L; Hatef, Azadeh; Imran ul-Haq, Muhammad; Nair, Neelima; Unniappan, Suraj; Kizhakkedathu, Jayachandran N

    2014-01-01

    Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity.

  3. 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. PMID:26945724

  4. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.

    PubMed

    Aydinok, Yesim; 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

    2015-06-18

    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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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. PMID:2019018

  10. 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.

  11. Iron depletion increases manganese uptake and potentiates apoptosis through ER stress.

    PubMed

    Seo, Young Ah; Li, Yuan; Wessling-Resnick, Marianne

    2013-09-01

    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 60mg 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

  12. 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

  13. Reactive Oxygen Species are involved in BMP-Induced Dendritic Growth in Cultured Rat Sympathetic Neurons

    PubMed Central

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J.

    2015-01-01

    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 three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguiaretic 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. PMID:26079955

  14. Clinically Approved Iron Chelators Influence Zebrafish Mortality, Hatching Morphology and Cardiac Function

    PubMed Central

    Hamilton, Jasmine L.; Hatef, Azadeh; Imran ul-haq, Muhammad; Nair, Neelima; Unniappan, Suraj; Kizhakkedathu, Jayachandran N.

    2014-01-01

    Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity. PMID:25329065

  15. The Eltrombopag antitumor effect on hepatocellular carcinoma.

    PubMed

    Kurokawa, Tomohiro; Murata, Soichiro; Zheng, Yun-Wen; Iwasaki, Kenichi; Kohno, Keisuke; Fukunaga, Kiyoshi; Ohkohchi, Nobuhiro

    2015-11-01

    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

  16. 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

  17. 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. PMID:21882223

  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. Imaging the L-Type Amino Acid Transporter-1 (LAT1) with Zr-89 ImmunoPET

    PubMed Central

    Ikotun, Oluwatayo F.; Marquez, Bernadette V.; Huang, Chaofeng; Masuko, Kazue; Daiji, Miyamoto; Masuko, Takashi; McConathy, Jonathan; Lapi, Suzanne E.

    2013-01-01

    The L-type amino acid transporter-1 (LAT1, SLC7A5) is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine (FET) that are transport substrates for system L amino acid transporters including LAT1 have met limited success for oncologic imaging outside of the brain, and thus new strategies are needed for imaging LAT1 in systemic cancers. Here, we describe the development and biological evaluation of a novel zirconium-89 labeled antibody, [89Zr]DFO-Ab2, targeting the extracellular domain of LAT1 in a preclinical model of colorectal cancer. This tracer demonstrated specificity for LAT1 in vitro and in vivo with excellent tumor imaging properties in mice with xenograft tumors. PET imaging studies showed high tumor uptake, with optimal tumor-to-non target contrast achieved at 7 days post administration. Biodistribution studies demonstrated tumor uptake of 10.5 ± 1.8 percent injected dose per gram (%ID/g) at 7 days with a tumor to muscle ratio of 13 to 1. In contrast, the peak tumor uptake of the radiolabeled amino acid [18F]FET was 4.4 ± 0.5 %ID/g at 30 min after injection with a tumor to muscle ratio of 1.4 to 1. Blocking studies with unlabeled anti-LAT1 antibody demonstrated a 55% reduction of [89Zr]DFO-Ab2 accumulation in the tumor at 7 days. These results are the first report of direct PET imaging of LAT1 and demonstrate the potential of immunoPET agents for imaging specific amino acid transporters. PMID:24143237

  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. [The 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation].

    PubMed

    Neefjes, J; Groothuis, T A M; Dantuma, N P

    2004-12-25

    This year's Nobel Prize in Chemistry has been awarded to Aaron Ciechanover, Avram Herskho and Irwin Rose for the discovery of ubiquitin-mediated protein degradation. In a series of groundbreaking experiments these scientists described the basic principles for a unique posttranslational modification based on the conjugation of the small protein ubiquitin to proteins deemed for degradation. Although ubiquitin started in 1980 as an unusual modification of certain proteins, it is now clear that it functions as a signal for degradation when it forms a polymer. Hundreds of proteins are involved in the controlled destruction of ubiquitin-labelled proteins in the cell. And hundreds of other proteins are involved in protein modification by mono-ubiquitin, so that other processes, such as the formation of another degradation compartment, the lysosome, can proceed normally.

  2. 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. PMID:25032236

  3. 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.

  4. 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.

  5. Social network analysis for program implementation.

    PubMed

    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.

  6. 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.

  7. Beyond Depression: Towards a Process-Based Approach to Research, Diagnosis, and Treatment

    PubMed Central

    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.

    2012-01-01

    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. PMID:22509072

  8. 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.

  9. A theoretical framework for psychiatric nursing practice.

    PubMed

    Onega, L L

    1991-01-01

    Traditionally, specific theoretical frameworks which are congruent with psychiatric nursing practice have been poorly articulated. The purpose of this paper is to identify and discuss a philosophical base, a theoretical framework, application to psychiatric nursing, and issues related to psychiatric nursing knowledge development and practice. A philosophical framework that is likely to be congruent with psychiatric nursing, which is based on the nature of human beings, health, psychiatric nursing and reality, is identified. Aaron Antonovsky's Salutogenic Model is discussed and applied to psychiatric nursing. This model provides a helpful way for psychiatric nurses to organize their thinking processes and ultimately improve the health care services that they offer to their clients. Goal setting and nursing interventions using this model are discussed. Additionally, application of the use of Antonovsky's model is made to nursing research areas such as hardiness, uncertainty, suffering, empathy and literary works. Finally, specific issues related to psychiatric nursing are addressed.

  10. The beginnings of German governmental sponsorship in astronomy: the solar eclipse expeditions of 1868 as a prelude to the Venus transit expeditions of 1874 and 1882

    NASA Astrophysics Data System (ADS)

    Duerbeck, Hilmar W.

    The origins of the North German expeditions to observe the total solar eclipse of August 18, 1868, are outlined. The incentive was made by politician and science writer Aaron Bernstein, the financing was provided by the North German Federation, and the project was handled by members of the Astronomische Gesellschaft. The astronomical expeditions to Mulwar in India and Aden in South Arabia are summarized, the following archaeological expedition to upper Egypt is also considered. The activities of the participating scientists, also with respect to the preparation of popular accounts, are described. Finally, the impact of these expeditions on the planning of the large-scale project to observe the Venus transits of 1874 and 1882 is investigated.

  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. Reaction efficiency of diffusion-controlled processes on finite aperiodic planar arrays. II. Potential effects

    NASA Astrophysics Data System (ADS)

    Garza-López, Roberto A.; Brzezinski, Jack; Low, Daniel; Gomez, Ulysses; Raju, Swaroop; Ramirez, Craig; Kozak, John J.

    2009-08-01

    We continue our study of diffusion-reaction processes on finite aperiodic lattices, viz., the Penrose lattice and a Girih tiling. Focusing on bimolecular reactions, we mobilize the theory of finite Markov processes to document the effect of attractive forces on the reaction efficiency. Considering both a short-range square-well potential and a longer-range 1/ r S ( S = 4, 6) potential, we find that irreversible reactive encounters between reactants on a Girih platelet are kinetically advantaged relative to processes on a Penrose platelet. This result generalizes the conclusion reached in our earlier study [Roberto A. Garza-López, Aaron Kaufman, Reena Patel, Joseph Chang, Jack Brzezinski, John J. Kozak, Chem. Phys. Lett. 459 (2008) 137] where entropic factors (only) were assessed.

  13. Bilayer Graphene: An Electrically Tunable Semiconductor

    NASA Astrophysics Data System (ADS)

    Min, Hongki; Sahu, Bhagawan; Banerjee, Sanjay; MacDonald, Allan

    2007-03-01

    Using ab initio density functional theory calculations, we verify [1,2] that the energy band structure of bilayer graphene can be tuned by applying an external electric field. As the strength of the external electric field increases, the electronic spectrum of bilayer graphene changes from a that of a zero-gap semiconductor to that of a gapped semiconductor. From the ab initio calculations the external field dependence of the screened interlayer potential difference and tunneling amplitudes are extracted by fitting to a tight-binding model. We discuss the role of interlayer correlations in determining the size of the gap and the accuracy of local density approximation. [1] Edward McCann and Vladimir I. Fal'ko, Phys. Rev. Lett. 96, 086805 (2006). [2] Taisuke Ohta, Aaron Bostwick,, Thomas Seyller, Karsten Horn, and Eli Rotenberg, Science 313, 951 (2006).

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. Federally Qualified Health Centers Minimize the Impact of Loss of Frequency and Independence of Movement in Older Adult Patients through Access to Transportation Services

    PubMed Central

    Knight, Krystal Elaine

    2011-01-01

    Loss of mobility in older adults (65 and older) is associated with falling, loss of independence, and mortality. This paper, which to the author's knowledge is the first of its kind, summarizes findings of Federally Qualified Health Center (FQHC) case reports and how FQHCs minimize the impacts of mobility loss in older adult patients (who would not receive primary services without these transportation programs) by providing access to primary care services through transportation programs. This paper features the transportation programs of four FQHCs located in both urban and rural United States areas: LifeLong Medical Care (Oakland, CA); Hudson Headwaters Health Network (Queensbury, NY); North End Community Health Center (Boston, MA); Aaron E. Henry Community Health Services Center, Inc. (Clarksdale, MS). This paper is beneficial to primary care providers and public health officials in outlining how transportation may be used to minimize the effects of mobility loss in older adult patients. PMID:21748013

  1. 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

  2. Satisfaction with Counseling among Black Males in Transition from the Foster Care System

    PubMed Central

    Scott, Lionel D.; Munson, Michelle R.; White, Tony

    2009-01-01

    Using the Multidimensional Adolescent Satisfaction Scale (Garland, Saltzman, & Aarons, 2000), satisfaction with counseling and associated variables were examined among Black males (n = 47) transitioning from the foster care system. Potential associated variables assessed were foster care custody status, counseling status, diagnosis of major depression and disruptive behavior disorder based DSM-IV criteria, history of placement in congregate care settings, attitudes toward mental health services, stigma beliefs, and masculine norms. Results from simultaneous multiple regression analysis showed that attitudes toward mental health services contributed significantly to satisfaction with counseling. Specifically, Black males who expressed more positive attitudes toward mental health services in terms of confidence in mental health professionals and the therapeutic process reported greater satisfaction. Implications and future research directions are discussed. PMID:20046996

  3. Measurement of growing dynamical length scale on approach to jamming in granular systems

    NASA Astrophysics Data System (ADS)

    Durian, Douglas

    2009-03-01

    The flow of granular materials is of widespread practical and fundamental interest. One challenge to understanding and controlling behavior is that the response is nonlinear, with a forcing threshold below which the medium is static. Furthermore, just above threshold the response may be intermittent even though the forcing is steady. Two familiar examples are avalanches on a heap and clogging in a silo. Another example is dynamical heterogeneities for systems brought close to jamming, where intermediate-time motion is correlated in the form of intermitted string-like swirls. Here this will be illustrated with experiments on air-driven beads, where jamming is approached by lowering the effective temperature, as well as by experiments on rapid heap flow, where jamming is approached as a function of depth from the free surface. Use of novel statistical quantities and optical spectroscopies reveal a growing dynamical length scale on approach to jamming. Collaborators: Adam Abate, Hiroaki Katsuragi, Aaron Keys, Sharon Glotzer.

  4. 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.

  5. NASA DEVELOP students

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA DEVELOP students at Stennis Space Center recently held a midterm review with George Crozier, who serves as a science adviser to the team. The team also was joined by Jamie Favors of the Mobile (Ala.) County Health Department DEVELOP Team; Cheri Miller, the team's NASA adviser; and Kenton Ross, a team science adviser. Students participating in the meeting included: Lauren Childs, Jason Jones, Maddie Brozen, Matt Batina, Jenn Frey, Angie Maki and Aaron Brooks. The primary purpose of the meeting was to update Crozier on the status of the team's work for the summer 2008 term and discuss plans for the fiscal year 2009 project proposal. This included discussion of a possible project to study the effects of hurricanes on the Florida panhandle. DEVELOP is a NASA-sponsored, student-led, student-run program focused on developing projects to help communities.

  6. Adolescence: booze, brains, and behavior.

    PubMed

    Monti, Peter M; Miranda, Robert; Nixon, Kimberly; Sher, Kenneth J; Swartzwelder, H Scott; Tapert, Susan F; White, Aaron; Crews, Fulton T

    2005-02-01

    This article represents the proceedings of a symposium at the 2004 Research Society on Alcoholism meeting in Vancouver, British Columbia, Canada, organized and chaired by Peter M. Monti and Fulton T. Crews. The presentations and presenters were (1) Introduction, by Peter M. Monti; (2) Adolescent Binge Drinking Causes Life-Long Changes in Brain, by Fulton T. Crews and Kim Nixon; (3) Functional Neuroimaging Studies in Human Adolescent Drinkers, by Susan F. Tapert; (4) Abnormal Emotional Reactivity as a Risk Factor for Alcoholism, by Robert Miranda, Jr.; (5) Alcohol-Induced Memory Impairments, Including Blackouts, and the Changing Adolescent Brain, by Aaron M. White and H. Scott Swartzwelder; and (6) Discussion, by Kenneth Sher. PMID:15714044

  7. In Guanine We Trust: Genetic Testing and the Sense of Coherence.

    PubMed

    DuBois, James M; Antes, Alison L

    2015-01-01

    Aaron Antonovsky, the medical sociologist, defined the sense of coherence as a pervasive sense that the events in one's life are comprehensible, manageable, and meaningful or worthwhile. Research on the sense of coherence indicates that it is positively correlated with resilience and adaptive coping with disabilities and illnesses. The collection of first-person narratives published in Narrative Inquiry in Bioethics on genetic testing can be understood as expressions of the human effort to restore or sustain a sense of coherence in the face of illness, uncertainty, or even curiosity about one's origins and future wellbeing. While the medical usefulness of the genetic testing that was discussed in the collection of narratives was often modest, the contribution of testing to the sense of coherence was often greater. Understanding the sense of coherence as a possible motive for genetic testing might reshape the way that we conceive of the benefits and the burdens of genetic testing and the disclosure of incidental findings.

  8. 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.

  9. Definitions of the off-shell relative momentum in relativistic theories

    NASA Astrophysics Data System (ADS)

    Giebink, David R.

    1982-04-01

    A variety of definitions of the relative momentum in off-shell systems are discussed and a set of basic requirements for these momenta are established. The off-mass-shell Wightman-Gårding four-momentum, which has been employed most recently by Morioka and Afnan, is shown to be ambiguously defined, and it is shown that the relative four-momentum that is suggested by the magic-vector prescription of Aaron, Amado, and Young should not be used in off-mass-shell systems because it and the total four-momentum do not constitute a complete set of variables for the two-body system. NUCLEAR REACTIONS Relativistic kinematics, relative momentum, Bethe-Salpeter equation, Blankenbecler-Sugar reductions.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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)

  15. Thermal development of latent fingermarks on porous surfaces--further observations and refinements.

    PubMed

    Song, Di Fei; Sommerville, Daniel; Brown, Adam G; Shimmon, Ronald G; Reedy, Brian J; Tahtouh, Mark

    2011-01-30

    In a further study of the thermal development of fingermarks on paper and similar surfaces, it is demonstrated that direct contact heating of the substrate using coated or ceramic surfaces at temperatures in excess of 230°C produces results superior to those obtained using hot air. Fingermarks can also be developed in this way on other cellulose-based substrates such as wood and cotton fabric, though ridge detail is difficult to obtain in the latter case. Fluorescence spectroscopy indicates that the phenomena observed during the thermal development of fingermarks can be reproduced simply by heating untreated white copy paper or filter paper, or these papers treated with solutions of sodium chloride or alanine. There is no evidence to suggest that the observed fluorescence of fingermarks heated on paper is due to a reaction of fingermark constituents on or with the paper. Instead, we maintain that the ridge contrast observed first as fluorescence, and later as brown charring, is simply an acceleration of the thermal degradation of the paper. Thermal degradation of cellulose, a major constituent of paper and wood, is known to give rise to a fluorescent product if sufficient oxygen is available [1-5]. However, the absence of atmospheric oxygen has only a slight effect on the thermal development of fingermarks, indicating that there is sufficient oxygen already present in paper to allow the formation of the fluorescent and charred products. In a depletion study comparing thermal development of fingermarks on paper with development using ninhydrin, the thermal technique was found to be as sensitive as ninhydrin for six out of seven donors. When thermal development was used in sequence with ninhydrin and DFO, it was found that only fingermarks that had been developed to the fluorescent stage (a few seconds of heating) could subsequently be developed with the other reagents. In the reverse sequence, no useful further development was noted for fingermarks that were

  16. 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

  17. Assessing the role of chemical components in cellular responses to atmospheric particle matter (PM) through chemical fractionation of PM extracts.

    PubMed

    Heo, Jongbae; Antkiewicz, Dagmara S; Shafer, Martin M; Perkins, Dawn A K; Sioutas, Constantinos; Schauer, James J

    2015-08-01

    In order to further our understanding of the influence of chemical components and ultimately specific sources of atmospheric particulate matter (PM) on pro-inflammatory and other adverse cellular responses, we promulgate and apply a suite of chemical fractionation tools to aqueous aerosol extracts of PM samples for analysis in toxicity assays. We illustrate the approach with a study that used water extracts of quasi-ultrafine PM (PM0.25) collected in the Los Angeles Basin. Filtered PM extracts were fractionated using Chelex, a weak anion exchanger diethylaminoethyl (DEAE), a strong anion exchanger (SAX), and a hydrophobic C18 resin, as well as by desferrioxamine (DFO) complexation that binds iron. The fractionated extracts were then analyzed using high-resolution sector field inductively coupled plasma mass spectrometry (SF-ICPMS) to determine elemental composition. Cellular responses to the fractionated extracts were probed in an in vitro rat alveolar macrophages model with measurement of reactive oxygen species (ROS) production and the cytokine tumor necrosis factor-α (TNF-α). The DFO treatment that chelates iron was very effective at reducing the cellular ROS activity but had only a small impact on the TNF-α production. In contrast, the hydrophobic C18 resin treatment had a small impact on the cellular ROS activity but significantly reduced the TNF-α production. The use of statistical methods to integrate the results across all treatments led to the conclusion that sufficient iron must be present to participate in the chemistry needed for ROS activity, but the amount of ROS activity is not proportional to the iron solution concentration. ROS activity was found to be most related to cationic mono- and divalent metals (i.e., Mn and Ni) and oxyanions (i.e., Mo and V). Although the TNF-α production was not significantly affected by the chelexation of iron, it was greatly impacted by the removal of organics with the C18 resin and all other metal removal methods

  18. 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

    2010-01-01

    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

  19. Cerenkov luminescence imaging of medical isotopes

    PubMed Central

    Ruggiero, Alessandro; Holland, Jason P.; Lewis, Jason S.; Grimm, Jan

    2011-01-01

    The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies. Methods In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters 18F, 64Cu, 89Zr, and 124I; β-emitter 131I; and α-particle emitter 225Ac for potential use in CLI. The novel radiolabeled monoclonal antibody 89Zr-desferrioxamine B-[DFO-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies. Results Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-,β-, and α-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of 89Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities. Conclusion These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear

  20. 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

  1. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy

    PubMed Central

    Soliman, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo

    2014-01-01

    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation. Aims To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level. Methods Only BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM. Results DFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions Some impairment of liver function can occur

  2. Introduction and Mission Response Team (MRT)

    NASA Technical Reports Server (NTRS)

    Pool, Sam

    2005-01-01

    On February 1, 2003 the Space Shuttle Columbia, returning to Earth with a crew of seven astronauts, disintegrated along a track extending from California to Louisiana. Observers on the ground filmed breakup of the spacecraft. Debris fell along a 567 statute mile track from Littlefield, Texas to Fort Polk, Louisiana; the largest ever recorded debris field. At the time of the accident the National Aeronautics and Space Administration (NASA) flight surgeon on-duty at the Mission Control Center (MCC) in Houston, Texas initiated the medical contingency response. The DOD surgeon at Patrick Air Force Base was notified, NASA medical personnel were recalled and the services of Armed Forces Institute of Pathology (AFIP) were requested. Subsequent to the accident the NASA flight surgeons that had supported the crew on orbit now provided medical support to the crewmember s families. Federal Emergency Management Agency (FEMA), the National Transportation Safety Board (NTSB), the Federal Bureau of Investigation (FBI) and numerous other federal, state and local agencies along with the citizens of Texas and Louisiana responded to the disaster. Search and recovery was managed from a Disaster Field Office (DFO) established in Lufkin, Texas. Mishap Investigation Team (MIT) medical operations were managed from Barksdale Air Force Base, Louisiana. Accident investigation teams (Columbia Accident Investigation Task Force (CAITF) and Columbia Accident Investigation Board (CAIB)) appointed immediately after the disaster included current and former authorities in space medicine. In August 2003, the CAIB concluded its investigation and released its findings in a report published in February 2004.

  3. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells

    PubMed Central

    Guan, Longfei; Rui, Wei; Bai, Ru; Zhang, Wei; Zhang, Fang; Ding, Wenjun

    2016-01-01

    The aim of the present study was to investigate the effects of size-fractionated (i.e., <1; 1–2.5, and 2.5–10 µm in an aerodynamic diameter) ambient particulate matter (PM) on reactive oxygen species (ROS) activity and cell viability in human bronchial epithelial cells (BEAS-2B). The PM samples were collected from an urban site (uPM) in Beijing and a steel factory site (sPM) in Anshan, China, from March 2013 to December 2014. Metal elements, organic and elemental carbon, and water-soluble inorganic ions in the uPM and sPM were analyzed. The cell viability and ROS generation in PM-exposed BEAS-2B cells were measured by MTS and DCFH-DA. The results showed that both uPM and sPM caused a decrease in the cell viability and an increase in ROS generation. The level of ROS measured in sPM1.0 was approximately triple that in uPM1.0. The results of correlation analysis showed that the ROS activity and cytotoxicity were related to different PM composition. Moreover, deferoxamine (DFO) significantly prevented the increase of ROS generation and the decrease of cell viability. Taken together, our results suggest that the metals absorbed on PM induced oxidant radical generation in BEAS-2B cells that could lead to impairment of pulmonary function. PMID:27171105

  4. Involvement of DMT1 +IRE in the transport of lead in an in vitro BBB model.

    PubMed

    Wang, Qiang; Luo, Wenjing; Zhang, Wenbin; Liu, Mingchao; Song, Haifeng; Chen, Jingyuan

    2011-06-01

    Homeostasis of the central nervous system (CNS) microenvironment is maintained by the blood-brain barrier (BBB). The BBB is particularly vulnerable to lead (Pb) insults. This study was designed to test the hypothesis that divalent metal transporter 1 (DMT1), which is a divalent cation membrane transporter, was involved in transcellular transport across the BBB. An in vitro BBB model, which was a co-culture system of human umbilical vascular endothelial cells (ECV304) and rat glioma cells (C6), was established. Transendothelial electrical resistance (TEER) and fluoresceinisothiocyanate (FITC)-dextran permeability results showed that Pb exposure at the tested concentrations had no significant effects on intercellular tightness. Pb transport displayed properties that were associated with iron response element (IRE) positive isoform of DMT1. Accordingly, Pb transport was significantly blocked by iron (Fe). Moreover, ECV304 cells that were depleted of Fe with the chelator deferoxamine (DFO) demonstrated increased Pb transport. By transfecting ECV-304 cells with a DMT1 expression vector, overexpression of DMT1 promoted an increase in Pb transport. Treatment of ECV304 cells with DMT1 antisense oligonucleotides (ASONs) MA1 significantly inhibited the transport of Pb. Our results suggest that Pb is transported in the in vitro BBB model by a transporter with biochemical properties similar to those of the DMT1 IRE-positive isoform.

  5. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo

    PubMed Central

    Lee, Jehn-Chuan; Chiang, Kun-Chun; Feng, Tsui-Hsia; Chen, Yu-Jen; Chuang, Sung-Ting; Tsui, Ke-Hung; Chung, Li-Chuan; Juang, Horng-Heng

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment. PMID:27589737

  6. Automated Ground Umbilical Systems (AGUS) Project

    NASA Technical Reports Server (NTRS)

    Gosselin, Armand M.

    2007-01-01

    All space vehicles require ground umbilical systems for servicing. Servicing requirements can include, but are not limited to, electrical power and control, propellant loading and venting, pneumatic system supply, hazard gas detection and purging as well as systems checkout capabilities. Of the various types of umbilicals, all require several common subsystems. These typically include an alignment system, mating and locking system, fluid connectors, electrical connectors and control !checkout systems. These systems have been designed to various levels of detail based on the needs for manual and/or automation requirements. The Automated Ground Umbilical Systems (AGUS) project is a multi-phase initiative to develop design performance requirements and concepts for launch system umbilicals. The automation aspect minimizes operational time and labor in ground umbilical processing while maintaining reliability. This current phase of the project reviews the design, development, testing and operations of ground umbilicals built for the Saturn, Shuttle, X-33 and Atlas V programs. Based on the design and operations lessons learned from these systems, umbilicals can be optimized for specific applications. The product of this study is a document containing details of existing systems and requirements for future automated umbilical systems with emphasis on design-for-operations (DFO).

  7. Performance of 1,2-indanedione and the need for sequential treatment of fingerprints.

    PubMed

    Mangle, Milery Figuera; Xu, Xioama; de Puit, M

    2015-09-01

    The use of 1,2-indanedione-ZnCl2 (IND-Zn) for the visualisation of fingermarks on porous materials has been widely accepted. The use of the reagent in comparison with others has been well described. To what extent IND or IND-Zn reacts with amino acids, in comparison to ninhydrin, has not been described to date. In this technical note we describe the analysis of amino acids with LCMS with the purpose of understanding the reactivity of ninhydrin, IND-Zn and the sequence thereof. The consumption of amino acids by these visualisation reagents is a feature we propose to use for calculations on the reactivity of these reagents. By using recently developed methods for the quantification of amino acids, we determined the consumption of these entities by visualisation reagents. We show that the differences in reactivity between IND and ninhydrin are not as big as the differences between 1,8-diazafluoren-9-one (DFO) and ninhydrin. We also show that it is of great importance to use IND-Zn and ninhydrin in sequence, in order to fully consume the amino acids present in fingermarks. PMID:26385717

  8. Visualising substrate-fingermark interactions: Solid-state NMR spectroscopy of amino acid reagent development on cellulose substrates.

    PubMed

    Spindler, Xanthe; Shimmon, Ronald; Roux, Claude; Lennard, Chris

    2015-05-01

    Most spectroscopic studies of the reaction products formed by ninhydrin, 1,2-indanedione-zinc (Ind-Zn) and 1,8-diazafluoren-9-one (DFO) when reacted with amino acids or latent fingermarks on paper substrates are focused on visible absorption or luminescence spectroscopy. In addition, structural elucidation studies are typically limited to solution-based mass spectrometry or liquid nuclear magnetic resonance (NMR) spectroscopy, which does not provide an accurate representation of the fingermark development process on common paper substrates. The research presented in this article demonstrates that solid-state carbon-13 magic angle spinning NMR ((13)C-MAS-NMR) is a technique that can not only be utilised for structural studies of fingermark enhancement reagents, but is a promising technique for characterising the effect of paper chemistry on fingermark deposition and enhancement. The latter opens up a research area that has been under-explored to date but has the potential to improve our understanding of how fingermark secretions and enhancement reagents interact with paper substrates. PMID:25766739

  9. Assessment of the ability of seaweed extracts to protect against hydrogen peroxide and tert-butyl hydroperoxide induced cellular damage in Caco-2 cells.

    PubMed

    O'Sullivan, A M; O'Callaghan, Y C; O'Grady, M N; Queguineur, B; Hanniffy, D; Troy, D J; Kerry, J P; O'Brien, N M

    2012-09-15

    The ability of brown seaweed extracts, Ascophyllum nodosum, Laminaria hyperborea, Pelvetia canaliculata, Fucus vesiculosus and Fucus serratus to protect against tert-butyl hydroperoxide (tert-BOOH) induced stress in Caco-2 cells was investigated. Oxidative stress was determined by measuring alteration in the enzymatic activity of catalase (CAT) and superoxide dismutases (SOD) and cellular levels of glutathione (GSH). L. hyperborea, P. canaliculata and F. serratus significantly protected against tert-BOOH induced SOD reduction but did not protect against the reduction in CAT activity or the increased cellular levels of GSH. The ability of F. serratus and F. vesiculosus to protect against H(2)O(2) and tert-BOOH induced DNA damage was also assessed. The DNA protective effects of the two seaweed extracts was compared to those of three metal chelators; deferoxamine mesylate (DFO), 1,10-phenanthroline (o-phen) and 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (BAPTA-AM). F. serratus and F. vesiculosus significantly protected (P<0.05) against H(2)O(2) (50 μM) induced DNA damage but not tert-BOOH induced damage. PMID:23107739

  10. Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

    PubMed

    Santos, M A; Esteves, M A; Chaves, S

    2012-01-01

    This review is focused on recent developments on hydroxypyri(mi)dines, as aluminum and actinide chelating agents to combat the toxicity due to accumulations of these metal ions in human body resulting from excessive metal exposure. After a brief update revision of the most common processes of aluminum (Al) exposure, as well as the associated toxicities and pathologies, we will focus on the current available Al chelators and future perspective as potential antidotes of Al toxicity. Due to the similarity between Al and Fe, a major emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators, since they are analogues of the current iron chelators in clinical use (DFP and DFO). This review includes issues such as molecular design strategies and corresponding effects on the associated physico-chemical properties, lipo-hydrophilic balance, toxicity, in vivo bioassays and current clinical applications. The hydroxypyri(mi)dine chelators are also suitable for other hard metal ions, such as the radiotoxic actinides, and so a brief review is included on the applications of these chelators in actinides scavenging.

  11. Effective combination therapy of deferiprone and deferoxamine for the rapid clearance of excess cardiac IRON and the prevention of heart disease in thalassemia. The Protocol of the International Committee on Oral Chelators.

    PubMed

    Kolnagou, Annita; Kontoghiorghes, George J

    2006-01-01

    The International Committee on Oral Chelators (ICOC) combination therapy protocol involving the administration of deferiprone (L1) during the day (80-110 mg/kg/day) and deferoxamine (DFO) (40-60 mg/kg at least 3 days/week) during the night for 8-12 hours using a pump, or the whole 24 hours using an elastomeric pump infuser, has been tested in 11 thalassemia patients (seven males, four females) over a period of 9-28 months. The patients had variable serum ferritin levels (0.54-4.6 mg/L) and cardiac iron load ranging from normal to severe siderosis levels (MRI T2*: 4.7-45 ms). There was a substantial overall reduction in serum ferritin levels (0.17-2.16 mg/L) and normalization of cardiac iron (MRI T2* >20 ms) in all patients. In two patients with severe and moderate cardiac iron load range levels, cardiac iron normalization was achieved within 9-10 months. Two patients on L1 monotherapy (80-120 mg/kg/day) maintained normal range MRI T2* cardiac iron levels over the same period. The ICOC combination therapy protocol appears to be the most effective and least cumbersome form of chelation treatment for the rapid clearance of excess iron from the heart. PMID:16798649

  12. Amyloid β25-35 induced ROS-burst through NADPH oxidase is sensitive to iron chelation in microglial Bv2 cells.

    PubMed

    Part, Kristin; Künnis-Beres, Kai; Poska, Helen; Land, Tiit; Shimmo, Ruth; Zetterström Fernaeus, Sandra

    2015-12-10

    Iron chelation therapy and inhibition of glial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can both represent possible routes for Alzheimer's disease modifying therapies. The metal hypothesis is largely focused on direct binding of metals to the N-terminal hydrophilic 1-16 domain peptides of Amyloid beta (Aβ) and how they jointly give rise to reactive oxygen species (ROS) production. The cytotoxic effects of Aβ through ROS and metals are mainly studied in neuronal cells using full-length Aβ1-40/42 peptides. Here we study cellularly-derived ROS during 2-60min in response to non-metal associated mid domain Aβ25-35 in microglial Bv2 cells by fluorescence based spectroscopy. We analyze if Aβ25-35 induce ROS production through NADPH oxidase and if the production is sensitive to iron chelation. NADPH oxidase inhibitor diphenyliodonium (DPI) is used to confirm the production of ROS through NADPH oxidase. We modulate cellular iron homeostasis by applying cell permeable iron chelators desferrioxamine (DFO) and deferiprone (DFP). NADPH oxidase subunit gp91-phox level was analyzed by Western blotting. Our results show that Aβ25-35 induces strong ROS production through NADPH oxidase in Bv2 microglial cells. Intracellular iron depletion resulted in restrained Aβ25-35 induced ROS.

  13. Performance of 1,2-indanedione and the need for sequential treatment of fingerprints.

    PubMed

    Mangle, Milery Figuera; Xu, Xioama; de Puit, M

    2015-09-01

    The use of 1,2-indanedione-ZnCl2 (IND-Zn) for the visualisation of fingermarks on porous materials has been widely accepted. The use of the reagent in comparison with others has been well described. To what extent IND or IND-Zn reacts with amino acids, in comparison to ninhydrin, has not been described to date. In this technical note we describe the analysis of amino acids with LCMS with the purpose of understanding the reactivity of ninhydrin, IND-Zn and the sequence thereof. The consumption of amino acids by these visualisation reagents is a feature we propose to use for calculations on the reactivity of these reagents. By using recently developed methods for the quantification of amino acids, we determined the consumption of these entities by visualisation reagents. We show that the differences in reactivity between IND and ninhydrin are not as big as the differences between 1,8-diazafluoren-9-one (DFO) and ninhydrin. We also show that it is of great importance to use IND-Zn and ninhydrin in sequence, in order to fully consume the amino acids present in fingermarks.

  14. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial

    PubMed Central

    Porter, John; Bowden, Donald K.; Economou, Marina; Troncy, Jacques; Ganser, Arnold; Habr, Dany; Martin, Nicolas; Gater, Adam; Rofail, Diana; Abetz-Webb, Linda; Lau, Helen; Cappellini, Maria Domenica

    2012-01-01

    Treatment of iron overload using deferoxamine (DFO) is associated with significant deficits in patients' health-related quality of life (HRQOL) and low treatment satisfaction. The current article presents patient-reported HRQOL, satisfaction, adherence, and persistence data from β-thalassemia (n = 274) and myelodysplastic syndrome (MDS) patients (n = 168) patients participating in the Evaluation of Patients' Iron Chelation with Exjade (EPIC) study (NCT00171821); a large-scale 1-year, phase IIIb study investigating the efficacy and safety of the once-daily oral iron chelator, deferasirox. HRQOL and satisfaction, adherence, and persistence to iron chelation therapy (ICT) data were collected at baseline and end of study using the Medical Outcomes Short-Form 36-item Health Survey (SF-36v2) and the Satisfaction with ICT Questionnaire (SICT). Compared to age-matched norms, β-thalassemia and MDS patients reported lower SF-36 domain scores at baseline. Low levels of treatment satisfaction, adherence, and persistence were also observed. HRQOL improved following treatment with deferasirox, particularly among β-thalassemia patients. Furthermore, patients reported high levels of satisfaction with deferasirox at end of study and greater ICT adherence, and persistence. Findings suggest deferasirox improves HRQOL, treatment satisfaction, adherence, and persistence with ICT in β-thalassemia and MDS patients. Improving such outcomes is an important long-term goal for patients with iron overload. PMID:22924125

  15. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons

    PubMed Central

    Aguirre, Pabla; Mena, Natalia P.; Carrasco, Carlos M.; Muñoz, Yorka; Pérez-Henríquez, Patricio; Morales, Rodrigo A.; Cassels, Bruce K.; Méndez-Gálvez, Carolina; García-Beltrán, Olimpo; González-Billault, Christian; Núñez, Marco T.

    2015-01-01

    Neuronal death in Parkinson’s disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2’-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death. PMID:26658949

  16. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo.

    PubMed

    Lee, Jehn-Chuan; Chiang, Kun-Chun; Feng, Tsui-Hsia; Chen, Yu-Jen; Chuang, Sung-Ting; Tsui, Ke-Hung; Chung, Li-Chuan; Juang, Horng-Heng

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment. PMID:27589737

  17. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

    PubMed

    Aguirre, Pabla; Mena, Natalia P; Carrasco, Carlos M; Muñoz, Yorka; Pérez-Henríquez, Patricio; Morales, Rodrigo A; Cassels, Bruce K; Méndez-Gálvez, Carolina; García-Beltrán, Olimpo; González-Billault, Christian; Núñez, Marco T

    2015-01-01

    Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death. PMID:26658949

  18. Brain iron accumulation exacerbates the pathogenesis of MPTP-induced Parkinson's disease.

    PubMed

    You, L-H; Li, F; Wang, L; Zhao, S-E; Wang, S-M; Zhang, L-L; Zhang, L-H; Duan, X-L; Yu, P; Chang, Y-Z

    2015-01-22

    Brain iron levels are significantly increased in Parkinson's disease (PD) and iron deposition is observed in the substantia nigra (SN) of PD patients. It is unclear whether iron overload is an initial cause of dopaminergic neuronal death or merely a byproduct that occurs in the SN of PD patients. In this study, ceruloplasmin knockout (CP-/-) mice and mice receiving an intracerebroventricular injection of ferric ammonium citrate (FAC) were selected as mouse models with high levels of brain iron. These mice were administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by intraperitoneal injection. Their behavior and the dopaminergic neuron damage to their substantia nigra pars compacta (SNpc) were assessed. These findings suggest that the injection of FAC or the absence of the CP gene may exacerbate both the observed apoptosis of TH-positive neurons and the behavioral symptoms of the MPTP-treated mice. The intracerebroventricular injection of deferoxamine (DFO) significantly alleviated the neuronal damage caused by MPTP in CP-/- mice. Furthermore, our findings suggest that the increased nigral iron content exacerbates the oxidative stress levels, promoting apoptosis through the Bcl-2/Bax pathway and the activated caspase-3 pathway in the brain. Therefore, iron overload in the brain exacerbates dopaminergic neuronal death in SNpc and leads to the onset of PD. PMID:25301748

  19. Evidence for Hydroxamate Siderophores and Other N-Containing Organic Compounds Controlling (239,240)Pu Immobilization and Remobilization in a Wetland Sediment.

    PubMed

    Xu, Chen; Zhang, Saijin; Kaplan, Daniel I; Ho, Yi-Fang; Schwehr, Kathleen A; Roberts, Kimberly A; Chen, Hongmei; DiDonato, Nicole; Athon, Matthew; Hatcher, Patrick G; Santschi, Peter H

    2015-10-01

    Pu concentrations in wetland surface sediments collected downstream of a former nuclear processing facility in F-Area of the Savannah River Site (SRS), USA, were ∼2.5 times greater than those measured in the associated upland aquifer sediments; similarly, the Pu concentration solid/water ratios were orders of magnitude greater in the wetland than in the low-organic matter content aquifer soils. Sediment Pu concentrations were correlated to total organic carbon and total nitrogen contents and even more strongly to hydroxamate siderophore (HS) concentrations. The HS were detected in the particulate or colloidal phases of the sediments but not in the low molecular weight fractions (<1000 Da). Macromolecules which scavenged the majority of the potentially mobile Pu were further separated from the bulk mobile organic matter fraction ("water extract") via an isoelectric focusing experiment (IEF). An electrospray ionization Fourier-transform ion cyclotron resonance ultrahigh resolution mass spectrometry (ESI FTICR-MS) spectral comparison of the IEF extract and a siderophore standard (desferrioxamine; DFO) suggested the presence of HS functionalities in the IEF extract. This study suggests that while HS are a very minor component in the sediment particulate/colloidal fractions, their concentrations greatly exceed those of ambient Pu, and HS may play an especially important role in Pu immobilization/remobilization in wetland sediments.

  20. Concurrent expression of heme oxygenase-1 and p53 in human retinal pigment epithelial cell line

    SciTech Connect

    Lee, Sang Yull; Jo, Hong Jae; Kim, Kang Mi; Song, Ju Dong; Chung, Hun Taeg; Park, Young Chul

    2008-01-25

    Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate cellular functions such as cell proliferation, inflammation, and apoptosis. Here, we investigated the effects of HO activity on the expression of p53 in the human retinal pigment epithelium (RPE) cell line ARPE-19. Cobalt protoporphyrin (CoPP) induced the expression of both HO-1 and p53 without significant toxicity to the cells. In addition, the blockage of HO activity with the iron chelator DFO or with HO-1 siRNA inhibited the CoPP-induced expression of p53. Similarly, zinc protoporphyrin (ZnPP), an inhibitor of HO, suppressed p53 expression in ARPE-19 cells, although ZnPP increased the level of HO-1 protein while inhibiting HO activity. Also, CoPP-induced p53 expression was not affected by the formation of reactive oxygen species (ROS). Based on these results, we conclude that HO activity is involved in the regulation of p53 expression in a ROS-independent mechanism, and also suggest that the expression of p53 in ARPE-19 cells is associated with heme metabolites such as biliverdin/bilirubin, carbon monoxide, and iron produced by the activity of HO.